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The chromosome-scale assembly of the Notopterygium incisum genome provides insight into the structural diversity of coumarins

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3760-3773页

作者： Qien Li Yiqun Dai Xin-Cheng Huang Lanlan Sun Kaixuan Wang Xiao Guo Dingqiao Xu Digao Wan Latai An Zixuan Wang Huanying Tang Qi Qi Huihui Zeng Minjian Qin Jia-Yu Xue Yucheng Zhao Tibetan medicine Research Center of Qinghai university Tibetan Medical CollegeQinghai UniversityXining 810016China School of pharmacy Bengbu Medical UniversityBengbu 233030China Department of Resources Science of Traditional Chinese medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China College of Horticulture Bioinformatics CenterAcademy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjing 210095China Key Laboratory of Shaanxi Administration of Traditional Chinese medicine for TCM Compatibility Shaanxi University of Chinese MedicineXi’an 712046China

Coumarins,derived from the phenylpropanoid pathway,represent one of the primary metabolites found in *** alignment of the tetrahydropyran(THP)and tetrahydrofuran(THF)rings with the lactone structure results in the formation of at least four types of complex ***,the mechanisms underlying the structural diversity of coumarin remain poorly ***,we report the chromosome-level genome assembly of Notopterygium incisum,spanning 1.64 Gb,with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding ***,we identified the key enzymes responsible for shaping the structural diversity of coumarins,including two p-coumaroyl CoA 2′-hydroxylases crucial for simple coumarins basic skeleton architecture,two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis,and five CYP736 cyclases involved in THP and THF ring ***,two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first *** analysis implies that tandem and ectopic duplications of the CYP736 subfamily,specifically arising in the Apiaceae,contributed to the structural diversity of coumarins in ***,this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

关键词： Notopterygium incisum Parallel evolution Biosynthesis Pyranocoumarins Furanocoumarins

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of Clinical pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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The role of botanical triterpenoids and steroids in bile acid metabolism,transport,and signaling:Pharmacological and toxicological implications

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3385-3415页

作者： Zichen Luo Wei Zhou Tong Xie Weichen Xu Chen Shi Zihan Xiao Yu Si Yan Ma Qingling Ren Liuqing Di Jinjun Shan Medical Metabolomics Center Institute of PediatricsJiangsu Key Laboratory of Children’s Health and Chinese MedicineNanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China Jiangsu CM Clinical medicine Innovation Center for Obstetrics Gynecologyand ReproductionAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210001China National Institute of Biological Sciences Beijing 102206China Jiangsu Engineering Research Center for Efficient Delivery System of TCM School of PharmacyNanjing University of Chinese MedicineNanjing 210023China

Bile acids(BAs)are synthesized by the host liver from cholesterol and are delivered to the intestine,where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various *** serve to emulsify dietary lipids and act as signaling molecules,regulating the host’s metabolism and immune homeostasis through specific ***,disruptions in BA metabolism,transport,and signaling are closely associated with cholestasis,metabolic disorders,autoimmune diseases,and *** triterpenoids and steroids share structural similarities with BAs,and they have been found to modulate BA metabolism,transport,and signaling,potentially exerting pharmacological ortoxicological ***,we have updated the research progress on BA,with a particular emphasis on new-found microbial ***,the latest advancements in targeting BA metabolism and signaling for disease treatment are ***,the roles of botanical triterpenoids in BA metabolism,transport,and signaling are examined,analyzing their potential pharmacological,toxicological,or drug interaction effects through these ***,a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

关键词： Bile acid Triterpenoid Phytosterol Saponin Gut microbes Cholestasis Metabolic disorders Rheumatoid arthritis

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LA-D-B1,a novel Abemaciclib derivative,exerts anti-breast cancer effects through CDK4/6

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BIOCELL 2024年第5期48卷 847-860页

作者： LING MA ZIRUI JIANG XIAO HOU YUTING XU ZIYUN CHEN SIYI ZHANG HANXUE LI SHAOJIE MA GENG ZHANG XIUJUN WANG JING JI Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening College of PharmacyJiangsu Ocean UniversityLianyungang222000China School of medicine Xiamen UniversityXiamen361102China

