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药物分析学报（英文）
西安交通大学
药物分析学报（英文）

西安交通大学

双月刊

2095-1779

jpa2011@126.com

029-82655433

710061

西安市雁塔西路76号

药物分析学报（英文）/Journal Journal of Pharmaceutical AnalysisCSCD北大核心SCI
查看更多>>《药物分析学报（英文）》（Journal of Pharmaceutical Analysis，简称JPA），2011年创刊，双月刊，为大16开本，系教育部主管、西安交通大学主办的药物分析专业英文期刊。JPA以搭建高水平的国际学术交流平台、创办具有国际影响力的高水平的专业学术期刊为办刊宗旨。主要报道药物分析新方法、新技术，药品质量控制和用药安全等最新研究成果。创刊之初与Elsevier国际出版集团合作，已组建国际化编委会，采用EVISE投稿审稿系统，开放获取，通过ScienceDirect平台在线向全球读者开放阅读，实现稿源国际化、同行评议国际化、出版国际化和读者国际化。
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    Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis

    Yini BaoQiyuan ShanKeda LuQiao Yang...
    1099-1109页
    查看更多>>摘要：Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibro-blast activation,and immune cell recruitment.In this review,we summarize recent advances in un-derstanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Multiple roles of arsenic compounds in phase separation and membraneless organelles formation determine their therapeutic efficacy in tumors

    Meiyu QuQiangqiang HeHangyang BaoXing Ji...
    1110-1124页
    查看更多>>摘要：Arsenic compounds are widely used for the therapeutic intervention of multiple diseases.Ancient pharmacologists discovered the medicinal utility of these highly toxic substances,and modern phar-macologists have further recognized the specific active ingredients in human diseases.In particular,Arsenic trioxide(ATO),as a main component,has therapeutic effects on various tumors(including leukemia,hepatocellular carcinoma,lung cancer,etc.).However,its toxicity limits its efficacy,and con-trolling the toxicity has been an important issue.Interestingly,recent evidence has pointed out the pivotal roles of arsenic compounds in phase separation and membraneless organelles formation,which may determine their toxicity and therapeutic efficacy.Here,we summarize the arsenic compounds-regulating phase separation and membraneless organelles formation.We further hypothesize their potential involvement in the therapy and toxicity of arsenic compounds,highlighting potential mecha-nisms underlying the clinical application of arsenic compounds.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Natural compounds improve diabetic nephropathy by regulating the TLR4 signaling pathway

    Jiabin WuKe LiMuge ZhouHaoyang Gao...
    1125-1139页
    查看更多>>摘要：Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Toll-like receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or vi-ruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis

    Weilun ChengWanqi MiShiyuan WangXinran Wang...
    1140-1157页
    查看更多>>摘要：Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4

    Zewen ChuMiao ZhuYuanyuan LuoYaqi Hu...
    1158-1175页
    查看更多>>摘要：Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Melatonin enhances the efficacy of anti-PD-L1 by improving hypoxia in residual tumors after insufficient radiofrequency ablation

    Yanqiao RenLicheng ZhuYusheng GuoJinqiang Ma...
    1176-1188页
    查看更多>>摘要：The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Baicalein:A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement

    Na LiuXin CuiWenhui YanTingli Guo...
    1189-1204页
    查看更多>>摘要：There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Increasing the tumour targeting of antitumour drugs through anlotinib-mediated modulation of the extracellular matrix and the RhoA/ROCK signalling pathway

    Xuedan HanJialei LiuYidong ZhangEric Tse...
    1205-1221页
    查看更多>>摘要：Anlotinib has strong antiangiogenic effects and leads to vessel normalization.However,the"window period"characteristic in regulating vessel normalization by anlotinib cannot fully explain the long-term survival benefits achieved through combining it with other drugs.In this study,through RNA sequencing(RNA-seq)and label-free quantitative proteomics analysis,we discovered that anlotinib regulated the expression of components of the extracellular matrix(ECM),leading to a significant reduction in ECM stiffness.Our bioinformatic analysis revealed a potential positive relationship between the ECM pathway and gefitinib resistance,poor treatment outcomes for programmed death 1(PD-1)targeting,and unfavourable prognosis following chemotherapy in lung cancer patients.We administered anlotinib in combination with these antitumour drugs and visualized their distribution using fluorescent labelling in various tumour types.Notably,our results demonstrated that anlotinib prolonged the retention time and distribution of antitumour drugs at the tumour site.Moreover,the combination therapy induced notable loosening of the tumour tissue structure.This reduction was associated with decreased interstitial fluid pressure and tumour solid pressure.Additionally,we observed that anlotinib effectively suppressed the Ras homologue family member A(RhoA)/Rho-associated protein kinase(ROCK)signalling pathway.These findings suggest that,in addition to its antiangiogenic and vessel normalization effects,anlotinib can increase the distribution and retention of antitumour drugs in tumours by modulating ECM expression and physical properties through the RhoA/ROCK signalling pathway.These valuable insights contribute to the development of combination therapies aimed at improving tumour targeting in cancer treatment.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Hepatic protein phosphatase 1 regulatory subunit 3G alleviates obesity and liver steatosis by regulating the gut microbiota and bile acid metabolism

    Chu ZhangGui WangXin YinLingshan Gou...
    1222-1237页
    查看更多>>摘要：Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据

    Mapping conformational changes on bispecific antigen-binding biotherapeutic by covalent labeling and mass spectrometry

    Arnik ShahDipanwita BatabyalDayong QiuWeidong Cui...
    1238-1246页
    查看更多>>摘要：Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling and fast photooxidation of proteins(FPOP),in conjunction with mass spectrometry(MS),to investigate structural modifications for the new class of immuno-oncological therapy known as bis-pecific antigen-binding biotherapeutics(BABB).The evaluated techniques unveiled subtle structural changes occurring at the amino acid residue level within the antigen-binding domain under both native and thermal stress conditions,which cannot be detected by conventional biophysical techniques,e.g.,near-ultraviolet circular dichroism(NUV-CD).The determined variations in labeling uptake under native and stress conditions,corroborated by binding assays,shed light on the binding effect,and highlighted the potential of covalent-labeling methods to effectively monitor conformational changes that ultimately influence the product quality.Our study provides a foundation for implementing the developed tech-niques in elucidating the inherent structural characteristics of novel therapeutics and their conforma-tional stability.
      原文链接:
    • 国家科技期刊平台
    • NETL
    • NSTL
    • 万方数据