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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

A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent Prunus species of southeast Asia

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Journal of Traditional Chinese Medicine 2024年第3期44卷 620-628页

作者： Shikha Agrawal Adarsh Kumar Ankit Kumar Singh Harshwardhan Singh Suresh Thareja Pradeep Kumar department of pharmaceutical Sciences and Natural Products Central University of Punjab

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian subcontinent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent,it extends from the Himalayas to Sikkim, Meghalaya,Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological,microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory,hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus species from its distribution, morphological characters to phytoconstituents, and pharmacological activity.

关键词： Prunus Rosaceae antineoplastic agents distribution hypoglycemic agents phytochemistry review

Pharmacological potential of Manilkara zapota(L.)***(Sapodilla):a narrative review

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Journal of Traditional Chinese Medicine 2024年第2期44卷 403-407页

作者： Priyanka Sharma Aakash Deep Harish Kumar Nitin Bansal Sanjiv Kumar Arun Davinder Kumar department of pharmaceutical Sciences Chaudhary Bansi Lal UniversityBhiwani 127021India department of pharmaceutical Sciences Maharishi Dayanand UniversityRohtak 124001India

Herbal medicine is safe and effective in treating various *** herbal medicine plays a tremendous role in treatment of various diseases and accompanying complications,hence herbal medicine requires remarkable attention in further research for the development of numerous active formulations for treatment of health *** plant needs special consideration for development and research of unidentified compound and characterization of novel active molecules that overcome multiple pathological *** genus Manilkara contains 135 plants around the *** overview discusses all the virtues of most important and commonly used plant Manilkara zapota(L.)***(***),also known as *** has various traditional beneficial effects in treatment of various diseases and disorders dating back to prehistoric times and used in ancient traditional system of herbal medicine.

关键词： herbal medicine Manilkara zapota phytoconstituents pharmacological activity review

Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiati

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World Journal of Stem Cells 2024年第2期16卷 102-113页

作者： Pakkath Narayanan Arya Iyyappan Saranya Nagarajan Selvamurugan department of Biotechnology School of BioengineeringSRM Institute of Science and TechnologyKattankulathur 603203India

Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and *** studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic *** is the process by which new bones are formed;it also aids in bone ***/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for ***/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the *** studies have indicated that these two signaling pathways contribute to osteogenic *** Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling ***,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical *** review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.

关键词： Bone Mesenchymal stem cells Osteogenic differentiation Wnt/β-catenin Bone morphogenetic proteins

Magnesium-incorporated biocomposite scaffolds:A novel frontier in bone tissue engineering

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Journal of Magnesium and Alloys 2024年第6期12卷 2231-2248页

作者： Abinaya Shanmugavadivu Sundaravadhanan Lekhavadhani Sushma Babu Nivetha Suresh Nagarajan Selvamurugan department of Biotechnology School of BioengineeringCollege of Engineering and TechnologySRM Institute of Science and TechnologyKattankulathur603203Tamil NaduIndia

Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting *** the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and ***,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite *** scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone *** review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel *** these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical *** limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of *** review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.

关键词： Magnesium Bone tissue engineering Immunomodulation Osteogenesis Angiogenesis

In vitro engineered models of neurodegenerative diseases

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BIOCELL 2024年第1期48卷 79-96页

作者： ZEHRA GÜL MORÇIMEN ŞEYMA TAŞDEMIR AYLIN ŞENDEMIR bioengineering department Graduate School of Natural and Applied SciencesEge UniversityIzmir35040Türkiye bioengineering department Faculty of Engineering and Natural ScienceCelal Bayar UniversityManisa45110Türkiye bioengineering department Ege UniversityIzmir35040Türkiye department of Biomedical Technologies Graduate School of Natural and Applied SciencesEge UniversityIzmir35040Türkiye

Neurodegeneration is a catastrophic process that develops progressive damage leading to functional andstructural loss of the cells of the nervous system and is among the biggest unavoidable problems of our *** do not reflect the pathophysiology observed in humans due to distinct differences between the neuralpathways,gene expression patterns,neuronal plasticity,and other disease-related mechanisms in animals *** in vitro cell culture models are also not sufficient for pre-clinical drug testing in reflecting thecomplex pathophysiology of neurodegenerative ***,modern,engineered techniques are applied to developmulticellular,intricate in vitro models and to create the closest microenvironment simulating biological,biochemical,and mechanical characteristics of the in vivo degenerating *** THIS review,the capabilities and shortcomings ofscaffold-based and scaffold-free techniques,organoids,and microfluidic models that best reflect neurodegeneration invitro in the biomimetic framework are discussed.

