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Chinese Chemical Letters 2024年第6期35卷 353-357页

作者： Jinyan Zhang Fen Liu Qian Jin Xueyi Li Qiong Zhan Mu Chen Sisi Wang Zhenlong Wu Wencai Ye Lei Wang state key laboratory of bioactive molecules and druggability assessment Jinan UniversityGuangzhou 510632China Center for bioactive Natural molecules and Innovative Drugs and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchJinan UniversityGuangzhou 510632China College of Pharmacy Jinan UniversityGuangzhou 510632China

The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)*** 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage *** structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical *** pathways for compounds 1-5 were proposed on the basis of the coexisting *** by the biogenetic pathways,the biomimetic synthesis of compound 1 was also ***,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.

关键词： Phloroglucinol-triterpenoid adduct Myrtaceae Building blocks-based molecular network Biomimetic synthesis Antiviral activity Anti-inflammatory activity

Mimotope peptide modified pompon mum-like magnetic microparticles for precise recognition,capture and biotransformation analysis of rituximab in biological fluids

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1317-1328页

作者： Jiawen Yang Aixuan Zhou Minyi Li Qiaoxian He Jingwei Zhou Jacques Crommen Wentao Wang Zhengjin Jiang Qiqin Wang Institute of Pharmaceutical Analysis College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of ChinaJinan UniversityGuangzhou 510632China laboratory for the Analysis of Medicines Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium SCIEX Shanghai 200050China

Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge *** this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first *** from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported *** the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum *** also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient ***,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful ***,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.

关键词： Therapeutic monoclonal antibody Mimotope peptide Precise recognition Peptide-based biomaterials Biotransformation Patient serum

A booming field of large animal model research

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Zoological Research 2024年第2期45卷 311-313页

作者： Xiao-Jiang Li Liangxue Lai Guangdong key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China state key laboratory of bioactive molecules and druggability assessment Jinan UniversityGuangzhouGuangdong 510632China CAS key laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China

Animal models are integral to the study of fundamental biological processes and the etiology of human *** animal models,especially those involving mice,have yielded abundant and significant insights,greatly enhancing ... 详细信息

关键词： mechanisms insight field

Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

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Acta Pharmaceutica Sinica B 2024年第2期14卷 682-697页

作者： Shuran Fan Ming Qi Qi Qi Qun Miao Lijuan Deng Jinghua Pan Shenghui Qiu Jiashuai He Maohua Huang Xiaobo Li Jie Huang Jiapeng Lin Wenyu Lyu Weiqing Deng Yingyin He Xuesong Liu Lvfen Gao Dongmei Zhang Wencai Ye Minfeng Chen state key laboratory of bioactive molecules and druggability assessment Jinan UniversityGuangzhou 510632China Guangdong Province key laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China School of Medicine Jinan UniversityGuangzhou 510632China School of Traditional Chinese Medicine Jinan UniversityGuangzhou 510630China The First Affiliated Hospital of Jinan University Guangzhou 510632China state key laboratory of Chemical Oncogenomics Guangdong Provincial Key Laboratory of Chemical BiologyTsinghua Shenzhen International Graduate SchoolShenzhen 518055China

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer(LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha(FAPα) expression in LNM-CRC cells. Gain-or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis(CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

关键词： Lymphaticmetastasis Colorectal cancer Fibroblastactivation proteinα FAPα-activated prodrug Epithelial-mesenchymal

A comprehensive review on the potential therapeutic benefits of prospective probiotic Christensenella minuta

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Food Science and Human Wellness 2024年

作者： Yueyao Fan Yuhang Xiao Yingying Zhang Shiqing Zhang Weibin Bai Jiali Chen Department of Food Science and Engineering Institute of Food Safety and Nutrition Guangdong Engineering Technology Center of Food Safety Molecular Rapid Detection Jinan University state key laboratory of bioactive molecules and druggability assessment Jinan University Centre for Cancer and Inflammation Research School of Chinese Medicine Hong Kong Baptist University

