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ADH1C inhibits progression of colorectal cancer through the ADH1C/PHGDH/PS AT1/serine metabolic pathway

中国药理学报（英文版） 2022年第10期43卷 2709-2722页

作者： Sha Li Hong Yang Wan Li Jin-yi Liu Li-wen Ren Yi-hui Yang Bin-bin Ge Yi-zhi Zhang Wei-qi Fu Xiang-jin Zheng Guan-hua Du Jin-Hua Wang The State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050China Key Laboratory of Drug Target Research and Drug Screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China

Colorectal cancer(CRC)is the third most common cancer in men and the second most common cancer in women *** is the second leading cause of cancer-related *** some progress in the treatment of CRC has been achieved,the molecular mechanism of CRC is still *** this study,alcohol dehydrogenase 1C(ADH1C)was first identified as a target gene closely associated with the development of CRC by the comprehensive application of transcriptomics,proteomics,metabonomics and in silico *** ADH1C mRNA and protein expression in CRC cell lines and tumor tissues was lower than that in normal intestinal epithelial cell lines and healthy *** of ADH1C inhibited the growth,migration,invasion and colony formation of CRC cell lines and prevented the growth of xenograft tumors in nude *** inhibitory effects of ADH1C on CRC cells in vitro were exerted by reducing the expression of PHGDH/PSAT1 and the serine *** inhibition could be partially reversed by adding serine to the culture *** results showed that ADH1C is a potential drug target in CRC.

关键词： colorectal cancer ADH1C metabolism PHGDH PSAT1 serine

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Tumorigenic bacteria in colorectal cancer:mechanisms and treatments

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Cancer Biology & Medicine 2022年第2期19卷 147-162页

作者： Sha Li Jinyi Liu Xiangjin Zheng Liwen Ren Yihui Yang Wan Li Weiqi Fu Jinhua Wang Guanhua Du The State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050China Key Laboratory of Drug Target Research and Drug Screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China

Colorectal cancer(CRC)is the third most common and the second most fatal *** recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of *** bacterial species,such as Fusobacterium nucleatum,Escherichia coli,Bacteroides fragilis,Enterococcus faecalis,and Salmonella *** been associated with CRC,based upon sequencing studies in CRC patients and functional studies in cell culture and animal *** bacteria can cause host DNA damage by genotoxic substances,including colibactin secreted by pks+Escherichia coli,*** toxin(BFT)produced by Bacteroides fragilis,and typhoid toxin(TT)from *** bacteria can also indirectly promote CRC by influencing host-signaling pathways,such as E-cadherin/β-catenin,TLR4/MYD88/NF-κB,and SMO/RAS/p38 ***,some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function,creating a proinflammatory environment,or influencing the autophagy *** with the classical antibacterial drugs,metronidazole or erythromycin,the antibacterial active ingredients,M13@Ag(electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13),berberine,and zerumbone,were found to inhibit tumorigenic bacteria to different *** this review,we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria,as well as progress in developing effective antibacterial *** bacteria have been shown to be active in the oncogenesis and progression of CRC,and some antibacterial compounds have shown therapeutic potential in bacteria-induced *** bacteria may be useful as biomarkers or therapeutic targets for CRC.

关键词： Colorectal cancer microbiota tumorigenic mechanism genotoxicity cancer pathways tumor immunity

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Identification of anti-Mycobacterium tuberculosis agents targeting the interaction of bacterial division proteins FtsZ and SepFe

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2056-2070页

作者： Hongjuan Zhang Ying Chen Yu Zhang Luyao Qiao Xiangyin Chi Yanxing Han Yuan Lin Shuyi Si 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

Tuberculosis(TB)is one of the deadly diseases caused by Mycobacterium tuberculosis(Mtb),which presents a significant public health *** of TB relies on the combination of several anti-TB drugs to create shorter and safer ***,new anti-TB agents working by different mechanisms are urgently ***,a tubulin-like protein with GTPase activity,forms a dynamic Z-ring in cell *** of FtsZ inhibitors are designed to inhibit GTPase *** Mtb,the function of Z-ring is modulated by SepF,a FtsZ binding *** FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of ***,we established a yeast twohybrid based screening system to identify inhibitors of FtsZ/SepF interaction in *** this system,we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and ***,we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down,fluorescence polarization(FP),surface plasmon resonance(SPR)and CRISPRi knockdown ***,T0349 can inhibit bacterial cell division by inducing filamentation and abnormal *** data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

