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Journal of Materials Science & Technology 2024年第5期172卷 145-155页

作者： Jingjing Zhang Yue Zhao Kezhen Qi Shu-yuan Liu College of Pharmacy Dali UniversityDali 671000China department of pharmacology Shenyang Medical CollegeShenyang 110034China

CuInS_(2)quantum-dot(CIS QD)-modified g-C_(3)N_(4)(CN)catalysts(CIS/CN)were prepared with the aid of an in-situ growth *** as-obtained photocatalysts were explored by measuring their crystallinity,surface morphology,binding energy and light absorption *** photocatalytic efficiency of the pho-tocatalysts was evaluated through photocatalytic water splitting for hydrogen production and tetracycline(TC)antibiotic degradation under the simulated solar light and visible light *** optimized sample(10CIS/CN)showed the best photocatalytic activity:producing 102.4μmol g^(-1)h^(-1)of hydrogen in 1 h,or degrading 52.16%of TC in 120 min,which were respectively 48 or 3.4 times higher than the photocatalytic activity of CN *** enhancement in the efficiency of the composite system was prin-cipally accredited to the enlargement of light absorption,the more effective in charge transfer and the dropping of the charge carrier pair recombination through a formed S-scheme heterojunctional *** work is an effort to adjust CN-based polysulfide QD for speedy *** enriched photo-catalytic activity grants a new sense for adjusting the optical properties of CN.

关键词： CuInS_(2)QDs g-C_(3)N_(4) Photocatalysis Hydrogen production S-scheme heterojunction

The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extend Caenorhabditis elegans lifespan and healthspan

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3266-3280页

作者： Wenfeng Li Shuming Chen Jing Lang Jing Luo Jiahui Chen Liping Zhang Zhijie Sun Deli Dong department of pharmacology China Pharmaceutical UniversityNanjing 210009China

The drugs extending healthspan in clinic have always been *** is an FDA-approved clinical antiprotozoal *** is rapidly metabolized to tizoxanide after absorption in *** previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and ***,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 ***,both nitazoxanide and tizoxanide improve high glucose-induced shortening of *** *** has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.

关键词： Nitazoxanide Tizoxanide C.elegans Healthspan Lifespan AMPK Akt Mitochondrial uncoupling

Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) via dephosphorylation of the EGFR signaling pathway

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Journal of Biomedical Research 2024年第4期38卷 382-396页

作者： Muhammad Zubair Hafiz Jie Pan Zhiwei Gao Ying Huo Haobin Wang Wei Liu Jian Yang department of pharmacology Nanjing Medical UniversityNanjingJiangsu 211166China

The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer *** in vivo experiments were conducted on nude and ICR *** a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver *** the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ *** in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)*** with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 ***,other CAR target genes also showed a significant increase in the *** up-regulation of murine CAR was observed in the liver tissues of both nude and ICR *** findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator *** of the ERK1/2 signaling pathway was also observed in ***,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and *** the nude mice,T-AⅢ also inhibited EGFR *** results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.

关键词： timosaponin AⅢ CAR metabolism enzyme ERK1/2 signaling pathway EGFR signaling pathway

Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome

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Oncology Research 2024年第5期32卷 911-923页

作者： JINGJING CHEN DAN WANG ZEQUN WANG MENGYUAN HAN HOUQING YIN WENTING ZHOU RIBAI YAN YAN PAN department of pharmacology School of PharmacyChangzhi Medical CollegeChangzhiChina2 Department of PharmacologySchool of Basic Medical SciencesHealth Science CenterPeking UniversityBeijingChina3 Beijing Key Laboratory of Tumor Systems BiologyPeking UniversityBeijingChina4 Department of PharmacologyXinjiang Medical UniversityUrumqiChina5 School of Pharmaceutical SciencesPeking UniversityBeijingChina

Photodynamic therapy(PDT)is a promising cancer *** study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,*** apoptosis-and autophagy-related proteins were examined using western *** sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after *** results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 *** ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced ***-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or *** level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after *** Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA *** Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle ***-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting ***,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling *** associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

关键词： Photodynamic therapy ROS Apoptosis Autophagy Bioinformatic analysis

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2429-2438页

作者： Peng-Fei Jing Jin Chen En-Da Yu Chao-Yu Miao department of Colorectal Surgery Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China department of Endocrinology and Metabolism Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China department of pharmacology Second Military Medical University/Naval Medical UniversityShanghai 200433China

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has been *** the popularization of endoscopic technology,a number of early CRC has been ***,despite current treatment methods,some patients with early CRC still experience postoperative recurrence and *** To search for indicators associated with early CRC recurrence and metastasis to identify high-risk *** A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this *** of blood routine test,liver and kidney function tests and tumor markers were collected before *** were followed up through disease-specific database and telephone *** recurrence,metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and *** We comprehensively compared the predictive value of preoperative blood routine,blood biochemistry and tumor markers for disease-free survival(DFS)and overall survival(OS)of *** multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS[hazard ratio(HR)=0.995,95% confidence interval(CI):0.991-0.999,P=0.015],while serum carcinoembryonic antigen(CEA)level(HR=1.008,95%CI:1.001-1.016,P=0.027)and serum total cholesterol level(HR=1.538,95%CI:1.026-2.305,P=0.037)were independent risk factors for *** cutoff value of serum CEA level for predicting OS was 2.74 ng/*** the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level,the difference between the two groups was not statistically significant(P=0.075).CONCLUSION For patients with T2N0M0 or T3N0M0 CRC,preoperative platelet count was a protective factor for DFS,while serum CEA level was an independent risk factor for *** that these measures are easier to detect and more acceptable to patients,they may have broader applications.

