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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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Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia

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traditional medicine Research 2024年第11期9卷 12-26页

作者： Jie-Hui Kuang Tao Hu Lu-Yong Zhang Yu-Feng Yao Ming-Hua Xian Shu-Mei Wang School of chinese Materia Medica Guangdong Pharmaceutical UniversityGuangzhou 510006China Key Laboratory of Digital Quality Evaluation of chinese Materia Medica of State administration of traditional chinese medicine Guangdong Pharmaceutical UniversityGuangzhou 510006China Engineering&Technology Research center for chinese Materia Medica Quality of the Universities of Guangdong Province Guangdong Pharmaceutical UniversityGuangzhou 510006China Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems Guangdong Pharmaceutical UniversityGuangzhou 510006China traditional chinese medicine Resource Germplasm Bank Management center Yunfu 527500China.

Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac ***,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic *** objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat ***:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of *** integration of network pharmacology and metabolomics was conducted to investigate the *** docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated ***:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart *** results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for *** network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl ***:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.

关键词： chronic myocardial ischemia metabolomics network pharmacology serum metabolites Shenzao dripping pill

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Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

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chinese Journal of Natural medicines 2024年第5期22卷 402-415页

作者： XIU Ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan ZOU Liang XIAO Xiaohe BAI Zhaofang School of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China national Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and *** this,the clinical approval of drugs targeting the cGAS-STING pathway has been *** Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our *** found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku Hospital Pediatrics-1(THP-1)*** inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling *** vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor

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Abelmoschus manihot polysaccharide fortifies intestinal mucus barrier to alleviate intestinal inflammation by modulating Akkermansia muciniphila abundance

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3901-3915页

作者： Yumeng Wang Chengxi Li Jianping Li Shu Zhang Qinyu Zhang Jinao Duan Jianming Guo Jiangsu Collaborative Innovation center of chinese Medicinal Resources Industrialization Nanjing University of Chinese MedicineNanjing 210023China Jiangsu Key Laboratory for High Technology Research of TCM Formulae Nanjing University of Chinese MedicineNanjing 210023China

The intestinal mucus barrier is an important line of defense against gut *** to this barrier brings bacteria into close contact with the epithelium,leading to intestinal ***,its restoration is a promising strategy for alleviating intestinal *** study showed that Abelmoschus manihot polysaccharide(AMP)fortifies the intestinal mucus barrier by increasing mucus production,which plays a crucial role in the AMP-mediated amelioration of ***-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on ***,bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia *** findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut *** demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

关键词： Plant polysaccharide Abelmoschus manihot Intestinal inflammation Mucus barrier Interleukin 10 Gut microbiota A.muciniphila Mucin 2

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Treatment of lumbar disc herniation with robot combined with unilateral biportal endoscopic technology:A case report

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World Journal of Clinical Cases 2024年第17期12卷 3235-3242页

作者： Yan-Dong Liu Duo-Fang Xu Qiang Deng Yan-Jun Zhang Tie-Feng Guo Ran-Dong Peng Jun-Jie Li Graduate School Gansu University of Traditional Chinese MedicineLanzhou 730030Gansu ProvinceChina Spinal Disease Treatment center Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050Gansu ProvinceChina Department of Spinal Orthopedics II Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050Gansu ProvinceChina Department of Osteomyelitis Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050Gansu ProvinceChina

BACKGROUND This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion(UBE-LIF),utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment,and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw *** advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies,and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients,and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for *** SUMMARY A 44-year-old patient presented to our *** various clinical data,we diagnosed the patient with lumbar disc herniation with radiculopathy,lumbar spondylolisthesis,and lumbar spinal *** developed a surgical plan of"UBE decompression+UBE-LIF+orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation".The results were *** We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good ***,the technique is worthy of clinical promotion.

关键词： Orthopedic robot Unilateral biportal endoscopy Unilateral biportal endoscopic lumbar interbody fusion Lumbar disc herniation Decompression fusion Case report

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Effects of plants-associated microbiota on cultivation and quality of chinese herbal medicines

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chinese Herbal medicines 2024年第2期16卷 190-203页

作者： Yue Ouyang Qiqing Cheng Chunsong Cheng Ziyu Tang Yufeng Huang Eyu Tan Shaofeng Ma Xinheng Lin Ying Xie Hua Zhou Guangdong Provincial Hospital of chinese medicine Guangdong Provincial Academy of Chinese Medical SciencesState Key Laboratory of Dampness Syndrome of Chinese MedicineSecond Affiliated Hospital of Guangzhou University of Chinese MedicineGuangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease ResearchGuangzhou 510006China Faculty of chinese medicine Macao University of Science and TechnologyMacao 999078China School of Pharmacy Hubei University of Science and TechnologyXianning 437100China Key Laboratory of Plant Ex-situ Conservation and Research center of Resource Plant Lushan Botanical GardenChinese Academy of SciencesJiujiang 332900China Jiangmen Wuyi Hospital of traditional chinese medicine Jiangmen 529020China Joint Laboratory for Translational Cancer Research of chinese medicine Ministry of EducationGuangzhou University of Chinese MedicineGuangzhou 510006China

Microbial resource influences the life activities of medicinal plants from several ***,rhizosphere microorganisms,and other environmental microorganisms play essential roles in medicinal plant growth and development,plant yield,and clinical *** microbiota can influence the biosynthesis of active compounds in medicinal plants by stimulating specific metabolic *** induce host plants to improve their resistance to environmental stresses by accumulating secondary *** can interact with their host plants to produce long-term,targeted selection results and improve their ability to adapt to the *** to the interdependence and interaction between microorganisms and medicinal plants,chinese herbal medicines(CHMs)quality is closely related to the associated *** review summarizes the relationship between medicinal plants and their associated microorganisms,including their species,distribution,life activities,and *** can aid in quality control,improve the efficacy of medicinal plants,and provide markers for identifying the origin and storage time of ***,a comprehensive understanding of the relationship between microorganisms and medicinal plants will help to control the quality of CHMs from different perspectives.

