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Precise nano-system-based drug delivery and synergistic therapy against androgen receptor-positive triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2685-2697页

作者： Fangyan Gao Yueyao Wu Runtian Wang Yuhui Yao Yiqiu Liu Lingling Fan Jingtong Xu Jian Zhang Xin Han Xiaoxiang Guan Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Collaborative innovation center of Chinese Medicinal Resources Industrialization School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Department of Oncology the Second Hospital of NanjingNanjing University of Chinese MedicineNanjing 210023China Department of Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Targeting androgen receptor(AR)has shown great therapeutic potential in triple-negative breast cancer(TNBC),yet its efficacy remains ***,we aimed to identify promising targeted agents that synergize with enzalutamide,a second-generation AR inhibitor,in *** using a strategy for screening drug combinations based on the Sensitivity Index(SI),we found that MK-8776,a selective checkpoint kinase1(CHK1)inhibitor,showed favorable synergism with enzalutamide in AR-positive *** combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776,***,a nanoparticle-based on hyaluronic acid(HA)-modified hollow-manganese dioxide(HMnO_(2)),named HMnE&M@H,was established to encapsulate and deliver enzalutamide and *** HA-modified nanosystem managed targeted activation via pH/glutathione ***&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a ***,our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H,providing a potential therapeutic approach for the treatment of TNBC.

关键词： Triple-negative breast cancer Androgen receptor Checkpoint kinase 1 Enzalutamide MK-8776 Synergy HMnO_(2) Nanodrug delivery system

Babao Dan Inhibits Gastric Cancer Progression in vivo Through Multiple Signaling Pathways

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World Journal of Traditional Chinese medicine 2024年第1期10卷 14-21页

作者： Hai-Xia Shang Yi Fang Bin Guan Jian-Hua Guan Jun Peng Jin-Yan Zhao Jiu-Mao Lin Institute of Oncology of Academy of integrative medicine Fujian University of Traditional Chinese MedicineFuzhouFujianChina Key Laboratory of integrative medicine of Fujian Province University Fujian University of Traditional Chinese MedicineFuzhouFujianChina Fujian Key Laboratory of integrative medicine on Geriatric Fujian University of Traditional Chinese MedicineFuzhouFujianChina innovation and Transformation center Fujian University of Traditional Chinese MedicineFuzhouFujianChina Xiamen Traditional Chinese medicine Co. Ltd.XiamenFujianChina

Objective:The aim of this study was to explore the effects of Babao dan(BBD),a traditional Chinese medicine,on gastric cancer(GC)progression in *** and Methods:A subcutaneous xenograft mouse model of GC was established using MGC80-3 *** terminal deoxynucleotidyl transferase-mediated dUTP:2'-deoxyuridine 5'-triphosphate-biotin nick-end labeling method was adopted to detect cell apoptosis in *** expression levels of proteins associated with proliferation,apoptosis,and angiogenesis were measured by immunohistochemical staining or western blotting(WB).The activation and protein levels of p-c-Jun N-terminal kinase(JNK),p-p38,p-extracellular-regulated kinase 1/2,p-nuclear factor-κB(NF-κB),and p-STAT3 were examined by Bio-plex and ***:BBD significantly inhibited tumor growth in GC mouse models with no adverse effect on body weight or organ *** was also found that BBD significantly suppressed the proliferation of GC tumor cells,induced the apoptosis of tumor cells,and inhibited angiogenesis through inactivating with mitogen-activated protein kinase,NF-κB,and STAT3 ***:BBD exerts suppressive effects on GC tumor growth by regulating multiple pathways in vivo,which may provide a novel treatment option for GC therapy.

关键词： Babao dan gastric cancer multiple signaling pathways proliferation traditional Chinese medicine

integrative transcriptome analysis identifies MYBL2 as a poor prognosis marker for osteosarcoma and a pan-cancer marker of immune infiltration

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Genes & Diseases 2024年第3期11卷 351-367页

作者： Xinzhu Quiu Hongbo He Hao Zeng Xiaopeng Tongg Can Zhang Yupeng Liu Zhan Liao Qing Liu Department of Orthopaedics Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical Research center for Geriatric Disorders Xiangya HospitalChangshaHunan 410008China Department of sports medicine Research Center of Sports MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China

MYBL2(MYB proto-oncogene like 2)is an emerging prognostic marker for malignant tumors,and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be *** constructed a transcription factor activity profile of os-teosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression ***,we calcu-lated the extent of MYBL2 activation in malignant proliferative *** also explored the association between MYBL2 and chemotherapy resistance in ***,we systematically correlated MYBL2 with immunological signatures in the tumor microenviron-ment in pan-cancer,including immune cell infiltration,immune checkpoints,and tumor immu-notherapy ***,we developed and validated a risk score(MRGS),derived an osteosarcoma risk score nomogram based on MRGS,and tested its ability to predict ***2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune ***2 expres-sion positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell ***-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived sup-pressor cells,Th2 cell infiltration,CD276,RELT gene expression,and tumor mutation burden.