Background:Regulatory proteins involved in human cellular division and proliferation,cyclin-dependent kinases 4 and 6(CDK4/6)are overexpressed in numerous cancers,including triple-negative breast cancer(TNBC).TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis,and has a single treatment *** one of the CDK4/6 inhibitors,abemaciclib can effectively inhibit the growth of breast *** this study,we synthesized LA-D-B1,a derivative of Abemaciclib,and investigated its anti-tumor effects in breast ***:Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)*** cloning and migration abilities were determined by colony formation assay and wound healing *** invasion abilities and adhesion were determined by cell invasion assay and cell adhesion *** impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting,which quantified the levels of proteins associated with the cyclin-dependent kinase(CDK)4/6-cyclin D-Rb-E2F *** in vivo anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane(CAM)***:The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation,induced apoptosis,and caused cell cycle ***,LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway,including CDK4,CDK6 and *** results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor ***:In this study,LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast *** findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer.

关键词： CDK4/6 inhibitor Breast cancer Antitumor activity Cell cycle

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Sex-biased single-cell genetic landscape in mice with autism spectrum disorder

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Journal of Genetics and Genomics 2024年第3期51卷 338-351页

作者： Qian Zhang Yongjie Wang Jie Tao Ruixue Xia Yijie Zhang Zhirui Liu Jiwei Cheng Department of Neurology and Central Laboratory Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai 200062China School of pharmacy Hangzhou Normal UniversityHangzhouZhejiang 311121China Department of Respiratory and Critical Care medicine Henan University Huaihe HospitalKaifengHenan 475099China

Autistic spectrum disorder(ASD)is a male-biased,heterogeneous neurodevelopmental disorder that affects approximately 1%e2%of the *** exposure to valproic acid(VPA)is a recognized risk factor for ASD,but the cellular and molecular basis of VPA-induced ASD at the single-cell resolution is ***,we aim to compare the cellular and molecular differences in the hippocampus between male and female prenatal mice with ASD at the single-cell transcriptomic *** transcriptomes of more than 45,000 cells are assigned to 12 major cell types,including neurons,glial cells,vascular cells,and immune *** type-specific genes with altered expression after prenatal VPA exposure are analyzed,and the largest number of differentially expressed genes(DEGs)are found in neurons,choroid plexus epithelial cells,and *** microglia,several pathways related to inflammation are found in both males and females,including the tumor necrosis factor(TNF),nuclear factor kappa B(NF-kB),toll-like receptor(TLR),and mitogen-activated protein kinase(MAPK)signaling pathways,which are important for the induction of autistic-like ***,we note that several X-linked genes,including Bex1,Bex3,and Gria3,were among the male-specific DEGs of *** pioneering study describes the landscape of the transcriptome in the hippocampus of autistic *** elucidation of sexual differences could provide innovative strategies for the prevention and treatment of ASD.

关键词： Autistic spectrum disorder(ASD) Sex Single cell Neurons Microglia

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Pyronaridine combined with diminazene aceturate inhibits Babesia in vitro and in vivo

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 93-99页

作者： Shimaa Abd El-Salam El-Sayed Mohamed Z.Sayed-Ahmed Shaimaa Ahmed Awad Ali Nourah Alsadaan Nawazish Alam Mahmoud S.Alkhoudary Ikuo Igarashi Mohamed Abdo Rizk National Research Center for Protozoan Diseases Obihiro University of Agriculture and Veterinary MedicineInada-ChoObihiroHokkaido 080-8555Japan Department of Biochemistry and Chemistry of Nutrition Faculty of Veterinary MedicineMansoura UniversityMansoura 35516Egypt Department of Clinical pharmacy College of PharmacyJazan UniversityJazan 45142Saudi Arabia Medical-Surgical Department College of NursingJouf UniversitySakaka 72388Saudi Arabia Critical Care and Emergency Nursing Faculty of NursingMansoura UniversityEgypt College of Nursing Jouf UniversitySakaka 72388Saudi Arabia Faculty of pharmacy Mansoura UniversityMansoura 35516DakahliaEgypt Department of Internal medicine and Infectious Diseases Faculty of Veterinary MedicineMansoura UniversityMansoura 35516Egypt

Objective:To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in ***:Bioinformatic analysis was performed using atom pair *** in vitro combination test was performed against Babesia bovis and Theileria ***,the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory ***:Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular *** in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria *** addition,5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post *** combination therapy also normalized the hematological parameters of infected ***:An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice,suggesting it might be a new paradigm for the treatment of babesiosis.

