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Oroxyloside protects against dextran sulfate sodium-induced colitis by inhibiting ER stress via PPARγ activation

Chinese Journal of Natural medicines 2024年第4期22卷 307-317页

作者： TAO Lei DOU Renjie CHEN Xueming CAO Yu DAI Zhen HU Ziyan MA Zhi GE Xiaoming ZHANG Ling WANG Xiaoping Nanjing Institute for Food and Drug control Nanjing 211198China State Key Laboratory of Natural medicines School of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 211198China

Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), may result from immune system dysfunction, leading to the sustained overproduction of reactive oxygen species (ROS) and subsequent cellular oxidative stress damage. Recent studies have identified both peroxisome proliferator-activated receptor-γ (PPARγ) and endoplasmic reticulum (ER) stress as critical targets for the treatment of IBD. Oroxyloside (C22H20O11), derived from the root of Scutellaria baicalensis Georgi, has traditionally been used in treating inflammatory diseases. In this study, we investigated the molecular mechanisms by which oroxyloside mitigates dextran sulfate sodium (DSS)-induced colitis. We examined the effects of oroxyloside on ROS-mediated ER stress in colitis, including the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, and CHOP, which are associated with ER stress. The beneficial impact of oroxyloside was reversed by the PPARγ antagonist GW9662 (1 mg·kg^(−1), i.v.) in vivo. Furthermore, oroxyloside decreased pro-inflammatory cytokines and ROS production in both bone marrow-derived macrophages (BMDM) and the mouse macrophage cell line RAW 264.7. However, PPARγ siRNA transfection blocked the anti-inflammatory effect of oroxyloside and even abolished ROS generation and ER stress activation inhibited by oroxyloside in vitro. In conclusion, our study demonstrates that oroxyloside ameliorates DSS-induced colitis by inhibiting ER stress via PPARγ activation, suggesting that oroxyloside might be a promising effective agent for IBD.

关键词： Oroxyloside ER stress PPARγ Colitis

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Chemical derivatization strategies for enhancing the HPLC analytical performance of natural active triterpenoids

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Journal of pharmaceutical Analysis 2024年第3期14卷 295-307页

作者： Xiao-Feng Huang Ying Xue Li Yong Tian-Tian Wang Pei Luo Lin-Sen Qing Chengdu Institute of Biology Chinese Academy of SciencesChengdu610041China State Key Laboratory for quality Research in Chinese medicines Macao University of Science and TechnologyMacaoChina Sichuan Center for Disease control and Prevention Chengdu610041China University of Chinese Academy of Sciences Beijing100049China

Triterpenoids widely exist in nature,displaying a variety of pharmacological *** triterpenoids in different matrices,especially in biological samples holds great ***-performance liquid chromatography(HPLC)has become the predominant method for triterpenoids analysis due to its exceptional analytical ***,due to the structural similarities among botanical samples,achieving effective separation of each triterpenoid proves challenging,necessitating significant improvements in analytical ***,triterpenoids are characterized by a lack of ultraviolet(UV)absorption groups and chromophores,along with low ionization efficiency in mass ***,routine HPLC analysis suffers from poor *** derivatization emerges as an indispensable technique in HPLC analysis to enhance its *** the structural characteristics of triterpenoids,various derivatization reagents such as acid chlorides,rhodamines,isocyanates,sulfonic esters,and amines have been employed for the derivatization analysis of *** review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of ***,the limitations and challenges encountered in previous studies are discussed,and future research directions are proposed to develop more effective derivatization methods.

关键词： Triterpenoid HPLC Derivatization Quantification

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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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Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 795-807页

作者： Yongchun Pan Xiaowei Luan Fei Zeng Xuyuan Wang Shurong Qin Qianglan Lu Guanzhong He Yanfeng Gao Xiaolian Sun Xin Han Bangshun He Yujun Song Department of Laboratory Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 210006China College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China State Key Laboratory of Natural medicines Key Laboratory of Drug Quality Control and PharmacovigilanceDepartment of Pharmaceutical AnalysisChina Pharmaceutical UniversityNanjing 211198China School of Medicine&Holistic Integrative Medicine Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene ***,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor ***,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer *** this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are *** intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as *** the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target *** tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation ***,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

关键词： CRISPRdelivery Enzymeencapsulation Logic gate Hybridmaterial Hypoxia Gene editing Precise nanomedicine Multimodal therapy

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STING signaling in islet macrophages impairs insulin secretion in obesity

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Science China(Life Sciences) 2024年第2期67卷 345-359页

作者： Ze Hong Saihua Chen Jing Sun Dan Cheng Hanli Guo Jiahao Mei Xiang Zhang Munire Maimaiti Haiping Hao Peng Cao Haiyang Hu Chen Wang School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural medicines Department of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198China School of Life Sciences Westlake UniversityHangzhou 310012China

The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune *** immune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully ***,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)***^(-/-)alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of ***,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in ***,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment ofβcell insulin secretory *** inhibiting STING activation enhances insulin secretion to control ***,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in dietinduced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.