关键词： Neurodegenerative diseases In vitro models Scaffolds Organoids Microfluidic devices

Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization

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Nano Research 2024年第4期17卷 2908-2918页

作者： Guanting Li Fengli Xia Hongying Xiao Shunzhe Zheng Shuwen Fu Han Qiao Qianhui Jin Xuanbo Zhang Dun Zhou Chutong Tian Jin Sun Zhonggui He Bingjun Sun department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Emergency department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery ***,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous *** rational design of camptothecins-based prodrug nanoassemblies remains a ***,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug ***,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical *** length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and ***,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and *** findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based nanomedicines.

关键词： prodrug nanoassembly self-assembly antitumor efficacy tolerance 7-ethyl-10-hydroxycamptothecin(SN_(3)8)

Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice

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Neural Regeneration Research 2024年第2期19卷 416-424页

作者： Guixiang Wang Wenjia Wang Ye Zhang Xiaoying Gou Qingqing Zhang Yanmiao Huang Kuo Zhang Haotian Zhang Jingyu Yang Yuting Li Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyangLiaoning ProvinceChina department of Pharmacology Shenyang Pharmaceutical UniversityShenyangLiaoning ProvinceChina

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal *** this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate *** found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive *** markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to ***(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in *** mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 *** vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

关键词： adolescence adulthood ethanol dentate gyrus EZH2 in vivo tracing lineage progression mTOR neural stem cell newborn dendritic spine newborn neurons

Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

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Chinese Chemical Letters 2024年第2期35卷 323-328页

作者： Qiu Wang Qikun Jiang Dan Li Zimeng Yang Lin Gao Fan Liu Chang Li Yao Feng Zhonggui He Cong Luo Jin Sun department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Kangya of Ningxia pharmaceutical Co.Ltd. Yinchuan 750000China

Small interfering RNA(siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory ***,the effective delivery of siRNA to desired destination still remains challenging due to poor stability,high molecular weight and negative ***,ionizable lipid nanoparticle(LNP)has been extensively used as vector for effective delivery of ***,we report a mannose-modified LNP(M-MC_(3) LNP@TNFα)loading tumor necrosis factorα(TNFα)siRNA for targeting liver macrophages,achieving effectively inhibit acute liver *** M-MC_(3) LNP@TNFαnot only increases the internalization of LNP by macrophages,but also enhances the gene silencing efficiency of TNFαin ***,the M-MC_(3) LNP@TNFαexhibits higher accumulation in liver of healthy mice than that of MC_(3) LNP@TNFα(un-modified LNP)owing to the targeting effect of *** expected,the M-MC_(3) LNP@TNFαsignificantly suppresses the expression of TNFαand ameliorates liver damage in acute liver injury *** a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

关键词： Lipid nanoparticle Targeting siRNA delivery Acute liver injury Gene silencing Tumor necrosis factorα

Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

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Journal of Traditional Chinese Medicine 2024年第3期44卷 515-523页

作者： WANG Xiang HUANG Jianping WANG Yupeng WANG Qilong JING Yajiang ZHANG Gang PENG Liang GAO Jing WANG Hongyan YAN Yonggang department of Key Laboratory of "Qin pharmaceutical" Research and Development Shaanxi University of Traditional Chinese Medicine department of Yupeng Shaanxi Haitian pharmaceutical Co. Ltd. department of Acupuncture and Tuina Shaanxi University of Traditional Chinese Medicine

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

关键词： Dahuang () Taoren () differential metabolites kernel drug pairs metabolic networks and pathways metabolomics