关键词： Anti-Mycobacterium tuberculosis FtsZ SepF Bacterial division Yeast two-hybrid CRISPRi Protein—protein interaction Inhibitor

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Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis

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Journal of Pharmaceutical Analysis 2024年第8期14卷 1140-1157页

作者： Weilun Cheng Wanqi Mi Shiyuan Wang Xinran Wang Hui Jiang Jing Chen Kaiyue Yang Wenqi Jiang Jun Ye Baoliang Guo Yunpeng Zhang Department of General Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbin150001China College of Bioinformatics Science and Technology Harbin Medical UniversityHarbin150081China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China

Breast cancer remains a leading cause of mortality in women ***-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic *** the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable *** the scope of our study,high heterogeneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue ***,TNBC exhibited significant specificity regarding cell proliferation,differentiation,and disease *** associations between tumor grade,prognosis,and TNBC oncogenes were established via pseudotime trajectory ***,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in ***,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor *** genes in these three cluster cells could therefore serve as potential therapeutic targets for *** collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as *** further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse ***,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

关键词： Triple-negative breast cancer Single-cell RNA sequencing Epithelial-mesenchymal transition Macrophage polarization Therapeutic drugs Bioinformatics

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A new look at herbal extracts

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Science China(Life Sciences) 2023年第10期66卷 2441-2442页

作者： 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 CollegeBeijing100050China

Traditional Chinese Medicine(TCM)has been used to treat a wide variety of diseases in China for thousands of *** clinical efficacy and safety of TCM targeting different diseases have been recorded and observed(Chinese Pharmacopoeia Commission,2020).In the past centuries,hundreds of effective medicinal components of TCM have been extracted and isolated.

关键词： herbal diseases Medicine

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Research advances of nanoparticles for CAR-T therapy in solid tumors

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Chinese Chemical Letters 2024年第9期35卷 72-82页

作者： Bohan Chen Liming Gong Jing Feng Mingji Jin Liqing Chen Zhonggao Gao Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China School of Pharmacy Qingdao UniversityQingdao 266071China

As one of the most promising adoptive T-cell therapies,chimeric antigen receptor T-cell(CAR-T)therapy has acquired Food and Drug Administration(FDA)approval for a variety of products and has been used successfully in the treatment of malignant hematological ***-T therapy,on the other hand,faces a number of obstacles in the field of solid tumor therapy that limit its widespread clinical *** advances in nanoparticle research in cancer therapy and immunotherapy have been made in recent years,providing novel strategies to address the challenges encountered by CAR-T therapy in the treatment of solid *** review commences with a comprehensive explanation of the basic framework of CAR-T therapy as well as the challenges it faces in the treatment of solid ***,we encapsulate a summary of the developmental research combining nanoparticles with CAR-T cells for the treatment of solid tumors,which includes gene transfection,cell activation and expansion,targeted infiltration,immune escape inhibition,and combination with other *** with the overview of the research progress,a discussion has been initiated on the challenges and perspectives of CAR-T based on nanoparticles.

关键词： CAR-T therapy Nanoparticles Solid tumors Immunotherapy T cell

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Tumor-responsive covalent organic polymeric nanoparticles enhancing STING activation for cancer immunotherapy

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Chinese Chemical Letters 2025年第3期36卷 357-362页

作者： Shuang Liang Jianjun Yao Dan Liu Mengli Zhou Yong Cui Zhaohui Wang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China School of Life Sciences and Biopharmaceutical Science Shenyang Pharmaceutical UniversityShenyang 110016China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

The cyclic guanosine monophosphate-adenosine monophosphate synthase and the stimulator of interferon genes(cGAS-STING)has emerged as a promising target for cancer ***,the development of natural STING agonists is impeded by several challenges,including limited biostability,poor pharmacokinetics,and inefficient cytosolic ***,we meticulously designed a doublelayer polyethylenimine(PEI)modified nanoscale covalent organic polymer(CPGP)for efficient delivery of 23cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),a natural STING *** double-layer PEI structured CPGP enhanced both the loading capacity and stability of ***,CPGP improved the intracellular delivery efficiency and amplified the activation of STING pathway for the secretion of type-I interferon and pro-inflammatory *** contrast,single-layered nanoparticles failed to permit stable loading and intracellular delivery of cGAMP for immune *** nano-STING agonist also mitigated the immunosuppressive tumor microenvironment(TME)by reducing regulatory T cells and polarizing M2 macrophages to the M1 phenotype,thereby creating an immune-supportive TME to enhance adaptive immune *** combination of CPGP and immune checkpoint blockers showed synergistic effect,further enhancing the inhibition effect on tumor *** double-layer PEI modified CPGP may offer a generalizable platform for other natural dinucleotide STING agonists to overcome the cascade delivery barriers,augmenting immune activation for tumor immunotherapy.