关键词： STING obesity type 2 diabetes insulin macrophages islet

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In situ and on-line monitoring of cadmium in soil pore water using an automatic sampling integrated electrochemical sensor

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Science China Technological Sciences 2024年第9期67卷 2894-2904页

作者： KUANG JiaJie WEN JunLin CAI XiXi ZHOU LiHua YUAN Yong Guangdong Key Laboratory of Environmental Catalysis and Health Risk control School of Environmental Science and EngineeringInstitute of Environmental Health and Pollution ControlGuangdong University of Technology School of Biomedical and pharmaceutical Sciences Guangdong University of Technology

Cadmium（Cd） contamination in soil pore water is the primary pathway for Cd uptake by food crops,such as rice（Oryza sativa L.）,posing significant risks to both food safety and human *** study presents a novel soil pore water metal sensor（SPW-Msensor） for in situ and online monitoring of Cd in soil pore water(Cdpw).The SPW-Msensor integrates an automated sampling device,comprising a Rhizon sampler and a reciprocating series pump with an independent dual plunger drive,along with a portable electrochemical sensor consisting of a screen-printed electrode,flow cell,and portable *** SPW-Msensor enables the detection of Cd within a linear range of 50 to 300 ppb while exhibiting high anti-interference ***,it demonstrates excellent repeatability(relative standard deviation values（RSDs）quality score（Q2） of 0.69,adjusted R2of 0.9345,and root mean square error（RMSE） of *** SPW-Msensor demonstrates real-time monitoring capabilities for assessing Cd levels in acidified *** SPW-Msensor offers an efficient approach for in-situ and continuous monitoring of Cdpwthat provides valuable insights applicable to environmental and agricultural domains.

关键词： cadmium pore water electrochemical sensor in-situ monitoring soil

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A novel alternative for pyrogen detection based on a transgenic cell line

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1221-1229页

作者： Qing He Chuan-Fei Yu Gang Wu Kai-Qin Wang Yong-Bo Ni Xiao Guo Zhi-Hao Fu Lan Wang De-Jiang Tan Hua Gao Can Wang Gang Chen Xu-Hong Chen Bo Chen Jun-Zhi Wang National Institutes for Food and Drug control BeijingChina School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyangChina Shanghai Institute for Food and Drug control ShanghaiChina KeyMed Biosciences Inc. ChengduChina

Pyrogen,often as a contaminant,is a key indicator affecting the safety of almost all parenteral drugs(including biologicals,chemicals,traditional Chinese medicines and medical devices).It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted‘reduction,replacement and refinement’principle,which has been highly considered by regulatory agencies from different *** used NF-κB,a central signalling molecule mediating inflammatory responses,as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence ***,we show that this test can quantitatively and sensitively detect endotoxin(lipopolysaccharide from different strains)and nonendotoxin(lipoteichoic acid,zymosan,peptidoglycan,lectin and glucan),has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals(group A&C meningococcal polysaccharide vaccine;basiliximab;rabies vaccine(Vero cells)for human use,freeze-dried;Japanese encephalitis vaccine(Vero cells),inactivated;insulin aspart injection;human albumin;recombinant human erythropoietin injection(CHO Cell)).The within-laboratory reproducibility of the test in three independent laboratories was 85%,80%and 80%and the interlaboratory reproducibility among laboratories was 83.3%,95.6%and 86.7%.The sensitivity(true positive rate)and specificity(true negative rate)of the test were 89.9%and 90.9%,*** summary,the test provides a novel alternative for pyrogen detection.