关键词： chinese herbal medicines endophytes environmental microorganisms microbiota rhizosphere microorganisms

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Research Progress on the Bone Metastasis Mechanism of Prostate Cancer and Bone-Targeted Drugs

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Proceedings of Anticancer Research 2024年第4期8卷 30-34页

作者： Xiaoqing Zhang Bifeng Fu Ruiyu Mu Chunxin Jia Jiayu Li Haibo Xie Si Wu Ping Wang Aifeng Liu Guang Yang Xingyu Jiang Department of Orthopedics and Traumatology First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300381China Department of Oncology First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300381China national Clinical Research center for chinese medicine Acupuncture and Moxibustion Tianjin 300381China

Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate *** mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and *** recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone *** on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research.

关键词： Prostate cancer Bone metastasis Mechanism Bone targeting drugs Cancer cell

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Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave:a single-center cohort study

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 529-540页

作者： Duo LV Xishao XIE Qinyun YANG Zhimin CHEN Guangjun LIU Wenhan PENG Rending WANG Hongfeng HUANG Jianghua CHEN Jianyong WU Department of Clinical Pharmacy the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research Hangzhou 310003China Kidney Disease center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Kidney Disease Prevention and Control Technology Zhejiang ProvinceHangzhou 310003China Institute of Nephrology Zhejiang UniversityHangzhou 310003China Zhejiang Clinical Research center of Kidney and Urinary System Disease Hangzhou 310003China The Third Grade Laboratory under the national State Administration of Traditional Chinese MedicineHangzhou 310003China Information center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are ***:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,*** patients were followed up until Mar.31,***:A total of 324 KTRs with COVID-19 were *** median age was 49 *** median time between the onset of symptoms and admission was 13 ***,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,***-nine(9.0%)patients were treated with more than one antiviral ***-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib *** acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care *** infections were observed in 55(17.0%)***(15.4%)patients lost their *** 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of *** Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized ***:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of *** administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.

关键词： Coronavirus disease 2019(COVID-19) Kidney transplant Hospitalization Mortality

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A non-viral gene therapy for melanoma by staphylococcal enterotoxin A

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chinese Chemical Letters 2024年第5期35卷 325-329页

作者： Ling Yang Min Ren Jie Wang Liming He Shanshan Wu Shuai Yang Wei Zhao Hao Cheng Xiaoming Zhou Maling Gou State Key Laboratory of Biotherapy and Cancer center West China HospitalSichuan UniversityChengdu 610041China Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Biotherapy Department of Integrated Traditional Chinese and Western MedicineRare Diseases CenterWest China HospitalSichuan UniversityChengdu 610041China

Staphylococcal enterotoxin A(SEA)derived from Staphylococcus aureus,as a superantigen,shows potential for cancer immunotherapy,but systemic immunotoxicity restricts its clinical *** delivery of SEA to tumor site provides a promising option for reducing the systemic ***,we constructed an iRGD peptide(H-[Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys]-NH_(2))modified nanoparticle(iDPP)to deliver plasmids encoding SEA for melanoma *** iDPP/SEA nanocomplexes efficiently mediated SEA expression in B16-F10 cells in vivo and in vitro and induced the activation of lymphocytes and maturation of murine bone marrow-derived dendritic cells(BMDCs)in *** the subcutaneous B16-F10 melanoma model,the iDPP/SEA nanocomplexes could effectively enhance immune response and T lymphocytes infiltration in tumor site after intravenous administration,thereby considerably decreased melanoma ***,no obvious adverse effect was observed after intravenous administration of the iDPP/SEA nanocomplexes in *** findings demonstrated that gene therapy of SEA is a potential candidate for melanoma treatment.

关键词： Gene therapy Superantigen Melanoma Staphylococcal enterotoxins A Immunotherapyene therapy

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Recombinant adeno-associated virus 8 vector in gene therapy:Opportunities and challenges

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Genes & Diseases 2024年第1期11卷 283-293页

作者： Liyuan Zhao Zixuan Yang Minhui Zheng Lei Shi Mengyun Gu Gang Liu Feng Miao Yan Chang Fanghua Huang Naping Tang Anhui University of traditional chinese medicine HefeiAnhui 230000China Yangtze Delta Drug Advanced Research Institute Yangtze Delta Pharmaceutical CollegeNantongJiangsu226133China Shanghai Innostar Bio-Technology Co. LtdChina State Institute of Pharmaceutical IndustryShanghai 201203China Innostar Bio-tech Nantong Co. Ltd.NantongJiangsu 226133China center for Drug Evaluation National Medical Products AdministrationBeijing 100022China

In recent years,significant breakthroughs have been made in the field of gene ***-associated virus(AAV)is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of *** the AAV vectors,AAV serotype 8(AAv8)has attracted much attention for its efficient and stable gene transfection into specific ***,recombinant AAv8 has been widely used in gene therapy research on a va-riety of diseases,including genetic diseases,cancers,autoimmune diseases,and viral diseases.

关键词： AAV8 Adeno-associated virus Gene therapy Primates

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