关键词： Immunotherapy Covalent organic polymers Delivery STING agonists Nanoparticle

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A comprehensive review of meal replacement from dining table to sickbed:beyond biomedical potentials

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Food Science and Human Wellness 2025年第3期14卷 822-834页

作者： Hao Qiang Tianshu Xu Peng Ma Siyuan Zhang Guanhua Du Guifen Qiang Tengfei Ji State Key Laboratory of Bioactive Substance and Function of Natural Medicines Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China School of Chemistry Cardiff UniversityCardiff CF103XQUK Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

The emergence of meal replacement(MR)originates from physical exercise or fitness as a substitute for one or all meals and later expands to the field of weight ***,the main application of current meal replacement is to lose body weight,whether patients with obesity,diabetes,fatty liver,infertile or pregnant women can benefit from weight *** addition,MRs still exhibit more biomedical potential in preventing and treating diseases,like anti-diabetes,improving fatty liver and kidney disease,preventing cancer,conceiving and reducing pregnancy complications,and improving life ***,there are also disadvantages to meal replacement,including causing adverse effects,although most are acceptable and *** date,various commercially-developed MRs are walking from dining table to ***,a scientific understanding of the advantages and disadvantages of meal replacements is crucial for their extensive application beyond biomedical potentials.

关键词： Meal replacement Weight loss Biomedical potentials

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Development and validation of a UPLC-HR-SIM method to quantify semaglutide for its pharmacokinetic study

Intelligent Pharmacy

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Intelligent Pharmacy 2025年第2期3卷 143-149页

作者： Xinyi, Jiang Tong, Li Meng, Yu Yiran, Zhao Xiangyi, Wang Yanhe, Zhou Xinmiao, Guo Jiuming, He Jianpeng, Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China Shanxi Mengtaiberg Biotechnology Co. Ltd. ShanXi China NMPA Key Laboratory for Safety Research and Evaluation of Innovative Drug Beijing China

Aim: To develop a highly sensitive and interference-resistant ultra performance liquid chromatography (UPLC) coupled with high-resolution selected ion monitoring (HR-SIM) mass spectrometry method for the quantification of semaglutide in biological samples, and to apply it for pharmacokinetic analysis. Method: The UPLC-HR-SIM method was utilized to quantify semaglutide in beagle plasma, requiring minimal sample pretreatment. The method demonstrated a lower limit of quantification (LLOQ) of 5.0 ng/mL for semaglutide in beagle plasma. Results: Following intravenous (iv) administration at a dose of 0.030 mg/kg, the plasma concentration of semaglutide in beagles exhibited a multi-exponential decay pattern, with an average elimination half-life (t_1/2) of 44.90 ± 11.45 h. Conclusions: The UPLC-HR-SIM method has proven to be a highly sensitive and robust approach for the quantification of peptide-based drugs. This method will enhance the understanding of the pharmacokinetics and pharmacodynamics of semaglutide and facilitate further research into the pharmacokinetics of other peptide therapeutics. © 2025 The Authors

关键词： HR-SIM LC-MS Pharmacokinetics Quantification Semaglutide

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Correction: MELK is an oncogenic kinase essential for metastasis, mitotic progression, and programmed death in lung carcinoma

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3533-3536页

作者： Qin Tang Wan Li Xiangjin Zheng Liwen Ren Jinyi Liu Sha Li Jinhua Wang Guanhua Du The State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing China Key Laboratory of Drug Target Research and Drug Screen Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College 100050 Beijing China

After online publication of the article[1]the authors noticed inadvertent errors in the panel of 95-D cells(+MELK and-siSlug)invasion in Fig.2J which is partly overlapped with the panel of the 95-D cells(+MELK and+siS... 详细信息

关键词： MMP7 metastasis death

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