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Puerarin modulation of CENPA affects downstream PLK1 and CCNB1 expression to inhibit bladder cancer cell proliferation

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Traditional Medicine Research 2024年第9期9卷 32-41页

作者： Hao Xu Wen Gao Deng Pan yu-Yang Ma Ruo-Ran Zhang Yong-Li Cao yu-Chuan Zhou Ming-yu Xu Pei-Yong Zhang kun Pang Department of Urology Xuzhou Central HospitalXuzhou Clinical School of Xuzhou Medical CollegeXuzhou 221009China Graduate School Bengbu Medical UniversityBengbu 233040China Department of Cardiology The Fourth People’s Hospital of JinanJinan 250031China Graduate School Jiangsu UniversityZhenjiang 212013China Department of Urology The Peixian People’s HospitalXuzhou 221699China Department of Clinical Laboratory The First Affiliated Hospital of Harbin Medical UniversityHarbin 150006China

Background:The treatment alternatives for bladder cancer(BLCA),the 10th most prevalent cancer in the world,need to be further investigated,and many active substances like Puerarin in herbal medicine were found to be effective in treating BLCA.The purpose of this study was to investigate the potential treating mechanisms of Puerarin on BLCA.Methods:The cell counting kit 8 assay and flow cytometry were performed to confirm Puerarin’s ability to suppress BLCA.The differentially expressed proteins(DEPs)were obtained by Tandem Mass Tags technology and functional enrichment analysis performed by R studio.The most enriched pathways were selected for study and the DEPs were screened out.Protein-protein interaction network maps were created using String and Cytoscape and key proteins,which will be analyzed for survival,expression,and upstream transcription factor prediction,were screened out using the cytoHubba plugin.CHEA3 was used to obtain upstream transcription factor validated by molecular docking and western blotting experiments.Results:Cell counting kit 8 showed that Puerarin inhibited BLCA cells,with 50%inhibitory concentration of 218μmol/L in T24 and 198μmol/L in 5637.Flow cytometry reveals that Puerarin blocks T24 and 5637 cells in G1 phase.1,385 DEPs were obtained and the enrichment analysis revealed that cell cycle and DNA replication were the two main areas in which DEPs were enriched.Cyclin-B-cyclin dependent kinase 1(CDK1),cyclin B1(CCNB1),and polo-like kinase 1(PLK1)were identified as key proteins,and their upstream transcription factor was predicted to be centromere protein A(CENPA).Puerarin’s binding energy to CENPA was determined by molecular docking to be−6.3 kcal/mol,indicating a strong binding interaction.Western blot showed that Puerarin significantly reduced the expression of CENPA.Conclusion:We hypothesize that Puerarin may inhibit the proliferation of bladder cancer cells by inhibiting CENPA expression to regulate PLK1 and CCNB1 expression,thereby affecting cell cycle.

关键词： Puerarin BLCA Tandem Mass Tags cell cycle

Knocking down AR promotes osteoblasts to recruit prostate cancer cells by altering exosomal circ-DHPS/miR-214-3p/CCL5 pathway

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Asian Journal of Andrology 2024年第2期26卷 195-204页

作者： Zhao Yang Jia-Qi Chen Tian-Jie Liu yu-Le Chen Zhen-kun Ma Yi-Zeng Fan Zi-Xi Wang Shan Xu Ke Wang Xin-Yang Wang Lei Li Hong-Jun Xie Department of Urology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061China

Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis,and the androgen receptor regulates prostate cancer(PCa)progression.It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment,even bone metastases,through exosomes.Here,we found that exosomes isolated from PCa cells after knocking down androgen receptor(AR)or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts.In addition,AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase(circ-DHPS)in PCa cells,which can be transported to osteoblasts by exosomes.Circ-DHPS acts as a competitive endogenous RNA(ceRNA)against endogenous miR-214-3p to promote C-C chemokine ligand 5(CCL5)levels in osteoblasts.Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment.Thus,blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.

关键词： androgen receptor circRNA exosome prostate cancer

Narrowband blue emitter based on fused nitrogen/carbonyl combination with external quantum efficiency approaching 30%

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Science China Chemistry 2024年第1期67卷 351-359页

作者： Long Chen Jia-Heng Cai You-Jun yu Yang-kun Qu Sheng-Yi Yang Sheng-Nan Zou Rui-Hong Liu Dong-Ying Zhou Liang-Sheng Liao Zuo-Quan Jiang Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhou 215123China Macao Institute of Materials Science and Engineering Macao University of Science and TechnologyMacao 999078China

Multi-resonance thermally activated delayed fluorescence(MR-TADF)emitters can enable narrowband emission with high color purity and electroluminescence efficiency.Nitrogen/carbonyl(N/C=O)system is receiving increasing attention while the nitrogen/boron(N/B)system has been widely studied.Donor decoration is an effective approach for N/B type MR-TADF system but always leads to broadening and red-shifting of the emission band in N/C=O MR-TADF system.We attribute these unfavorable phenomena to the formation of intramolecular charge transfer between the MR-core and peripheral donors.To address this issue,we have developed a new strategy by decorating DMQAO(a fused N/C=O MR-core)with a triazine acceptor and a neutral terphenyl group to construct MTDMQAO and MBDMQAO,respectively.The introduction of the triazine acceptor not only realizes efficient narrowband emission in MTDMQAO,but also accelerates the reverse intersystem crossing process through enhanced spin-orbital coupling.As a result,MTDMQAO exhibits a significantly higher external quantum efficiency of 29.4%compared to the referent emitters,validating the rationality of our derivation strategy.This study highlights the potential of the N/C=O system for MR-TADF emitters and provides important insights for understanding the difference between N/B and N/C=O systems.

