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A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1827-1844页

作者： Zinan Zhang Wenbin Cao Huanchun Xing Shuai Guo Lijuan Huang Lin Wang Xin Sui Kui Lu Yuan Luo Yongan Wang Jun Yang state key laboratory of toxicology and medical countermeasures Beijing Institutes of Pharmacology and ToxicologyBeijing 100850China Tianjin University of Science and Technology Tianjin 300222China Hebei University of Science and Technology Shijiazhuang 050018China

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be overcome.In this study,we propose a brain-targeted delivery strat-egy based on selective opening of the BBB.This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing through.Based on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain immediately.At an effective dose,this delivery system is safe,especially with its effect on the BBB being reversible.This mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

关键词： Liposomes Phospholipase A2 Phosphoserine Blood-brainbarrier Selectively open Mix&act

Targeting NRP1 axis as a strategy for treating energy metabolism impairment induced by SARS-CoV-2 spike

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Science China Life Sciences 2024年

作者： Lihui Zhang Wanting Hu Jingxuan Li Yuehan Li Feng Liu Wenyi Xiao Ning Jiang Zhiyong Xiao Lu Han Wenxia Zhou Beijing Institute of Pharmacology & toxicology state key laboratory of toxicology and medical countermeasures Beijing Institute of Pharmacology & Toxicology School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine

Dear Editor,Free spike protein of SARS-CoV-2 alone can cause abnormal energy metabolism(Table S1 in Supporting Information), and limited research suggested a potential correlation between spike-induced mitochondrial damage and the ACE2 receptor(Lei et al., 2021; Yang et al., 2023). In order to further explore the mechanisms involved, we observed that the wild-type S1 protein of SARS-CoV-2 exerts a more potent inhibitory effect on host cell ATP compared to the wild-type S protein, S2protein, the Omicron variant S1 protein and HCoV-NL63 S1protein in HLMVEC and 293T cell lines(Figure 1A and B),indicating the importance of exploring the mechanism by which the S1 protein causes ATP decrease. Meanwhile, the S1protein did not lead to significant changes in cellular lactate levels, indicating that its primary mechanism involves impairing oxidative phosphorylation and mitochondrial damage(Figure 1C and D).

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circRNAs deregulation in exosomes derived from BEAS-2B cells is associated with vascular stiffness induced by PM_(2.5)

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Journal of Environmental Sciences 2024年第3期137卷 527-539页

作者： Qingping Liu Yaling Zhang Bin Han Mengruo Wang Huaifang Hu Jie Ning Wentao Hu Meiyu Chen Yaxian Pang Yuanyuan Chen Lei Bao Yujie Niu Rong Zhang Department of toxicology Hebei Medical UniversityShijiazhuang 050017China state key laboratory of Environment Health(Incubation) Key Laboratory of Environment and HealthMinistry of EducationKey Laboratory of Environment and Health(Wuhan)Ministry of Environmental ProtectionSchool of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China China CDC key laboratory of Environment and Population Health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing 100021China Occupational Health and Environmental Health Hebei Medical UniversityShijiazhuang 050017China Hebei key laboratory of Environment and Human Health Hebei Medical UniversityShijiazhuang 050017China

As an environmental pollutant,ambient fine particulate matter (PM_(2.5)) was linked to cardiovascular diseases.The molecular mechanisms underlying PM_(2.5)-induced extrapulmonary disease has not been elucidated clearly.In this study the ambient PM_(2.5)exposure mice model we established was to explore adverse effects of vessel and potential mechanisms.Long-term PM_(2.5)exposure caused reduced lung function and vascular stiffness in mice.And chronic PM_(2.5)induced migration and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B cells.After PM_(2.5)treatment,the circRNAs and mRNAs levels of exosomes released by BEAS-2B cells were detected by competing endogenous RNA (ceRNA) array,which contained 1664 differentially expressed circRNAs (DE-circRNAs) and 308 differentially expressed m RNAs (DE-mRNAs).By bioinformatics analysis on host genes of DE-circRNAs,vascular diseases and some pathways related to vascular diseases including focal adhesion,tight junction and adherens junction were enriched.Then,ceRNA network was constructed,and DE-mRNAs in ceRNA network were conducted functional enrichment analysis by Ingenuity Pathway Analysis,which indicated that hsa_circ_0012627,hsa_circ_0053261and hsa_circ_0052810 were related to vascular endothelial dysfunction.Furthermore,it was verified experimentally that Exo^(PM2.5)could induce endothelial dysfunction by increased endothelial permeability and decreased relaxation in vitro.In present study,we investigated in-depth knowledge into the molecule events related to PM_(2.5) toxicity and pathogenesis of vascular diseases.

