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Research progress on natural products against hepatocellular carcinoma

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BIOCELL 2024年第6期48卷 905-922页

作者： LINGLI ZHANG YAN LI JINGXIN MAO Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System Chongqing Medical and Pharmaceutical CollegeChongqing400030China Provincial Key Laboratory of Pharmaceutical Bioactive Substances School of Life Sciences and BiopharmaceuticalsGuangdong Pharmaceutical UniversityGuangzhou510006China

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable *** the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering signiﬁcant *** integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of *** review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC ***,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC *** products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

关键词： Hepatocellular carcinoma Natural products Targets Research progress Drug

Populational change of CD4^(+)CD25^(+)Treg cells is responsible for the synergistic effect of the combination of RAMP2 with baicalin in treating recurrent spontaneous abortion mouse models

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Traditional Medicine Research 2024年第8期9卷 59-66页

作者： Cong Chen Zhuo-Lan Li Jing-Tian Guo Wen-Yao Xue Wei Guo Department of Gynecology Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China Jiangsu Key Laboratory of Druggability of biopharmaceuticals State Key Laboratory of Natural MedicinesSchool of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198China

Background: The absence of a safe and effective therapy for recurrent spontaneous abortion due to a maternofetal failure in immunological tolerance remains an intractable clinical obstacle for surgeons. Recently, traditional Chinese medicine has become a feasible alternative for certain diseases, including recurrent spontaneous abortion. However, because of the complex composition of the traditional Chinese medicine formula, its action mechanism remains unclear. Methods: We selected two isolated active ingredients (RAMP and baicalin) from the traditional Chinese medicine formula and used an abortion-prone CBA/J × DBA/2 model to simulate human RSA and compared the changes in fetal resorption rate, Treg cell percentage, and relevant cytokines before and after combination therapy. In addition, The mechanisms were preliminarily discussed using in vitro differentiation models. Results: In CBA/J × DBA/2 abortion-prone mice, the combination therapy resulted in a lower embryo resorption rate compared to that obtained with individual delivery of either RAMP or baicalin, thereby playing an embryo-protective role through the increase in Treg cells for the maintenance of maternal-fetal immune tolerance. In in vitro primary cell differentiation experiments, the concentration of Treg cells significantly increased from 11% to 17.9% after the combination therapy compared to that of the single administration group. Conclusion: the synergistic effects of RAMP and baicalin were responsible for Treg differentiation. The present study provides a solid basis for improving the applicability of traditional Chinese herbs in the treatment of recurrent spontaneous abortion.

关键词： recurrent spontaneous abortion Atractylodes macrocephala Koidz. Scutellaria baicalensis Georgi CBA/J×DBA/2 regulatory T cells

Recent advances in essential oils and their nanoformulations for poultry feed

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Journal of Animal Science and Biotechnology 2024年第5期15卷 1802-1819页

作者： Fatemeh Movahedi Nilesh Nirmal Pengyuan Wang Hongping Jin Lisbeth Grondahl Li Li Australian Institute for Bioengineering and Nanotechnology The University of QueenslandBrisbaneQLD 4072Australia Institute of Nutrition Mahidol University999 Phutthamonthon 4 RoadSalayaNakhon Pathom 73170Thailand Oujiang Laboratory Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhou 325000ZhejiangChina JECHO biopharmaceuticals Co. Ltd.No.2633Zhongbin AvenueSino‑Singapore Tianjin Eco‑cityBinhai New AreaTianjinChina School of Chemistry and Molecular Biosciences The University of QueenslandBrisbaneQLD 4072Australia

Antibiotics in poultry feed to boost growth performance are becoming increasingly contentious due to concerns over antimicrobial resistance *** oils(EOs),as natural,plant-derived compounds,have demonstrated antimicrobial and antioxidant *** may potentially improve poultry health and growth performance when included in poultry ***,the incorporation of EOs as nutritional additives is hindered by their high volatility,low water solubility,poor intestinal absorption,and sensitivity to environmental ***,nanoencapsulation strategies using nanoformulations have emerged as a potential solution to these challenges,improving the stability and bioavailability of EOs,and enabling targeted delivery in poultry *** review provides an overview of the antioxidant and antibacterial properties of EOs,the current limitations of their applications in poultry feed,and the recent advancements in nano-engineering to overcome these ***,we outline the potential future research direction on EO nanoformulations,emphasizing their promising role in advancing sustainable poultry nutrition.

