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Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membranedecorated nanoparticles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3218-3231页

作者： Wen Zhang Yihui Zhai Ying Cai Xiang Gong Yunxuan Jiang Rong Rong Chao Zheng Binyu Zhu Helen He Zhu Hao Wang Yaping Li Pengcheng Zhang China State institute of Pharmaceutical Industry Shanghai 201203China State Key Laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Biomedical Engineering&State Key Laboratory of Advanced medical materials and Devices ShanghaiTech UniversityShanghai 201210China School of Chinese materia medica Nanjing University of Chinese MedicineNanjing 210023China Yantai institute of materia medica Shandong 264000China State Key Laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127China University of Chinese Academy of Sciences Beijing 100049China

Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocompatibility complex I(MHC-I)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-I-deficient *** on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer *** released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 *** also block CD47-mediated phagocytosis *** inhibit the growth of MHC-I-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important *** macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophagemediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

关键词： MHC-I deficiency Macrophage CD47 Immunotherapy Triple-negative breast cancer Phagocytosis Immune checkpoint Innate immunity

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TCP-1,a novel peptide to diagnose early colon cancer

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Chinese Chemical Letters 2024年第3期35卷 226-233页

作者： Hang Yu Baoying Wen Min Huang Ru Feng Libin Pan Manyi Xu Hao Lin Lin Cong Sen Zhang Yan Li Chi-Hin Cho Chongjing Zhang Xiaoguang Chen Yan Wang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesBeijing 100050China School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina

A nine cyclic peptide(TCP-1)showed excellent specificity for colon ***-1 binds with human tumor tissues at early stages and mice tumor with diameters of 1-4 mm,suggesting that TCP-1 may be used for early diagnosis of colon *** mechanism of the targeted binding of TCP-1 to colon cancer was also studied using immunoprecipitation,LC-MS and *** screening and identifying of the possible binding target proteins of TCP-1,keratin,typeⅡcytoskeletal 5 was speculated to be the specific binding target protein of TCP-1 in human tumor *** studies were conducted to investigate the target-mediated drug disposition of the new tumor-specific peptide by LC-MS/*** tissue distribution study showed that TCP-1 was found only in colon tumors(the target site)in tumor mice did not bind to any other *** TCP-1 to tumor markedly increased its removal rate from blood circulation but mildly extended its staying time in *** tumor mice,a lower AUC of TCP-1(reduced by almost 35%)and 2-fold higher clearance were found compared to that of normal *** proposed metabolic pathway of TCP-1 in the kidney was also determined using LC-MS^(n)-*** high specificity and low toxicity of the peptide may be caused by its extremely tight binding to the *** applications for future clinical use,including MRI and PET/CT were also explored,and this research may promote the development of colon cancer diagnostic technology research and provide new ideas and technical routes for tumor diagnostic technology.

关键词： Colon cancer TCP-1 Peptide Cytokeratin 5 Pharmacokinetics/pharmacodynamics(PK/PD)

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Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus

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Journal of Pharmaceutical Analysis 2024年第3期14卷 431-434页

作者： Entezar Berik Zijia Zhang Wei Li Yawen Liu Sihan Chen Wenyong Wu Zhaojun Wang Xinqin Kong Wenqiang Pei Huiqing Dong Huali Long Min Lei Jennifer Yiyang Wang Liangfeng Liu Jinjun Hou Jing Feng Zhaoxia Li Wanying Wu De-an Guo Beijing Key Lab of TCM Collateral Disease Theory Research School of Traditional Chinese MedicineCapital Medical UniversityBeijing100069China National Engineering Research Center of TCM Standardization Technology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of Sciences Beijing100049China School of Chinese materia medica Nanjing University of Chinese MedicineNanjing210029China Limin Pharmaceutical Factory Livzon Group LimitedShaoguanGuangdong512028China Guangdong Corporate Key Laboratory of High-End Liquid Medicine R&D IndustrilizationShaoguanGuangdong512028China Center for Neurological and Psychiatric Research and Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of ScienceShanghai201203China

Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often *** drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine *** hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.

关键词： injection drugs glucocorticoid chemotherapy

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Hypoglycemic activities of flowers of Xanthoceras sorbifolia and identification of anti-oxidant components by off-line UPLC-QTOF-MS/MS-free radical scavenging detection

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Chinese Herbal Medicines 2024年第1期16卷 151-161页

作者： Xiajing Xu Yongli Guo Menglin Chen Ning Li Yi Sun Shumeng Ren Jiao Xiao Dongmei Wang Xiaoqiu Liu Yingni Pan School of Chinese materia medica Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110016China institute of Chinese materia medica China Academy of Chinese Medical SciencesBeijing 100700China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic ***: The AlCl3colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti-oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C18column(2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase(PDB ID: 2CDU) by molecular ***: Combined with the results of activity screening in vitro, the anti-oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatographymass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory ***: The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.