Bacterial family Christensenellaceae performed high heritability and associated with human health status. Numerous studies observed that the abundance of Christensenellaceae could be significantly reduced in patients with intestinal diseases or metabolic disorders， inferred that it may be treated as an effective biomarker. Christensenella minuta (C. minuta) was the first member of Christensenellaceae family isolated from human fecal samples. Accumulating evidences suggested that C. minuta may demonstrate a positive bio-therapeutic effects toward unhealthy status. Hence， this review aimed to systematically summarize the characterization of Christensenellaceae under specific health or diseases， and discover its promising application. Besides， the latest studies on the pharmacological research of C. minuta also summarized. Current important literatures grasped the potential health benefits of C. minuta in managing metabolic disorders， gut ecosystem， and inflammation. Whereas， several critical knowledge gaps about the safe and clinical application remain should be addressed in future verification. C. minuta is worthy to be elevated as the next prospective probiotic star in nutraceutical or medical field and should not be overlooked.

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GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

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Acta Pharmaceutica Sinica B 2024年第2期14卷 698-711页

作者： Qiwei Jiang Yong Li Songwang Cai Xingyuan Shi Yang Yang Zihao Xing Zhenjie He Shengte Wang Yubin Su Meiwan Chen Zhesheng Chen Zhi Shi Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineState Key Laboratory of Bioactive Molecules and Druggability AssessmentMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Department of Gastrointestinal Surgery&General Surgery the Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Thoracic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China Department of Radiation Oncology The Fifth Hospital of Guangzhou Medical UniversityGuangzhou 510150China state key laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 519000China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA

Glutamate-ammonia ligase(GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

关键词： Gastric cancer GLUL N-Cadherin β-Catenin Enzyme

Multi-omics Approach Reveals Influenza-A Virus Target Genes Associated Genomic, Clinical and Immunological Characteristics in Cancers*

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Biomedical and Environmental Sciences 2024年第7期37卷 698-715页

作者： Jiaojiao Wang Yong Liao Pinglian Yang Weile Ye Yong Liu Chunxia Xiao Weixiong Liao Chunbo Chen Zhiping Liu Zunnan Huang Center of Scientific Research Department of Cardiology Maoming People’s Hospital Maoming 525000 Guangdong China Department of Pharmacy Maoming People’s Hospital Maoming 525000 Guangdong China state key laboratory of bioactive molecules and druggability assessment Jinan University Guangzhou 510632 Guangdong China Guangdong Province key laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of Pharmacy Jinan University Guangzhou 510632 Guangdong China key laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University Key Laboratory of Computer-Aided Drug Design of Dongguan City Key Laboratory for Research and Development of Natural Drugs of Guangdong Province School of Pharmacy Guangdong Medical University Dongguan 523808 Guangdong China Department of Critical Care Medicine Maoming People’s Hospital Maoming 525000 Guangdong China

Objective To examine the precise function of influenza A virus target genes (IATGs) in malignancy. Methods Using multi-omics data from the TCGA and TCPA datasets, 33 tumor types were evaluated for IATGs. IATG expression in cancer cells was analyzed using transcriptome analysis. Copy number variation (CNV) was assessed using GISTICS 2.0. Spearman’s analysis was used to correlate mRNA expression with methylation levels. GSEA was used for the enrichment analysis. Pearson’s correlation analysis was used to examine the association between IATG mRNA expression and IC50. The ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell types. Results In 13 solid tumors, IATG mRNA levels were atypically expressed. Except for UCS, UVM, KICH, PCPG, THCA, CHOL, LAMI, and MESO, most cancers contained somatic IATG mutations. The main types of CNVs in IATGs are heterozygous amplifications and deletions. In most tumors, IATG mRNA expression is adversely associated with methylation. RT-PCR demonstrated that EGFR , ANXA5 , CACNA1C , CD209 , UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines, consistent with the TCGA and GTEx data. Conclusion Genomic changes and clinical characteristics of IATGs were identified, which may offer fresh perspectives linking the influenza A virus to cancer.

