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Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice 认领 引用 被引量：6
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作者 Qiuyan Guo Jiangpeng Wu +14 位作者 Qixin Wang Yuwen Huang Lin Chen Jie Gong Maobo Du Guangqing Cheng Tianming Lu Minghong Zhao Yuan Zhao Chong Qiu Fei Xia Junzhe Zhang Jiayun Chen Feng Qiu Jigang Wang 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2023年第8期908-925,共18页
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,le... Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection. 展开更多
关键词 Tripterygium glycosides tablet Acute liver injury scRNA-seq
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Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis 认领 引用 被引量：8
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作者 Qiuyan Guo Qixin Wang +15 位作者 Jiayun Chen Minghong Zhao Tianming Lu Zuchang Guo Chen Wang Yin Kwan Wong Xueling He Lin Chen Wenjing Zhang Chuanhao Dai Shengnan Shen Huanhuan Pang Fei Xia Chong Qiu Daoyuan Xie Jigang Wang 《Research》 SCIE EI CSCD 2025年第2期627-640,共14页
Rheumatoid arthritis(RA)is an autoimmune disease with features of synovial inflammation,cartilage erosion,bone destruction,and pain and is currently lacking a satisfactory treatment strategy.Dihydroartemisinin(DHA),th... Rheumatoid arthritis(RA)is an autoimmune disease with features of synovial inflammation,cartilage erosion,bone destruction,and pain and is currently lacking a satisfactory treatment strategy.Dihydroartemisinin(DHA),the active metabolite of artemisinin,has exhibited outstanding suppressive effects on RA without obvious side effects.However,the underlying mechanisms remain unclear,which limits its further clinical application.The purpose of this study is to reveal the pharmacodynamic mechanism of DHA against RA by means of a combination of single-cell RNA sequencing(RNA-seq),proteomics,as well as transcriptomics both invivo and invitro.In our results,DHA effectively reduced the degree of redness,swelling,and pain in RA rats and dramatically changed the synovial tissue microenvironment under the pathological state.Within this microenvironment,fibroblasts,macrophages,B cells,and endothelial cells were the major affected cell types,primarily through DHA targeting the extracellular matrix(ECM)structural constituent signaling pathway.In addition,we confirmed that DHA regulated the ECM by modulating matrix metalloproteinase 2(MMP2)and MMP3 in the synovial tissue of RA rats.Moreover,DHA induced apoptosis in MH7A cells,further validating the bioinformatics data.In conclusion,DHA effectively reduced the inflammatory response and improved the immune microenvironment in synovial tissue by inhibiting MMP2 and MMP3.Our findings provide a basis for the application of DHA in the treatment of RA. 展开更多
关键词 reveal pharmacodynamic mechanism proteomics rheumatoid arthritis ra active metabolite dihydroartemisinin single cell RNA sequencing synovial inflammationcartilage rheumatoid arthritis
Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting 认领 引用
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作者 Ruogu Qi Shanshan Wang +8 位作者 Jiayi Yu Tianming Lu Zhiqiang Bi Weibo Liu Yuanyuan Guo Yong Bian Jianliang Shen Xuesong Zhang Wenhao Hu 《Engineering》 SCIE EI CAS CSCD 2024年第5期178-192,共15页
Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations th... Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM. 展开更多
关键词 Multiple myeloma Bortezomib Drug delivery Dual targeting Controlled release
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Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome 认领 引用 被引量：2
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作者 Shuyu Zheng Yanlin Xin +9 位作者 Jiamin Lin Zejuan Xie Keyu Cheng Shanshan Wang Wenli Lu Hao Yang Tianming Lu Jun Li Ruogu Qi Yuanyuan Guo 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2024年第1期152-155,共4页
The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatm... The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2]. 展开更多
关键词 NSCLC eIF4E treatment
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Sequential dual-locking strategy using photoactivated Pt(Ⅳ)-based metallo-nano prodrug for enhanced chemotherapy and photodynamic efficacy by triggering ferroptosis and macrophage polarization 认领 引用 被引量：1
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作者 Jun Li Qiang Zhang +11 位作者 Hao Yang Wenli Lu Yulong Fu Yingcai Xiong Xuan Wang Tianming Lu Yanlin Xin Zejuan Xie Weichao Chen Guoqiang Wang Yuanyuan Guo Ruogu Qi 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2024年第7期3251-3265,共15页
Selective activation of Pt(Ⅳ)prodrugs within tumors has emerged as a promising strategy in tumor treatment.Although progress has been made with photo-and ultrasound-activated Pt(Ⅳ)prodrugs,concerns remain over the n... Selective activation of Pt(Ⅳ)prodrugs within tumors has emerged as a promising strategy in tumor treatment.Although progress has been made with photo-and ultrasound-activated Pt(Ⅳ)prodrugs,concerns remain over the non-specific activation of photosensitizers(PS)and the potential for phototoxicity and chemical toxicity.In this study,a sequential dual-locked Pt(Ⅳ)nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed.The Pt(Ⅳ)prodrug was prepared by conjugating PS-locked Pt(Ⅳ)to a polymeric core,which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug.Under acidic tumor microenvironment conditions,the metallo-nano prodrug undergoes dissociation of iron,triggering a reduction process in oxaliplatin under light irradiation,resulting in the activation of both chemotherapy and photodynamic therapy(PDT).Additionally,the prodrug could induce metallo-triggered ferroptosis and polarization of tumorassociated macrophages(TAM),thereby enhancing tumor inhibition.The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs,making it a promising new direction in cancer treatment. 展开更多
关键词 Dual-locking Pt(Ⅳ)reduction Chemotherapy Photodynamic therapy Ferroptosis Macrophage polarization Medicinal inorganic chemistry Metals in medicine
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