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Strategies and opportunities of micro/nano delivery systems for targeted therapy of ulcerative colitis:Focus on underlying mechanisms and future perspectives

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Chinese Chemical Letters 2024年第2期35卷 118-130页

作者： Zihan Liu Han Liu Jialing Cheng Hongliang Wang Yanfang Yang Jun Ye Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing 100050China

Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe *** are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse *** the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient *** this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating ***,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of *** but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.

关键词： Ulcerative colitis Physiological characteristics Colon-specific drug delivery Mechanisms of action Targeted therapy of UC

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Advancements in precision nanomedicine design targeting the anoikis-platelet interface of circulating tumor cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3457-3475页

作者： Manqing Tang Zhijie Zhang Ping Wang Feng Zhao Lin Miao Yuming Wang Yingpeng Li Yunfei Li Zhonggao Gao College of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of Component-Based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Tumor metastasis,the apex of cancer progression,poses a formidable challenge in therapeutic *** tumor cells(CTCs),resilient entities originating from primary tumors or their metastases,significantly contribute to this process by demonstrating remarkable *** survive shear stress,resist anoikis,evade immune surveillance,and thwart *** comprehensive review aims to elucidate the intricate landscape of CTC formation,metastatic mechanisms,and the myriad factors influencing their *** signaling pathways,such as integrin-related signaling,cellular autophagy,epithelial-mesenchymal transition,and interactions with platelets,are examined in ***,we explore the realm of precision nanomedicine design,with a specific emphasis on the anoikis‒platelet *** innovative approach strategically targets CTC survival mechanisms,offering promising avenues for combatting metastatic cancer with unprecedented precision and *** review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.

关键词： CTCs Anoikis Platelet Cancer stem cell Metastasis Platelet‒CTC interaction Platelet targeting Nanomedicines

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CRISPR-Cas9-based genome-editing technologies in engineering bacteria for the production of plant-derived terpenoids

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Engineering Microbiology 2024年第3期4卷 43-53页

作者： Xin Sun Haobin Zhang Yuping Jia Jingyi Li Meirong Jia State Key Laboratory of Bioactive Substance and Function of Natural Medicines NHC Key Laboratory of Biosynthesis of Natural ProductsCAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Shandong Academy of Pharmaceutical Sciences Jinan 250101China

Terpenoids are widely used as medicines,flavors,and ***,the use of these natural products is largely restricted by their low abundance in native ***,heterologous biosynthesis of terpenoids in microorganisms offers an alternative and sustainable approach for efficient *** genome-editing technologies have been developed for microbial strain *** regularly interspaced short palin-dromic repeats(CRISPR)-CRISPR associated protein 9(Cas9)is the most commonly used system owing to its outstanding efficiency and convenience in genome *** this review,the basic principles of CRISPR-Cas9 systems are briefly introduced and their applications in engineering bacteria for the production of plant-derived terpenoids are *** aim of this review is to provide an overview of the current developments of CRISPR-Cas9-based genome-editing technologies in bacterial engineering,concluding with perspectives on the challenges and opportunities of these technologies.

关键词： CRISPR-Cas9 Genome editing Terpenoids Metabolic engineering Bacteria

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Two unique C21-diterpenoid alkaloids from Aconitum carmichaelii

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Chinese Chemical Letters 2022年第12期33卷 5047-5050页

作者： Jingfang Zhang Xiaoqiang Lei Yazi Wei Hui Liu Qinglan Guo Tiantai Zhang Jiangong Shi State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Two sulfonated diterpenoid alkaloids possessing different but related novel carbon skeletons,named aconidenusulfonine A(1)and 12,16-secoaconidenusulfonine A(2),respectively,were isolated as minor components from an aqueous extract of the lateral roots of Aconitum carmichaelii("Fu Zi").The structures of 1 and 2,representing the first two C21-diterpenoid alkaloids from nature,were determined by analysis of various spectroscopic data and chemical transformation,of which 1 was further proved by single-crystal X-ray ***,1 exhibited dose-depended analgesic activity consistent with the clinical function of Fu Zi.