关键词： Genomic changes Immune microenvironment Prognosis Drug resistance Experimental validation

Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection

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Biophysics Reports 2024年第1期10卷 15-21页

作者： Qinggang Hao Rui Dong Weiyu Bai Dong Chang Xinyi Yao Yingru Zhang Huangying Xu Huiyan Li Xiang Kui Feng Wang Yan Wang Chengqin Wang Yujie Lei Yan Chen Junling Shen Lei Sang Yan Bai Jianwei Sun Center for Life Sciences Yunnan Key Laboratory of Cell Metabolism and Diseases State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan School of Life Sciences Yunnan University key laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province Yan'an Hospital Affiliated to Kunming Medical University Shandong Provincial key laboratory of Animal Resistance Biology Collaborative Innovation Center of Cell Biology in Universities of Shandong Center for Cell Structure and Function Institute of Biomedical Science College of Life Sciences Shandong Normal University Department of Pathology The Second Affiliated Hospital of Kunming Medical University state key laboratory of bioactive molecules and druggability assessment Institute of Genomic Medicine College of Pharmacy Jinan University Department of Pathology School of Basic Medicine Qingdao University Department of Thoracic Surgery Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

关键词： Melanoma Lung metastasis model Gene screening Tail vein injection

Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

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Acta Pharmaceutica Sinica B 2024年第1期14卷 1-19页

作者： Weile Ye Jiaojiao Wang Peter JLittle Jiami Zou Zhihua Zheng Jing Lu Yanjun Yin Hao Liu Dongmei Zhang Peiqing Liu Suowen Xu Wencai Ye Zhiping Liu International Cooperative laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China Jinan UniversityGuangzhou 510632China Guangdong Province key laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China state key laboratory of bioactive molecules and druggability assessment Jinan UniversityGuangzhou 510632China Pharmacy Australia Centre of Excellence School of PharmacyUniversity of QueenslandWoolloongabba QLD 4102Australia Sunshine Coast Health Institute and School of Health and Behavioural Sciences University of the Sunshine CoastBirtinya QLD 4575Australia National-Local Joint Engineering Lab of druggability and New Drugs Evaluation Guangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Bengbu Medical CollegeBengbu 233030China Institute of Endocrine and Metabolic Diseases the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China

bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of *** biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for *** studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease *** clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia ***,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and *** highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and ***,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

关键词： Cardiovascular disease Atherosclerosis Ginkgo biloba Ginkgolide B Endothelial dysfunction LOX-1 PCSK9 PAF-R antagonist

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胆汁淤积性肝病瘙痒的中西医研究进展

Chinese Medicine and Natural Products 2024年第2期4卷 43-48页

作者：代蚊璋聂红 state key laboratory of bioactive molecules and druggability assessment Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchInternational Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE)College of PharmacyJinan UniversityGuangzhouGuangdongChina

Pruritus is common in cholestatic liver disease,with a high clinical incidence rate and complex *** of potential pruritus inducers such as steroids,bile acids,and lysophosphatidic acid in the systemic circulation is the main cause of pruritus in cholestatic liver ***,clinical treatment of cholestatic liver disease-related pruritus mainly includes medication,intervention therapy,and some experimental ***,there are still problems,such as unclear pathological mechanisms and unsatisfactory treatment responses in some patients with cholestatic liver disease-related *** treatment for patients still faces *** extensively screening patients’plasma(and/or bile)samples through clinical trials,potential pruritus inducers can be identified comprehensively,which can provide a deeper understanding of the itch signaling pathways in cholestatic liver disease and a basis for the development of treatment *** Chinese medicine(TCM)has shown certain characteristics and advantages in clinical *** on the etiology and pathogenesis,external application,internal administration,and TCM-specific therapies have achieved good clinical ***,the combination of Chinese medicine and Western medicine has also achieved more effective treatment for patients with cholestatic liver disease-related *** article will introduce the latest progress in the study of pruritus inducers in cholestatic liver disease and its treatment in TCM and Western medicine.

关键词： cholestasis pruritus Chinese medicine Western medicine research progress