关键词： Fine particulate matter Vascular stiffness Exosome ceRNA microarray Endothelial dysfunction

CoFe_(2)O_(4) decorated graphene/C_(18)-functionalized mesoporous silica nanocomposites prepared for magnetic enrichment and electrochemical detection of promethazine in beef

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Chinese Chemical Letters 2024年第3期35卷 208-213页

作者： Xingdong Yang Shi-Ming Ying Sen Zhang Jinxia Dai Wei Gao Tian-Qi Wang Jun-Qin Qiao Hong-Zhen Lian Li Mao state key laboratory of Analytical Chemistry for Life Science School of Chemistry&Chemical Engineering and Centre of Materials AnalysisNanjing UniversityNanjing 210023China Ministry of Education(MOE)key laboratory of Modern toxicology School of Public HealthNanjing Medical UniversityNanjing 211166China

Promethazine(PHZ)is used as a sedative in veterinary medicine,and its residue can threaten the health of human.The electrochemical detection of PHZ is suitable method for application in the field.However,the traditional electroanalysis is difficult to perform directly in meat samples due to matrix interference.This work integrates magnetic solid-phase extraction and differential pulse voltammetry for highly sensitive and selective determination of PHZ in beef and beef liver for the first time.CoFe_(2)O_(4)/graphene coated with C_(18)-functionalized mesoporous silica(MG@mSiO_(2)-C_(18))is synthesized as dispersed magnetic adsorbent to extract PHZ.Magnetic glassy carbon electrode modified with nitrogen-doped hollow carbon microspheres(HCM)attracts the MG@mSiO_(2)-C_(18)with PHZ,and directly detects the PHZ without elution procedure.MG@mSiO_(2)-C_(18)can separate PHZ to avoid the interference of impurities on following detection,and also concentrate PHZ on magnetic electrode.Additionally,the electrode modification with HCM can amplify the electrochemical signal of PHZ.Finally,the integrated PHZ determination method exhibits a wide linear range from 0.08μmol/L to 300μmol/L with a low limit of detection of 9.8 nmol/L.The beef sample analysis presents excellent recovery,demonstrating that this protocol is promising for the rapid and onsite detection of PHZ in real meat samples。

关键词： Promethazine(PHZ) Drug residue Magnetic solid phase extraction Electrochemical detection Beef

Residential energy transition and chronic respiratory diseases

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The Innovation 2024年第3期5卷 33-43页

作者： Hongcheng Wei Qiurun Yu Danrong Chen Mingzhi Zhang Quanquan Guan Bo Hang Antoine M.Snijders Adrian Covaci Yankai Xia state key laboratory of Reproductive Medicine and Offspring Health Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China key laboratory of Modern toxicology of Ministry of Education School of Public HealthNanjing Medical UniversityNanjing 211166China The Affiliated Wuxi People’s Hospital of Nanjing medical University Wuxi People’s HospitalWuxi Medical CenterNanjing Medical UniversityWuxi 214023China Biological Systems and Engineering Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Toxicological Centre University of Antwerp2610 WilrijkBelgium

Obtaining clean energy is of prime importance for planetary health and sustainable development.We aimed to assess the association between residential energy transition and the risk of chronic respiratory diseases.Using data from the Global Health Observatory and Global Burden of Diseases,Injuries,and Risk Factors Study,we delineated the spatial distribution and temporal trends of the population using clean fuels for cooking at a global scale.In the China Health and Retirement Longitudinal Study,we performed rigorous and well-structured multistage analyses incorporating both cross-sectional and prospective data analyses to examine the associations between solid fuel use,residential energy transition,duration of solid fuel use,and the risk of chronic respiratory diseases.Despite great progress,huge disparities in access to clean energy persist globally.Residential energy transition was associated with a lower risk of chronic respiratory diseases.In the period of 2011–2013,compared with persistent solid fuel users,both participants who switched from solid to clean fuels(adjusted risk ratio[RR]0.78,95%confidence interval[CI]0.62–0.98)and persistent clean fuel users(adjusted RR 0.71,95%CI 0.57–0.89)had significantly lower risk of chronic respiratory diseases(p<0.001 for trend).Consistent associations were observed in the period of 2011–2015 and 2011–2018.Household energy transition from solid to clean fuels could reduce the risk of chronic respiratory diseases.This is a valuable lesson for policy-makers and the general public to accelerate energy switching to alleviate the burden of chronic respiratory diseases and achieve health benefits,particularly in low-and middle-income countries.