关键词： Antibacterial activities Antioxidants Essential oils Nanoformulations Poultry additives

In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides

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Journal of Pharmaceutical Analysis 2024年第6期14卷 840-850页

作者： Zhenjie Yu Huarong Shao Xintian Shao Linyan Yu Yanan Gao Youxiao Ren Fei Liu Caicai Meng Peixue Ling Qixin Chen Key Laboratory for Biotechnology Drugs of National Health Commission School of Pharmaceutical Sciences&Institute of Materia MedicaMedical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan250117China Key Laboratory of biopharmaceuticals Engineering Laboratory of Polysaccharide DrugsNational-Local Joint Engineering Laboratory of Polysaccharide DrugsShandong Academy of Pharmaceutical ScienceJinan250101China Shenzhen Research Institute of Xiamen University ShenzhenGuangdong518057China School of Life Sciences Medical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan250117China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and Faculty of EngineeringNational University of SingaporeSingapore119074Singapore School of Pharmaceutical Sciences Shandong UniversityJinan250101China

Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and *** address this issue,we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of *** a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured *** recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the ***,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid *** drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related ***,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)^(-/-)mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and ***,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug ***,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with medicinal effects.

关键词： Cellular imaging Fluorescence labeling Mussel oligosaccharide Lipid metabolism

A preparation strategy for protein-oriented immobilized silica magnetic beads with Spy chemistry for ligand fishing

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Journal of Pharmaceutical Analysis 2022年第3期12卷 415-423页

作者： Yu Yi Jianming Hu Shenwei Ding Jianfeng Mei Xudong Wang Yanlu Zhang Jianshu Chen Guoqing Ying Institute of biopharmaceuticals College of Pharmaceutical ScienceZhejiang University of TechnologyHangzhou310014China

Due to the complexity of bioactive ingredients in biological samples,the screening of target proteins is a complex ***,a feasible strategy for directing protein immobilization on silica magnetic beads for ligand fishing based on SpyTag/SpyCatcher(ST/SC)-mediated anchoring is *** functional groups on the surface of silica-coated magnetic beads(SMBs)were coupled with SC using the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide method,named *** green fluorescent protein(GFP),as the capturing protein model,was ST-labeled and anchored at a specific orientation onto the surface of SC-SMBs directly from relevant cell lysates via ST/SC *** characteristics of the SC-SMBs were studied via electron microscopy,energy dispersive spectroscopy,and Fourier transform infrared *** spontaneity and site-specificity of this unique reaction were confirmed via electrophoresis and fluorescence *** the alkaline stability of ST-GFP-ligated SC-SMBs was not ideal,the formed isopeptide bond was unbreakable under acidic conditions(0.05 M glycine-HCl buffer,pH 1e6)for 2 h,under 20%ethanol solution within 7 days,and at most ***,therefore,present a simple and universal strategy for the preparation of diverse protein-functionalized SMBs for ligand fishing,prompting its usage on drug screening and target finding.

关键词： EDC/Sulfo-NHS SpyTag/SpyCatcher Green fluorescent protein Silica magnetic beads Oriented immobilization Drug screening

B7-H7 (HHLA2) inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling

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Cellular & Molecular Immunology 2021年第6期18卷 1503-1511页

作者： Sadiye Amcaoglu Rieder Jingya Wang Natalie White Ariful Qadri Catherine Menard Geoffrey Stephens Jodi LKarnell Christopher ERudd Roland Kolbeck Present address:Viela Bio GaithersburgMDUSA Universite de Montreal MontrealQCCanada MedImmune/AstraZeneca GaithersburgMDUSA biopharmaceuticals Early RIAAstraZenecaGaithersburgMDUSA biopharmaceuticals Early RIAAstraZenecaGaithersburgMDUSA View author publications

Modulation of T-cell responses has played a key role in treating cancers and autoimmune ***,understanding how different receptors on T cells impact functional outcomes is *** influence of B7-H7(HHLA2)and CD28H(TMIGD2)on T-cell activation remains *** we examined global transcriptomic changes in human T cells induced by *** through TCR with OKT3 and B7-H7 resulted in modest fold changes in the expression of select genes;however,these fold changes were significantly lower than those induced by OKT3 and B7-1 *** transcriptional changes induced by OKT3 and B7-H7 were insufficient to provide functional stimulation as measured by evaluating T-cell proliferation and cytokine ***,B7-H7 was coinhibitory when simultaneously combined with TCR and CD28 *** inhibitory activity was comparable to that observed with ***,in physiological assays using T cells and APCs,blockade of B7-H7 enhanced T-cell activation and proliferation,demonstrating that this ligand acts as a break *** work defines that the transcriptomic changes induced by B7-H7 are insufficient to support full costimulation with TCR signaling and,instead,B7-H7 inhibits T-cell activation and proliferation in the presence of TCR and CD28 signaling.