关键词： anti-hyperglycemic activity anti-oxidant flowers of Xanthoceras sorbifolia Bunge NADPH oxidase off-line UPLC-QTOF-MS/MS-free radical scavenging

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Biotransformation and pharmacological activities of platycosides from Platycodon grandiflorum roots

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Chinese Herbal Medicines 2024年第3期16卷 392-400页

作者： Lin Shi Tong Cui Xinyue Wang Rina Wu Junrui Wu Yanqun Wang Weiming Wang College of Food Science Shenyang Agricultural UniversityShenyang 110866China institute of Chinese materia medica Heilongjiang Academy of Chinese Medicine SciencesHarbin 150036China

In Northeast China,Goubao pickle is a popular food fermented from the roots of Platycodon grandiflorum as the main material,offering a unique flavor and rich nutritional *** in roots of *** may play a crucial role in determining the quality of Goubao pickle through microorganism ***,biotransfermation of platycosides has not been reviewed during *** this study,we reviewed platycosides in chemical diversity,metabolic processes in vivo,biotransformation of platycosides in vitro,and pharmacological ***,we also discussed how to improve the bioactive secondary platycosides we desire by regulating enzymes from microorganisms in the future.

关键词： biotransformation Goubao pickle microorganisms pharmacological activities platycosides Platycodon grandiflorum(Jacq.)A.DC

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Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway

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Food Science and Human Wellness 2024年第5期13卷 2703-2717页

作者： Lan Li Shengye Yang Xinyu Liang Yameng Liu Hualing Xu Xiaozhen Guo Cen Xie Xiaojun Xu State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210029China Guangdong Provincial People's Hospital Guangdong Academy of Medical SciencesGuangzhou 510080China School of Chinese materia medica Nanjing University of Chinese MedicineNanjing 210029China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Non-alcoholic fatty liver disease(NAFLD)is the main cause of chronic liver disease *** is widely used in the treatment of non-alcoholic fatty liver,and saikosaponin D(SSD)is one of the main active components of *** purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on“gut-liver axis”.Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice,improved insulin sensitivity,and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase(AST)and alanine aminotransferase(ALT).Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor(Fxr),small heterodimer partner(Shp),recombinant fibroblast growth factor 15(Fgf15)and apical sodium dependent bile acid transporter(Asbt)in the intestine,suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR *** can significantly reduce the gut microbiota associated with bile salt hydrolase(BSH)expression,such as *** BSH expression reduced the ratio of unconjugated to conjugated bile acids,thereby inhibiting the intestinal *** data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acidintestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.

关键词： Saikosaponin D(SSD) Non-alcoholic fatty liver disease Bile acids Gut microbiota Farnesoid X receptor

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Selectively T cell phosphorylation activation of azvudine in the thymus tissue with immune protection effect

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3140-3154页

作者： Ning Sheng Rui Li Yang Li Zhe Wang Lulu Wang Yuhuan Li Jinlan Zhang Jiandong Jiang 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 institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Thymus is the important immune organ,responsible for T cell development and *** lower circulating T counts have been observed in patients who died from COVID-19 compared with ***,also known as FNC,is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 *** this study,single-cell transcriptome,proteomics,and parallel reaction monitoring(PRM)were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey *** results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as *** enzymes involved in the FNC phosphorylation process,such as Dck,Cmpk1,and Nme2,were highly expressed in CD4+ T cells,CD8+ T cells,and DP(CD4+ CD8+)***,FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases,phosphoribosyl transferases,and deaminases,*** robust phosphorylation capacity of the thymus for cytidine analogue drug FNC,and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection *** suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties,as an important factor during antiviral drug design.

关键词： Azvudine T cell Thymus Phosphorylation activation Nucleoside analogue

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Worm-like micelles facilitate the intestinal mucus diffusion and drug accumulation for enhancing colorectal cancer therapy

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Chinese Chemical Letters 2024年第6期35卷 427-432页

作者： Yihan Zhou Duo Gao Yaying Wang Li Liang Qingyu Zhang Wenwen Han Jie Wang Chunliu Zhu Xinxin Zhang Yong Gan State Key Laboratory of Drug Research and Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Chinese materia medica Nanjing University of Chinese MedicineNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China

Local delivery of nanoparticles holds promise for colorectal cancer(CRC)***,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment *** is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal ***,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal *** found that the carriers exhibited diverse shapes while maintaining comparable physicochemical *** these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to ***,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in *** findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.