关键词： Biomarker Immunecheckpoint MYBL2 Osteosarcoma Pan-cancer

Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

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Chinese Journal of integrative medicine 2024年第6期30卷 515-524页

作者： CAO Liu-jing LIU Li-ya CHEN You-qin HAN Yu-ying WEI Li-hui YAO Meng-ying FANG Yi WU Mei-zhu CHENG Ying Thomas J.Sferra LIU Hui-xin LI Li PENG Jun SHEN A-ling Clinical Research Institute the Second Affiliated Hospital&Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhou350122China Fujian Key Laboratory of integrative medicine in Geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Pediatrics Case Western Reserve University School of MedicineUH Rainbow Babies and Children’s HospitalClevelandOH44106USA innovation and Transformation center Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Health Management Fujian Provincial HospitalShengli Clinical College of Fujian Medical UniversityFuzhou000000China

ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) *** polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in *** treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

关键词： colorectal cancer Pien Tze Huang Chinese medicine partner of NOB1 proliferation p53/p21 pathway

高吸附电化学纤维传感器用于实时、准确检测颅内一氧化氮

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Science China Materials 2024年第4期67卷 1320-1331页

作者：高睿王列李丹宋杰栗乾明卢江李录河李亦冉叶婷婷王嘉诚焦一丁李方琰何儿任俊烨张晔 National Laboratory of Solid State Microstructures Jiangsu Key Laboratory of Artificial Functional MaterialsChemistry and Biomedicine Innovation CenterCollaborative Innovation Center of Advanced MicrostructuresCollege of Engineering and Applied SciencesNanjing UniversityNanjing 210023China Department of Immunology School of Medicine and Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China

电化学一氧化氮传感器能够实时监测颅内一氧化氮浓度,对于了解大脑中一氧化氮的功能至关重要.然而,在大脑中使用的传统刚性传感电极面临着灵敏度低和植入后神经炎症引起一氧化氮浓度异常的问题.在这里,我们报道了一种结合物理和化学吸... 详细信息

电化学一氧化氮传感器能够实时监测颅内一氧化氮浓度,对于了解大脑中一氧化氮的功能至关重要.然而,在大脑中使用的传统刚性传感电极面临着灵敏度低和植入后神经炎症引起一氧化氮浓度异常的问题.在这里,我们报道了一种结合物理和化学吸附能力、具有高灵敏度和准确性的电化学一氧化氮传感器.其对一氧化氮的物理和化学吸附能力分别来自于电极的高比表面积和丰富的羧基官能团.此外,柔软的电极可以与脑组织的力学性能相匹配,实现了一个高度适应的电极/组织界面.由此设计的颅内一氧化氮传感器表现出迄今为止所报道文献中最高的灵敏度,为3245 pA nmol^(-1)L,检测限为0.1 nmol L^(-1).电极在植入后未观察到显著的炎症反应以及过量的一氧化氮表达,提高了检测的准确性.该传感器成功捕捉了大脑中的一氧化氮波动,并实现了对多个脑区的同时检测,促进了对大脑中一氧化氮生理病理作用的研究.

关键词：一氧化氮浓度生理病理传感电极化学纤维组织界面电化学

Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Nano Research 2024年第4期17卷 2949-2959页

作者： Lin Yang Xueying An Wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang Division of sports medicine and Adult Reconstructive Surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospital Clinical College of Nanjing Medical University321 Zhongshan RoadNanjing 210008China Branch of National Clinical Research center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China State Key Laboratory of Pharmaceutical Biotechnology Medical SchoolNanjing University&Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal ***,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption ***,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption ***,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast ***,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt *** conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关键词： osteoporosis α-cyperone osteoclast phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome

Toosendanin: upgrade of an old agent in cancer treatment

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Chinese Journal of Natural medicines 2024年第10期22卷 887-899页

