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Crocus genome reveals the evolutionary origin of crocin biosynthesis

Acta Pharmaceutica Sinica B 2024年第4期14卷 1878-1891页

作者： Zhichao Xu Shanshan Chen Yalin Wang Ya Tian Xiaotong Wang Tianyi Xin Zishan Li Xin Hua Shengnan Tan Wei Sun Xiangdong Pu Hui Yao Ranran Gao Jingyuan Song Key Lab of chinese Medicine Resources Conservation State Administration of Traditional Chinese Medicine of the People's Republic of ChinaInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China State Key Laboratory of Basis and New Drug Development of Natural and Nuclear Drugs Engineering Research Center of Chinese Medicine ResourceMinistry of EducationBeijing 100193China College of Life Science Northeast Forestry UniversityHarbin 150040China Key Laboratory of Beijing for Identification and Safety Evaluation of chinese Medicine China Academy of Chinese Medical SciencesInstitute of Chinese Materia MedicaBeijing 100700China Analysis and Testing Center of Northeast Forestry University Harbin 150040China school of Pharmacy Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui ProvinceHefei 230032China

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

关键词： Crocus sativus WGT Crocin biosynthesis Carotenoids Apocarotenoids CCDs

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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern chinese Medicine Resources Chengdu University of Traditional Chinese Medicine school of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina school Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the ***,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this *** a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous ***,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention *** treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention *** the most vital component of the limbs,skeletal muscles have become potential points of *** this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal *** current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke *** addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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Efficacy and Safety of chinese Herbal Medicines Combined with Chemical Drugs for Alzheimer's Disease:A Systematic Review and Meta-Analysis

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World Journal of Traditional chinese Medicine 2024年第1期10卷 1-13页

作者： Li Xu Wen-Jun Chen Cai-Jun Tian Yan Zhang Yan Ma Tian-Hao Li Hong-Jie Liu Zhe Zhang Department of the First College English College of Foreign LanguageShandong University of Traditional Chinese MedicineJinanChina Department of Oncology Linyi People's HospitalLinyiChina Department of Internal Medicine of Traditional chinese Medicine The First Clinical CollegeShandong University of Traditional Chinese MedicineJinanChina Department of chinese materia medica College of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJinanChina Department of Medicinal Chemistry College of PharmacyShandong University of Traditional Chinese MedicineJinanChina Community Healthcare Center Shenzhen Traditional Chinese Medicine HospitalShenzhenChina Department of Fundamentals of Traditional chinese Medicine School of Traditional Chinese MedicineJinan UniversityGuangzhouChina Shandong Co-Innovation Center of Classic TCM Formula College of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJinanChina

Objective:To evaluate the efficacy and safety of chinese herbal medicines(CHMs)combined with chemical drugs for the treatment of Alzheimer's disease(AD).materials and Methods:Databases were searched to retrieve randomized controlled trials(RCTs)of CHMs combined with tacrine,galantamine,rivastigmine,donepezil,or memantine,following strict inclusion and exclusion *** research papers published in English,chinese,and Japanese were *** primary outcome was the mini-mental state examination(MMSE)score and the secondary outcomes were AD assessment scale cognitive subscale(ADAS-Cog)score and safety ***-analysis was carried out using Rev Man 5.3 and subgroup analysis was conducted to identify the sources of ***:A total of 15 RCTs with 1386 participants were included in this *** donepezil was used in the retrieved ***-analyses showed that the combination of CHMs with donepezil led to significant improvement in the MMSE score(Z=9.45;P<0.00001;weighted mean difference[WMD]=2.68,95%confidence interval[CI]:2.12-3.24)and a significant decrease in the ADAS-Cog score(Z=5.53;P<0.00001;WMD=-3.79;95%CI:-5.13--2.44).Safety evaluation demonstrated that these combination treatments relieved adverse events such as insomnia(risk ratio[RR]=0.20,95%CI:0.06-0.68;P=0.01)and hive(RR=0.10;95%CI:0.01-0.73;P=0.02).Conclusions:The combination of CHMs with a chemical drug like donepezil led to significant improvements in patient cognition as well as a better safety profile when compared to the application of a chemical drug alone.