关键词： Ranunculaceae Aconitum carmichaelii C21-diterpenoid alkaloid Aconidenusulfonine Analgesic activity

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Arnequinol A and arnequinone A, two unique meroterpenoids from Arnebia euchroma

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Chinese Chemical Letters 2022年第5期33卷 2555-2558页

作者： Hai-Wei Yan Rong-Rong Du Xu Zhang Ya-Nan Yang Xiang Yuan Zi-Ming Feng Jian-Shuang Jiang Pei-Cheng Zhang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Arnequinol A(1),featuring an unprecedented 6/6/3 tricyclic carbon skeleton fused with a heptatomic oxo-bridge,together with arnequinone A(2)bearing a highly conjugated methyl-shifting benzogeijerene skeleton,were isolated from Arnebia *** structures were elucidated by extensive spectro-scopic methods and quantum chemical calculations of the 13 C nuclear magnetic resonance(NMR)data and electronic circular dichroism(ECD)*** plausible biosynthetic pathways for 1 and 2 were *** in vitro test,compound 2 showed potent neuroprotective activity against serum-deprivation induced PC12 cell damage at a concentration of 10μmol/L.

关键词： Arnebia euchroma Meroterpenoids Arnequinol A and arnequinone A Cytotoxicity Neuroprotective activity

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Regulatory T cells in ischemic stroke

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中国药理学报（英文版） 2022年第1期43卷 1-9页

作者： Hong-yun Wang Jun-rui Ye Li-yuan Cui Shi-feng Chu Nai-hong Chen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica and Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Recent evidence shows that when ischemic stroke(IS)occurs,the BBB would be destructed,thereby promoting the immune cells to migrate into the brain,suggesting that the immune responses can play a vital role in the pathology of *** an essential subpopulation of immunosuppressive T cells,regulatory T(Treg)cells are involved in maintaining immune homeostasis and suppressing immune responses in the pathophysiological conditions of *** the past decades,the regulatory role of Treg cells has attracted the interest of numerous ***,whether they are beneficial or detrimental to the outcomes of IS remains ***,Treg cells exert distinctive effects in the different stages of ***,it is urgent to elucidate how Treg cells modulate the immune responses induced by *** this review,we describe how Treg cells fluctuate and play a role in the regulation of immune responses after IS in both experimental animals and humans,and summarize their biological functions and mechanisms in both CNS and *** also discuss how Treg cells participate in poststroke inflammation and immunodepression and the potential of Treg cells as a novel therapeutic approach.

关键词： regulatory T cells ischemic stroke inflammation crosstalk stroke-induced immunodepression ischemic stroke therapy

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New advances of adiponectin in regulating obesity and related metabolic syndromes

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Journal of Pharmaceutical Analysis 2024年第5期14卷 623-638页

作者： Yanqi Han Qianwen Sun Wei Chen Yue Gao Jun Ye Yanmin Chen Tingting Wang Lili Gao Yuling Liu Yanfang Yang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking UnionMedical CollegeBeijing100050China Beijing Key Laboratoryof Drug Delivery Technology and NovelFormulation Institute of Materia MedicaChinese Academyof Medical Sciences&Peking UnionMedical CollegeBeijing100050China

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ***(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue *** on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain ***,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP *** modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic *** order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

关键词： Adiponectin Obesity Metabolic syndrome Regulation

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Target fishing and mechanistic insights of the natural anticancer drug candidate chlorogenic acid

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Acta Pharmaceutica Sinica B 2024年第10期14卷 4431-4442页