作者： LI Shuwei XIONG Qingyi SHEN Yiwen LIN Jiayi ZHANG Lijun WU Ye JIN Jinmei LUAN Xin Shanghai Frontiers Science center for Chinese medicine Chemical Biology Institute of Interdisciplinary integrative medicine Research and Shuguang Hospital Shanghai University of Traditional Chinese medicine

Toosendanin(TSN), a tetracyclic triterpenoid derived from Melia toosendan and M. azedarach, demonstrates broad application prospects in cancer treatment. Although previously employed as a pesticide, recent studies have revealed its potential therapeutic value in treating various types of cancer. TSN exerts an anticancer effect via mechanisms including proliferation inhibition, apoptosis induction, migration suppression, and angiogenesis inhibition. However, TSN's toxicity, particularly its hepatotoxicity, significantly limits its therapeutic application. This review explored the dual nature of TSN, evaluating both its anticancer potential and toxicological risks, emphasizing the importance of balancing these aspects in therapeutic applications. Furthermore, we investigated the incorporation of TSN into novel therapeutic strategies, such as Proteolysis-targeting chimeras(PROTAC) technology and nanotechnology-based drug delivery systems(DDS), which enhance treatment efficacy while mitigating toxicity in normal tissues.

关键词： Cancer therapy Hepatotoxicity Nano-delivery systems PROTAC Toosendanin

Oral pyroptosis nanoinhibitor for the treatment of inflammatory bowel disease

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Nano Research 2024年第3期17卷 1748-1759页

作者： Zhenxing Zhu Dongtao Zhou Yi Yin Zhun Li Zhen Guo Yongchun Pan Yanfeng Gao Jingjing Yang Weiming Zhu Yujun Song Yi Li Department of General Surgery Affiliated Jinling HospitalMedical SchoolNanjing UniversityNanjing 210093China College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China Department of General Surgery Affiliated Drum Tower HospitalMedical SchoolNanjing UniversityNanjing 210008China Department of Biochemistry and Molecular Biology School of Medicine&Holistic Integrative MedicineJiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

Inflammatory bowel disease(IBD)is an autoimmune gastrointestinal disease characterized by chronic relapsing inflammation of the *** pyroptosis that exists in the inflamed intestine can activate damage signals and aggravate local inflammation in ***,we designed an oral pyroptosis nanoinhibitor,DXMS@CuM@PPADT@PSS(DCMP),which can target intestinal lesions,and respond to reactive oxygen species(ROS)to release active sites and drugs at the *** can inhibit the activation of the nucleotide-binding domain and leucine-rich repeat family pyrin domain containing 3(NLRP3)inflammasomes by scavenging ROS,resulting in the down-regulation of gasdermin D(GSDMD)cleavage thus inhibiting *** also improved intestinal barrier function,decreased inflammatory cytokine levels,and increased the diversity of gut microbiota in mice with *** work is believed to expand the biomedical application of nanomaterials for innate immunity modulation.

关键词： inflammatory bowel disease nanoinhibitors pyroptosis synergistic therapy antioxidant

Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment

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Chinese Journal of Natural medicines 2024年第6期22卷 501-514页

作者： CHEN Chiwei HUANG Renlun WANG Neng ZHENG Yifeng ZHOU Jianfu YANG Bowen WANG Xuan ZHANG Juping PAN Bo CHEN Zhiqiang WANG Shengqi WANG Zhiyu XIANG Songtao The Research center of integrative Cancer medicine Discipline of Integrated Chinese and Western Medicinethe Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510000China The First Clinical College of Guangzhou University of Chinese medicine Guangzhou 510000China Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese medicine Syndrome Guangdong Provincial Academy of Chinese Medical SciencesGuangdong Provincial Hospital of Chinese MedicineGuangzhou 510000China Guangdong-Hong Kong-Macao Joint Lab on Chinese medicine and Immune Disease Research Guangzhou University of Chinese MedicineGuangzhou 510000China The Research center for integrative medicine School of Basic Medical SciencesGuangzhou University of Chinese MedicineGuangzhou 510000China State Key Laboratory of Dampness Syndrome of Chinese medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000China

Prostate cancer(PCa)is the second most common malignancy among men *** Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of *** study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 *** conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their *** showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM ***,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by *** FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity *** studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture ***,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 ***,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

关键词： Traditional Chinese medicine Tumor-associated macrophages Prostate cancer stem cells CCL5 Tumor microenvironment