关键词： Colorectal cancer Platelet count Serum carcinoembryonic antigen Total cholesterol level Overall survival Disease-free survival

Prenatal prednisone exposure disturbs fetal kidney development and its characteristics

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Journal of Environmental Sciences 2024年第11期145卷 75-87页

作者： Zhiping Xia Songdi Wang Wen Wang Yutang Liu Tianshu Yang Hui Wang Ying Ao department of pharmacology Wuhan University School of Basic Medical SciencesWuhan 430071China Hubei Provincial Key Laboratory of Developmentally Originated Disease Wuhan 430071China

Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary ***,it is also recognized as an emerging environmental *** be exposed to prednisone actively or passively throughmultiple pathways and cause developmental toxicity to the ***,the impact of prenatal prednisone exposure(PPE)on fetal kidney development remains *** this study,pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses(0.25,0.5,or 1 mg/(kg·day)),or at the dose of 1 mg/(kg·day)in different gestational days(GD)(GD0-9,GD10-18,or GD0-18).The pregnant mice were euthanized on *** staining revealed fetal kidney dysplasia,with an enlarged glomerular Bowman’s capsule space and a reduced capillary network in the PPE *** expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE ***,overall gene expression in renal tubules and collecting ducts were markedly *** of the above effects were more pronounced in high-dose,full-term pregnancy,and female *** on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2,increased the expression of Hnf1β,Hnf4α,and Wnt9b,and inhibited the expression of glial cell line-derived neurotrophic factor(GDNF)and Notch signaling *** conclusion,this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney,and the time effect is manifested as full-term pregnancy>early pregnancy>mid-late pregnancy.

关键词： Prenatal prednisone exposure Kidney developmental toxicity Glomerulus Toxicity characteristics

Prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

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Journal of Environmental Sciences 2024年第3期137卷 287-301页

作者： Yongguo Dai Yu Peng Wen Hu Yi Liu Hui Wang department of pharmacology Wuhan University School of Basic Medical SciencesWuhan 430071China department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Provincial Key Laboratory of Developmentally Originated Disease Wuhan 430071China

Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse ***,systematic studies about the developmental toxicity of amoxicillin are still *** explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the ***,PAmE altered multiple maternal/fetal serum phenotypes,especially in *** multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>*** analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response *** conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.

关键词： Amoxicillin Prenatal exposure Fetal development Organ function Developmental toxicity

Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1711-1725页

作者： Yingting Wu Jiaqi Xin Xinyu Li Ting Yang Yi Liu Yongsheng Zhao Wen Xie Mengxi Jiang department of pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China department of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Center for Pharmacogenetics and department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100069China

Drug repurposing offers an efficient approach to therapeutic *** this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal *** went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in *** with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy ***,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent *** results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor *** summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.

关键词： Lansoprazole Proton pump inhibitors Adipose thermogenesis Energy expenditure Metabolic syndrome PHOSPHO1 inhibitor Cannabinoid receptor signaling Drug repurposing

CRABP1-mediated non-canonical retinoic acid signaling in motor neurons and neural stem cells

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Neural Regeneration Research 2024年第6期19卷 1169-1170页

作者： Li-Na Wei department of pharmacology University of Minnesota Medical SchoolMinneapolisMNUSA

Retinoic acid(RA),the active metabolite of vitamin A(the retinoids),elicits a wide spectrum of biological activities critical to the development and health of most of the organ systems including the nervous systems(Corcoran et al.,2002).The effects of RA are mediated by two very distinct pathways;the first is manifested in the nucleus by binding to a large family of nuclear RA receptors(RARs)to regulate proper expression of RAtargeted genes.

关键词： canonical spectrum critical

Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

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Journal of Pharmaceutical Analysis 2024年第4期14卷 439-459页

作者： Lan Chen Yuan Zhang Yi-Xin Zhang Wei-Lai Wang De-Mei Sun Peng-Yun Li Xue-Song Feng Yue Tan School of Pharmacy China Medical UniversityShenyang110122China Institute of pharmacology.and Toxicology Institution National Engineering Research Center for Strategic DrugsBeijing100850China department of Gastroenterology Shengjing Hospital of China Medical UniversityShenyang110022China

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling ***,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse ***,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different *** paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since *** also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing *** addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

关键词： TKIs Microextraction technique HRMS methods Pharmacokinetic studies Therapeutic drug monitoring