作者： Qinghua Wang Tingting Du Zhihui Zhang Qingyang Zhang Jie Zhang Wenbin Li Jian-Dong Jiang Xiaoguang Chen Hai-Yu Hu State Key Laboratory of Bioactive Substances and Function of Natural Medicine Beijing Key Laboratory of Active Substances Discovery and Drugability EvaluationInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Sichuan Jiuzhang Biological Science and Technology Co. Ltd.Chengdu 610041China Cancer Center Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China

Chlorogenic acid(CGA)is a natural product that effectively inhibits tumor growth,demonstrated in many preclinical models,and phase II clinical trials for patients with ***,its direct proteomic targets and anticancer molecular mechanisms remain ***,we developed a novel bi-functional photo-affinity probe PAL/CGA and discovered mitochondrial acetyl-CoA acetyltransferase 1(ACAT1)was one of the main target proteins of CGA by using affinity-based protein profiling(AfBPP)chemical proteomic *** performed in-depth studies on ACAT1/CGA interactions via multiple assays including SPR,ITC,and ***,we demonstrated that CGA impaired cancer cell proliferation by inhibiting the phosphorylation of tetrameric ACAT1 on Y407 residue through a novel mode of action in vitro and in *** study highlights the use of AfBPP platforms in uncovering unique druggable modalities accessed by natural *** identifying the molecular target of CGA sheds light on the future clinical application of CGA for cancer therapy.

关键词： AfBPP natural product Chlorogenic acid Probe ACAT1

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Unlocking the potential of amorphous calcium carbonate: A star ascending in the realm of biomedical application

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Acta Pharmaceutica Sinica B 2024年第2期14卷 602-622页

作者： Han Liu Zhiyang Wen Zihan Liu Yanfang Yang Hongliang Wang Xuejun Xia Jun Ye Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and ***-based materials can also deliver contrast agents,which can enhance real-time imaging and exert a Ca^(2+)-interfering therapeutic *** on these characteristics,amorphous calcium carbonate(ACC),as a brunch of calcium-based biomaterials,has the potential to become a widely used *** functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However,the standalone presence of ACC is unstable in *** are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its *** has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo,such as Ca^(2+) with an immune-regulating ability and CO_(2) with an imaging-enhancing *** to these characteristics,ACC has been studied for selfsacrificing templates of carrier construction,targeted delivery of oncology drugs,immunomodulation,tumor imaging,tissue engineering,and calcium *** in this paper has been placed on the origin,structural features,and multiple applications of ***,ACC faces many challenges in clinical translation,and long-term basic research is required to overcome these *** hope that this study will contribute to future innovative research on ACC.

关键词： Amorphous calcium carbonate Drugdelivery system Nanoparticle Acid sensitivity Water instability,Tumortherapy Tissue engineering Calcium supplement

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(+)/(-)-Yanhusamides A-C,three pairs of unprecedented benzylisoquinoline-pyrrole hetero-dimeric alkaloid enantiomers from Corydalis yanhusuo

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Acta Pharmaceutica Sinica B 2023年第2期13卷 754-764页

作者： Lingyan Wang Guiyang Xia Huan Xia Xiaohong Wei Yanan Wang Sheng Lin Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids,(+)/(-)-yanhusamides A-C(1-3),featuring an unprecedented 3,8-diazatricylco[5.2.2.0^(2,6)]undecane-8,10-diene bridged *** structures were exhaustively characterized by X-ray diffraction,comprehensive spectroscopic data analysis,and computational *** by the hypothetical biosynthetic pathway for 1-3,a gram-scale biomimetic synthesis of(±)-1 was achieved in 3 steps using photoenolization/Diels-Alder(PEDA)[4+2]*** 1-3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 *** in vivo assay showed that oral administration of 30 mg/kg of(±)-1 attenuated the severity of rat adjuvant-induced arthritis(AIA).Additionally,(±)-1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.

关键词： (+)/(-)-Yanhusamides A-C Hetero-dimeric alkaloids Corydalis yanhusuo Anti-inflammatory Analgesic activity

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