关键词： pyrogen rabbit replace

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Analysis of GC×GC fingerprints from medicinal materials using a novel contour detection algorithm:A case of Curcuma wenyujin

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Journal of pharmaceutical Analysis 2024年第4期14卷 542-551页

作者： Xinyue Yang Yingyu Sima Xuhuai Luo Yaping Li Min He Department of pharmaceutical Engineering School of Chemical EngineeringXiangtan UniversityXiangtanHunan411105China Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha410082China Department of quality control Xiangtan Central HospitalXiangtanHunan411100China

This study introduces an innovative contour detection algorithm,PeakCET,designed for rapid and efficient analysis of natural product image fingerprints using comprehensive two-dimensional gas chromatogram(GC×GC).This method innovatively combines contour edge tracking with affinity propagation(AP)clustering for peak detection in GC×GC fingerprints,the first in this *** edge tracking signif-icantly reduces false positives caused by“burr”signals,while AP clustering enhances detection accuracy in the face of false *** efficacy of this approach is demonstrated using three medicinal products derived from Curcuma *** not only performs contour detection but also employs inter-group peak matching and peak-volume percentage calculations to assess the compositional similarities and differences among various ***,this algorithm compares the GC×GC fingerprints of Radix/Rhizoma Curcumae Wenyujin with those of products from different botanical *** findings reveal that genetic and geographical factors influence the accumulation of secondary metabolites in various plant *** sample exhibits unique characteristic components alongside common ones,and vari-ations in content may influence their therapeutic *** research establishes a foundational data-set for the quality assessment of Curcuma products and paves the way for the application of computer vision techniques in two-dimensional(2D)fingerprint analysis of GC×GC data.

关键词： GC×GC Image fingerprints Contour detection Clustering of mass spectra Curcuma products

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Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 667-681页

作者： Yue Zhang Jingwen Gao Na Li Peng Xu Shimeng Qu Jinqian Cheng Mingrui Wang Xueru Li Yaheng Song Fan Xiao Xinyu Yang Jihong Liu Hao Hong Ronghao Mu Xiaotian Li Youmei Wang Hui Xu Yuan Xie Tianming Gao Guangji Wang Jiye Aa Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural MedicinesResearch Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical SciencesChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Monitoring and control Drug Intelligence and Forensic CenterMinistry of Public SecurityBeijing 100193China School of Pharmacy China Pharmaceutical UniversityNanjing 211198China School of Foreign Languages China Pharmaceutical UniversityNanjing 211198China Department of Neurobiology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Pharmacology China Pharmaceutical UniversityNanjing 211198China School of pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China

Studies have suggested that the nucleus accumbens(NAc)is implicated in the pathophysiology of major depression;however,the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been ***,we identified a specific reduction of cyclic adenosine monophosphate(cAMP)in the subset of dopamine D1 receptor medium spiny neurons(D1-MSNs)in the NAc that promoted stress susceptibility,while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like *** treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons(D2-MSNs)of depressed mice,however,the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc *** discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration,but not a lower *** fast onset property of crocin was verified through multicenter ***,crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on *** findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc,and provide a potential rapid antidepressant drug candidate,crocin.

关键词： CAMP Nucleus accumbens Depression D1-MSN D2-MSN

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Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics

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Journal of pharmaceutical Analysis 2024年第6期14卷 785-804页

作者： Patanachai K.Limpikirati Sorrayut Mongkoltipparat Thinnaphat Denchaipradit Nathathai Siwasophonpong Wudthipong Pornnopparat Parawan Ramanandana Phumrapee Pianpaktr Songsak Tongchusak Maoxin Tim Tian Trairak Pisitkun Department of Food and pharmaceutical Chemistry Faculty of Pharmaceutical SciencesChulalongkorn UniversityPathumwanBangkok10330Thailand pharmaceutical Sciences and technology(PST)Graduate Program Faculty of Pharmaceutical SciencesChulalongkorn UniversityPathumwanBangkok10330Thailand Center of Excellence in Systems Biology(CUSB) Faculty of MedicineChulalongkorn UniversityPathumwanBangkok10330Thailand Department of pharmaceutical Chemistry Faculty of Pharmaceutical SciencesHuachiew Chalermprakiet UniversityBang PhliSamut Prakan10540Thailand Division of Research Affairs Faculty of MedicineChulalongkorn UniversityPathumwanBangkok10330Thailand

In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and *** specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered *** of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance *** attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the *** criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric *** in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial *** are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

关键词： Biopharmaceutical analysis Biopharmaceutical quality control Biopharmaceutical specifications Monoclonal antibodies Protein therapeutics Regulatory science

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