关键词： cooking income globally

Research on ozone formation sensitivity based on observational methods:Development history,methodology,and application and prospects in China

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Journal of Environmental Sciences 2024年第4期138卷 543-560页

作者： Wanghui Chu Hong Li Yuanyuan Ji Xin Zhang Likun Xue Jian Gao Cong An state key laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China Environment Research Institute Shandong UniversityQingdao 266237China

Observation-based method for O_(3)formation sensitivity research is an important tool to analyze the causes of ground-level O_(3)pollution,which has broad application potentials in determining the O_(3)pollution formation mechanism and developing prevention and control strategies.This paper outlined the development history of research on O_(3)formation sensitivity based on observational methods,described the principle and applicability of the methodology,summarized the relative application results in China and provided recommendations on the prevention and control of O_(3)pollution in China based on relevant study results,and finally pointed out the shortcomings and future development prospects in this field in China.The overview study showed that the O_(3)formation sensitivity in some urban areas in China in recent years presented a gradual shifting tendency from the VOC-limited regime to the transition regime or the NO_(x)-limited regime due to the implementation of the O_(3)precursors emission reduction policies;O_(3)pollution control strategies and precursor control countermeasures should be formulated based on local conditions and the dynamic control capability of O_(3)pollution control measures should be improved.There are still some current deficiencies in the study field in China.Therefore,it is recommended that a stereoscopic monitoring network for atmospheric photochemical components should be further constructed and improved;the atmospheric chemical mechanisms should be vigorously developed,and standardized methods for determining the O_(3)formation sensitivity should be established in China in the near future.

关键词： Observation-based method Ozone formation sensitivity Ozone pollution prevention and control VOCs NO_(x) OBM

Formulation,characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement

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Journal of Traditional Chinese Medicine 2024年第1期44卷 54-62页

作者： LI Xiuyan LUO Yuting WANG Jinhui DU Zhimin key laboratory of Basic and Application Research of Beiyao Heilongjiang University of Chinese MedicineMinistry of EducationHarbin 150040China College of Pharmacy Harbin Medical UniversityHarbin 150081China Institute of Clinical Pharmacology the Second Affliated Hospital of Harbin Medical University(University Key aboratory of Drug ResearchHeilongjiang Province)Harbin 150086China Department of Clinical Pharmacology College of Pharmacy Harbin Medical UniversityHarbin 150081China state key laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacao 999078China

OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in vivo.METHODS:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers.Thermogravimetric analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AESD.Optimal prescriptions were screened via the dissolution degree determination method.Using Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid dispersion.Acute toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for toxicity.RESULTS:AE-SD showed that AE existed in the carrier in an amorphous state.Compared with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion.Therefore,it was more suitable as a carrier material for AE-SD.The addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of PVP.The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also optimal.Based on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than AE.The results showed that the drug metabolism in AE-SD was better,and the residence time was shorter.The toxicology study showed that both AE and AE-SD had no toxicity.CONCLUSION:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,as demonstrated by in vitro dissolution experime

关键词： aloe-emodin solid dispersion solvent evaporation drug liberation pharmacokinetics

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 cells.The 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 cells.Due 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 targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,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

HvMPK4 phosphorylates HvWRKY1 to enhance its suppression of barley immunity to powdery mildew fungus

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Journal of Genetics and Genomics 2024年第3期51卷 313-325页

作者： Pengya Xue Ling Zhang Renchun Fan Yanan Li Xinyun Han Ting Qi Lifang Zhao Deshui Yu Qian-Hua Shen state key laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions College of Advanced Agricultural SciencesUniversity of Chinese Academy of SciencesBeijing 100049China Department of Nutritional Sciences&toxicology University of CaliforniaBerkeleyCA 94720USA Lushan Botanical Garden Chinese Academy of ScienceJiujiangJiangxi 332900China

Mitogen-activated protein kinase(MAPK)cascades play important roles in disease resistance in model plant species.However,the functions of MAPK signaling pathways in crop disease resistance are largely unknown.Here we report the function of HvMKK1-HvMPK4-HvWRKY1 module in barley immune system.HvMPK4 is identified to play a negative role in barley immune response against Bgh,as virus-induced gene silencing of HvMPK4 results in enhanced disease resistance whilst stably overexpressing HvMPK4 leads to super-susceptibility to Bgh infection.Furthermore,the barley MAPK kinase HvMKK1 is found to specifically interact with HvMPK4,and the activated HvMKK1^(DD) variant specifically phosphorylates HvMPK4 in vitro.Moreover,the transcription factor HvWRKY1 is identified to be a downstream target of HvMPK4 and phosphorylated by HvMPK4 in vitro in the presence of HvMKK1^(DD).Phosphorylation assay coupled with mutagenesis analyses identifies S122,T284,and S347 in HvWRKY1 as the major residues phosphorylated by HvMPK4.HvWRKY1 is phosphorylated in barley at the early stages of Bgh infection,which enhances its suppression on barley immunity likely due to enhanced DNA-binding and transcriptional repression activity.Our data suggest that the HvMKK1-HvMPK4 kinase pair acts upstream of HvWRKY1 to negatively regulate barley immunity against powdery mildew.

关键词： Barley MPK4 WRKY1 Phosphorylation Disease resistance Powdery mildew