关键词： T cell inhibition Checkpoint pathway T cell transcriptomics

Transposon-based screen identifies a XRE family regulator crucial for candicidin biosynthesis in Streptomyces albus J1074

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Science China(Life Sciences) 2020年第9期63卷 1421-1424页

作者： Jun Tian Leixin Ye Yuling Yang Yalin Zhang Changhua Hu Guojian Liao Institute of Modern biopharmaceuticals College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China

Dear Editor,Polyene macrolides are a group of natural products with potent antifungal activity (Caffrey et al., 2016). Candicidin/FR-008, a potent broad-spectrum anti-fungal agent, is produced by several Streptomycetes, including Streptomycetes sp. strain FR-008 (Chen et al., 2003), S. griseus 3570(Campelo and Gil, 2002) and S. albus J1074 (Olano et al.,2014). Due to its medical importance, considerable effort has been applied to elucidate its biosynthetic pathway and identify key regulatory genes (Chen et al., 2003;Zhang et al.,2015).

关键词： agent cidin identif

The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair

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Cellular & Molecular Immunology 2023年第6期20卷 570-582页

作者： Chiara Giacomini Ceilia Graneli Ryan Hicks Francesco Dazzi School of Cardiovascular and Metabolic Medicine&Sciences King's College LondonLondonUK biopharmaceuticals R&D Cell Therapy Department Research and Early DevelopmentCardiovascularRenaland Metabolism(CVRM)BioPharmaceuticals R&DAstraZenecaGothenburgSweden

Mesenchymal stromal cells(MsCs)have been extensively tested for the treatment of numerous clinical conditions and have demonstrated good safety but mixed *** this outcome can be attributed in part to the heterogeneity of cell preparations,the lack of mechanistic understanding and tools to establish cell pharmacokinetics and pharmacodynamics,as well as the poorly defined criteria for patient stratification,have hampered the design of informative clinical *** and others have demonstrated that MsCs can rapidly undergo apoptosis after their *** MSCs are phagocytosed by monocytes/macrophages that are then reprogrammed to become anti-inflammatory *** apoptosis occurs when the cells are injected into patients who harbor activated cytotoxic T or NK ***,the activation state of cytotoxic T or NK cells can be used as a biomarker to predict clinical responses to MsC *** on a large body of preexisting data,an alternative view on the mechanism of MSCs is that an inflammation-dependent MSC secretome is largely responsible for their immunomodulatory *** will discuss how these different mechanisms can coexist and are instructed by two different types of Msc"licensing":one that is cell-contact dependent and the second that is mediated by inflammatory *** varied and complex mechanisms by which MsCs can orchestrate inflammatory responses and how this function is specifically driven by inflammation support a physiological role for tissue stroma in tissue homeostasis,and it acts as a sensor of damage and initiator of tissue repair by reprogramming the inflammatory environment.

关键词： Mesenchymal stromal cells Cell death immunosuppression

Discovery and characterization of novel potent non-covalent small molecule inhibitors targeting papain-like protease from SARS-CoV-2

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3286-3290页

作者： Miao Zheng Bo Feng Yumin Zhang Xin Liu NaZhao Hui Liu Zichao Xu Xinheng He Zhiyan Qu ShizhaoChen Zhidong Jiang Xi Cheng Hong Liu Yi Zang Linxiang Zhao Jie Zheng Leike Zhang Jia Li Yu Zhou Key Laboratory of Structure-Based Drugs Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Sciences and biopharmaceuticals Shenyang Pharmaceutical UniversityShenyang 110016China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203and University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Chemical Biology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203and University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China Lingang Laboratory Shanghai 200031China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Hubei Jiangxia Laboratory Wuhan 430200China

To the Editor:The papain-like protease(PL^(pro)),as one of the most important proteases of SARS-CoV-2,has emerged as a highly promising target protein,its inhibitor probably holds dual potentials,namely blocking the cleavage of viral polyprotein and intercepting the deubiquitination and deISGylation functions to restore antiviral immunity1.

关键词： Non-covalent PL^(pro)inhibitors Antiviral activity Structural-based drug design Imidazo[4,5-b]pyridine scaffold