关键词： Babesia Pyronaridine tetraphosphate Diminazene aceturate Babesiosis Theileria

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YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling

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Journal of Pharmaceutical Analysis 2024年第4期14卷 525-541页

作者： Hua Sui Wanli Deng Qiong Chai Bing Han Yuli Zhang Zhenzhen Wei Zan Li Ting Wang Jiling Feng Man Yuan Qingfeng Tang Hongxi Xu Medical Experiment Center Jiading Branch of Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai201803China Translational medicine Research Center for Cancer Prevention and Treatment Shanghai General Hospital Jiading Branch-School of Pharmacy of Shanghai University of Traditional Chinese Medicine Joint LaboratoryShanghai201803China Department of Medical Oncology Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China School of pharmacy Shanghai University of Traditional Chinese MedicineShanghai201203China The Second Clinical Medical College of Henan university of Traditional Chinese medicine Zhengzhou450000China Shanghai university of Traditional Chinese medicine Shanghai201203China Precision Research Center for Refractory Diseases Institute for Clinical ResearchShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai201620China

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon *** previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling ***,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is *** this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling ***,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a ***,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)***,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)***,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 ***,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in ***,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within

关键词： Tumor microenvironment Intestinal epithelial cells Treg/Th17 cells Metabolism Wnt5a/JNK signaling Tumorigenesis

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Clinical characteristics of delayed generalized erythema associated with cytarabine

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Chronic Diseases and Translational medicine 2024年第1期10卷 78-80页

作者： He Jiang Jun Lu Mei Wang College of pharmacy Anhui University of Chinese MedicineHefeiAnhuiChina Department of pharmacy Children's Hospital of Soochow UniversitySuzhouJiangsuChina

To the Editor,Cytarabine is one of the most used drugs for the treatment of hematological malignancies such as leukemia and non-Hodgkin's *** cells,cytarabine is activated into ara-CTP,which can replace deoxycytidine triphosphate(dCTP)and become incorporated into the DNA of proliferating ***,it can block DNA synthesis,resulting in proliferation arrest and cell death.

关键词： death drugs Clinical

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Active molecule-based theranostic agents for tumor vasculature normalization and antitumor efficacy

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Chinese Chemical Letters 2024年第8期35卷 229-234页

作者： Jin Wang Xiaoyan Pan Junyu Zhang Qingqing Zhang Yanchen Li Weiwei Guo Jie Zhang School of pharmacy Health Science CenterXi’an Jiaotong UniversityXi’an 710061China Center of Advanced Pharmaceuticals and Biomaterials State Key Laboratory of Natural MedicineChina Pharmaceutical UniversityNanjing 210009China

Tumor vascular normalization has emerged as a promising strategy for synergistic therapy *** on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic ***,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic ***,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.

关键词： Tumor vasculature normalization Diagnosis and treatment Cytotoxicity Depleting glutathione Ferroptosis Immune activation

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Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 758-771页

作者： Xin Han Yan Ning Xinyue Dou Yiwen Wang Qiyuan Shan Kao Shi Zeping Wang Chuan Ding Min Hao Kuilong Wang Mengyun Peng Haodan Kuang Qiao Yang Xianan Sang Gang Cao School of pharmacy Zhejiang Chinese Medical UniversityHangzhou311400China

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying *** vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-b(TGF-b).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw *** ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)*** note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and *** interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through *** conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

关键词： Liver fibrosis SIRT3 Cornus officinalis AMPK Caspase6

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