关键词： Worm-like micelles Mucus penetration Shape dependent Transmucosal delivery Colorectal cancer

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Treatment Options for Hepatocellular Carcinoma Using Immunotherapy: Present and Future

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Journal of Clinical and Translational Hepatology 2024年第4期12卷 389-405页

作者： Hongbin Wei Chunlu Dong Xun Li The First School of Clinical Medicine Lanzhou UniversityLanzhouGansuChina The First Hospital of Lanzhou University LanzhouGansuChina Key Laboratory Biotherapy and Regenerative Medicine of gansu Province LanzhouGansuChina Cancer Prevention and Treatment Center of Lanzhou University School of Medicine LanzhouGansuChina Hepatopancreatobiliary Surgery institute of gansu Province LanzhouGansuChina Clinical Research Center for General Surgery of gansu Province LanzhouGansuChina

Hepatocellular carcinoma(HCC)is a common cancer,and the body’s immune responses greatly affect its progression and the prognosis of *** suppression and the maintenance of self-tolerance in the tumor microenvironment are essential responses,and these form part of the theoretical foundations of *** this review,we first discuss the tumor microenvironment of HCC,describe immunosuppression in HCC,and review the major biomarkers used to track HCC progression and response to *** then examine antibody-based therapies,with a focus on immune checkpoint inhibitors(ICIs),monoclonal antibodies that target key proteins in the immune response(programmed cell death protein 1,anti-cytotoxic T-lymphocyte associated protein 4,and programmed deathligand 1)which have transformed the treatment of HCC and other *** may be used alone or in conjunction with various targeted therapies for patients with advanced HCC who are receiving first-line treatments or subsequent *** also discuss the use of different cellular immunotherapies,including T cell receptor(TCR)T cell therapy and chimeric antigen receptor(CAR)T cell *** then review the use of HCC vaccines,adjuvant immunotherapy,and oncolytic virotherapy,and describe the goals of future research in the development of treatments for HCC.

关键词： Hepatocellular carcinoma Liver cancer Immunotherapy Vaccines

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Pudilan Xiaoyan oral liquid regulates tissue inflammation and apoptosis in mice with influenza virus pneumonia

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Traditional Medicine Research 2024年第6期9卷 55-63页

作者： Shan Cao Shuang-Rong Gao Chen Ni Zi-Han Geng Ying-Li Xu Bo Pang Meng-Ping Chen Yu Zhang Shan-Shan Guo Yu-Jing Shi Li-Qi Ni Kun Wang Rong-Hua Zhao Xiao-Lan Cui Yan-Yan Bao institute of Chinese materia medica China Academy of Chinese Medical SciencesBeijing 100700China Jumpcan Pharmaceutical Group Co. Ltd.Taizhou 225400China

Background:The influenza A virus is the primary cause of respiratory infections and poses a global health *** Xiaoyan oral liquid(PDL)exhibits anti-inflammatory and immunomodulatory *** is commonly employed in clinical practice to manage upper respiratory tract ***,there is still much to uncover regarding its potential therapeutic ***:institute of cancer research mice were infected with influenza A virus via nasal *** general state of the mice,lung index,and lung index inhibition rate were used to evaluate the efficacy of ***-linked immunosorbent assay,western blotting,and immunohistochemistry were used to observe the presence of proteins and cytokines in the lung *** was evaluated using the TUNEL ***:PDL improved the mental state of influenza A virus-infected mice,reduced the lung index,and inhibited viral *** expression of interleukin-1βand tumor necrosis factor-αwere decreased,whereas the expression of interleukin-10 in the lung tissue was increased due to PDL *** addition,PDL treatment modulated Toll-like receptor 4 and MyD88 expressions in the lung *** significantly reduced apoptosis and decreased cleaved caspase-3 and PARP levels,whereas increased B-cell lymphoma-2 expression in the lung ***,the moderate-dose group of PDL exhibited a more pronounced *** findings indicate that PDL exerts a protective effect against pneumonia injury in influenza A virus-infected ***:PDL inhibited the inflammatory response and regulated apoptosis by regulating Toll-like receptor 4 and MyD88 protein expressions,thereby protecting the lung tissue from viral infection-induced lung tissue injury.

关键词： Pudilan Xiaoyan oral liquid influenza A virus immune response apoptosis Toll-like receptors

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