关键词： Alzheimer's disease chinese herbal medicine donepezil memantine meta-analysis randomized controlled trials rivastigmine

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Analysis of plant resources and diversity in Shennongjia Area of Hubei Province,China

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Asian Journal of Traditional Medicines 2024年第2期19卷 66-87页

作者： Terigen Bao Min Li Jingming Jia Anhua Wang school of Traditional chinese materia medica 103 Wenhua RoadShenyang 110016China University of Michigan Ann Arbor.930 N University AveAnn ArborMI 48109USA

Shennongjia Area is located in northwest of Hubei Province with Shennongding,the highest peak(3105.4 m above sea level)in central *** unique geographical location and complex terrain of this region make it rich in plant *** field investigation,th literature review,and specimen identification,the 7 Shenyang Pharmaceutical University chinese Medicine Resources Scientific Expedition Team studied the plant resources and diversity of Shennongjia Area.454 species of vascular plants belonging to 106 families and 275 genera were collected from July to August in *** dominant families are Lamiaceae,Ranunculaceae,Rosaceae,and Asteraceae,with 20,21,37 and 48 species *** the genus level,Rubus is the dominant one with 11 species.3 species of national first-class protective plants,13 species of“Huan yang yao”and 36 species of“Qi yao”were *** all,our research has updated the plant recources and diversity in Shennongjia ***,by putting forward practical and meaningful suggestions on strengthening the protection and utilization of plant resources in Shennongjia Area,our research will help to protect the diverse ecosystem there.

关键词： plant resources diversity medicinal use Shennongjia Area

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Let-7i-5p maintains the stemness via R-spondin2/Wnt pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 20-23页

作者： Qinghua Wei Xueshan Dai Jiahui Wei Wenwei Sun Xiaoqian Yang Yuxin Zhang Xin Guo Yi Chen College of Pharmaceutical Sciences&chinese Medicine Southwest UniversityChongqing 400716China Center for Basic medical Research TEDA International Cardiovascular HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300457China Chongqing Key Laboratory of New Drug Screening from Traditional chinese Medicine Chongqing 400716China pharmacology of chinese materia medica-the Key Discipline Constructed by the State Administration of Traditional chinese Medicine Chongqing 400716China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China National Demonstration Center for Experimental Pharmacy Education(Southwest University) Chongqing 400716China Engineering Research Center of Coptis Development and Utilization(Ministry of Education) College of Pharmaceutical Sciences and Chinese MedicineSouthwest UniversityChongqing 400716China

Cancer stem cells(CSCs)are related to tumorigenesis,recurrence,metastasis,and drug resistance in hepatocellular carcinoma(HCC).1 Let-7i is a noncoding small RNA,belonging to the famous miRNA let-7 ***,let-7i has been ... 详细信息

关键词： hepatocellular Cancer metastasis

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Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou school of Traditional chinese Medicine Beijing University of Traditional Chinese MedicineBeijing102401China

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

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Scraping therapy for knee osteoarthritis: a systematic review and Meta-analysis

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Journal of Traditional chinese Medicine 2024年第4期44卷 633-641页

作者： CHEN Dandan JIN Qianhong SHEN Yuanjuan WANG Qing DAI Zhengxiang school of Nursing Guangxi University of Chinese Medicine school of Nursing Nanjing University of Chinese Medicine General Surgery Department Jiangsu Province Hospital of Chinese Medicine Hospital Infection Control Office Jiangsu Province Hospital of Chinese Medicine

OBJECTIVE: To systematically evaluate the efficacy of scraping therapy on knee osteoarthritis(KOA). METHODS: A computerized search was conducted in several databases, including PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure Database, China Science and Technology Journal Database,Wanfang, and chinese Biomedical Literature Database,from the establishment date of these databases to April 9,2023. Randomized controlled trials(RCTs) on scraping therapy for KOA were collected in accordance with the “Participants-Intervention-Control-Outcome-Study design”criteria. The methodological evaluation of the included studies was carried out using RoB 2.0, and Meta-analysis was conducted using RevMan. The Grades of Recommendations Assessment, Development and Evaluation(GRADE System) was applied to grade the quality of evidence. RESULTS: A total of 12 RCTs with 997 subjects were included in the Meta-analysis. Results indicated that compared with the control group, the scraping therapy treatment group exhibited increased Lysholm scores [mean difference(MD) = 4.96, 95% confidence intervals(CI)(3.18, 6.74), P < 0.000 01] and Hospital for Special Surgery scores [MD = 8.35, 95% CI(3.92, 12.78), P = 0.0002] and decreased visual analog scale scores [MD =-2.11, 95% CI(-3.79,-0.44), P = 0.01] and Western Ontario and McM aster University Osteoarthritis Index scores [MD =-6.77, 95% CI(-8.99,-4.56), P < 0.000 01)]. The quality of evidence obtained in this Meta-analysis was low according to the GRADE system. CONCLUSION: The available evidence suggests that scraping therapy may have certain clinical efficacy in the treatment of KOA. However, further high-quality RCTs are needed to confirm the findings.

关键词： Meta-analysis osteoarthritis, knee scraping systematic review

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SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2285-2297页

作者： Hui Qian Chen-Hong Ding Fang Liu Shi-Jie Chen Chen-Kai Huang Meng-Chao Xiao Xia-Lu Hong Ming-Chen Wang Fang-Zhi Yan Kai Ding Ya-Lu Cui Bai-Nan Zheng Jin Ding Cheng Luo Xin Zhang Wei-Fen Xie Department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Gastroenterology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Drug Discovery and Design Center CAS Key Laboratory of Receptor ResearchState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina Department of Gastroenterology First Affiliated Hospital of Nanchang UniversityNanchangChina Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghaiChina

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor ***,the precise molecular mechanisms governing the nuclear import of YAP are not fully *** this study,we have uncovered a crucial role of SOX9 in the activation of ***9 promotes the nuclear translocation of YAP by direct ***,we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of ***,we have discovered a novel asymmetrical dimethylation of YAP at Arg-124(YAP-R124me2a)catalyzed by ***-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple ***,we disrupted the interaction between SOX9 and YAP using a competitive peptide,S-A1,which mimics anα-helix of SOX9 containing Asp-125.S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor *** study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

关键词： interaction interaction precise

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Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

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World Journal of Hepatology 2024年第7期16卷 1051-1066页

作者： Xiao-Li Mei Shu-Yi Wu Si-Lan Wu Xiao-Lin Luo Si-Xing Huang Rui Liu Zhe Qiang Department of Pharmacology and Toxicology Sichuan-Chongqing Joint Key Laboratory of New Chinese Medicine Creation LaboratoryChongqing Academy of Chinese Materia MedicaChongqing 400061China College of chinese Medicine Chongqing College of Traditional Chinses MedicineChongqing 402760China Department of Oncology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China College of Pharmacy Chongqing Medical UniversityChongqing 400010China

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient ***,the molecular mechanisms underlying that remain *** To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and *** A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary *** tissues were collected for western blotting and immunohisto chemistry(IHC)*** accumulation and hepatic fibrosis were detected using oil red staining and Sirius red *** serum samples were collected for biochemical assays and NMR-based metabonomics *** inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against *** MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic *** western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of *** metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic ***,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male *** MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male *** male hormone related metabolic pathways may be the potential therapeutic app

关键词： Hepatic steatosis Inflammation Sex hormone metabolism Male hormone Phosphatase and tensin homolog deleted on chromosome ten

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A kinetic resolution accompanied chirality transformation process for asymmetric synthesis of chiral phenol,oxaziridine,and α-hydroxyl cyclic ketone

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Science China Chemistry 2024年

作者： Pengxin Wang Xiaoyong Zhang Lingqing Wang Rui Wang Dongxu Yang Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences & Research Unit of Peptide ScienceChinese Academy of Medical Sciences Lanzhou University State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College school of Sciences Great Bay University Institute of Systems and Physical Biology Shenzhen Bay Laboratory

Chirality transformation is a basic, attractive, and important strategy for obtaining enantioenriched products with desired chiral elements. The reported chirality conversion reaction often involves the process from one type of chirality to another one. To better utilize the chirality transformation strategy for obtaining two or more products with different chiral elements in a single reaction, a new method of kinetic resolution accompanied by a chirality transformation protocol is proposed and successfully realized in this study. This process is used for the asymmetric oxidation of phenol compounds along with the kinetic resolution of oxaziridines. A wide scope of products, including axially chiral phenols, oxaziridines, and α-hydroxyl cyclic ketones were smoothly obtained in high levels of yields and enantioselectivities in the developed method. These products can be readily used for the synthesis of various types of chiral ligands, which are potential choices for other catalytic asymmetric reactions.

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