关键词： carbonyl group narrowband acceptor decoration thermally activated delayed fluorescence OLEDs

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

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Cancer Biology & Medicine 2024年第3期21卷 252-266页

作者： Junya Yan Shibo Wang Jing Zhang Qiangqiang yuan Xianchun Gao Nannan Zhang Yan Pan Haohao Zhang kun Liu Jun yu Linbin Lu Hui Liu Xiaoliang Gao Sheng Zhao Wenyao Zhang Abudurousuli Reyila yu Qi Qiujin Zhang Shundong Cang yuanyuan Lu Yanglin Pan Yan Kong Yongzhan Nie State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Air Force Military Medical UniversityXi'an 710032China Department of Oncology Henan Provincial People's HospitalZhengzhou University People's HospitalZhengzhou 450o03China Faculty of Life Science Northwest UniversityXi'an 710069China Unit 73211 of the People's Liberation Army Nanjing 211800China Key Laboratory of Resource Biology and Biotechnology in Western China(Ministry of Education) School of MedicineNorthwest UniversityXi'an 710069China Shaanxi University of Chinese Medicine Second Clinical Medicine FacultyXi'an 712046China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Renal Cancer and MelanomaPeking University Cancer Hospital and InstituteBeijing 100142China

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

关键词： DNA damage response-related immune activation immune checkpoint inhibitors biomarker gastrointestinal cancer pan-cancer

Supramolecular systems for bioapplications:recent research progress in China

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Science China Chemistry 2024年第5期67卷 1397-1441页

作者： yue-Yang Liu Xiao-Yong yu yu-Chen Pan Hang Yin Shuang Chao yujie Li He Ma Minzan Zuo kun-Xu Teng Jun-Li Hou Yong Chen Dong-Sheng Guo Ruibing Wang yuxin Pei Zhichao Pei Jiang-Fei Xu Xiao-yu Hu Chunju Li Qing-Zheng Yang Leyong Wang yu Liu Zhan-Ting Li State Key Laboratory of Organometallic Chemistry Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional MoleculesShanghai Institute of Organic ChemistryChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200032China Department of Chemistry Fudan UniversityShanghai 200438China College of Chemistry State Key Laboratory of Elemento-Organic ChemistryCollaborative Innovation Center of Chemical Science and EngineeringNankai UniversityTianjin 300071China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China College of Chemistry&Pharmacy Northwest A&F UniversityYangling 712100China Key Lab of Organic Optoelectronics&Molecular Engineering Department of ChemistryTsinghua UniversityBeijing 100084China College of Materials Science and Technology Nanjing University of Aeronautics and AstronauticsNanjing 211106China Key Laboratory of Radiopharmaceuticals Ministry of EducationCollege of ChemistryBeijing Normal UniversityBeijing 100875China Tianjin Key Laboratory of Structure and Performance for Functional Molecules College of ChemistryTianjin Normal UniversityTianjin 300387China State Key Laboratory of Analytical Chemistry for Life Science Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Supramolecular systems feature dynamic,reversible and stimuli-responsive characteristics,which are not easily achieved by molecular entities.The last decade has witnessed tremendous advances in the investigations of supramolecular systems for various bioapplications,which include drug delivery,anticancer therapy,antibacterial therapy,photodynamic therapy,photothermal therapy,combination therapy,antidotes for residual drugs or toxins,and bioimaging and biosensing.Host-guest chemistry has played a key role in the development of such bioactive supramolecular systems,and natural macrocycles(such as cyclodextrins),synthetic macrocycles(such as calixarenes,cucurbit[n]urils,and pillararenes),and porous framework polymers(such as supramolecular organic frameworks and flexible organic frameworks)have been most successfully used as hosts to build different kinds of host-guest systems for attaining designed biofunctions.The self-assembly of rationally designed amphiphilic molecules,macromolecules and polymers represent another important approach for the construction of supramolecular architectures with advanced biofunctions.In this review,we summarize the important contributions made by Chinese researchers in this field,with emphasis on those reported in the past five years.

关键词： host-guest chemistry drug delivery anticancer and antibacterial photodynamic therapy photothermal therapy antidote transmembrane channel bioimaging and biosensing

Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 165-172页

作者： Yan Wang kun Jiang Qiao Xia Xia Kang Shan Wang Ji-Hong yu Wen-Feng Ni Xiao-Qin Qi Ying-Na Zhang Jin-Bao Han Gang Liu Lei Hou Zhi-Chun Feng Liu-Ming Huang Clinical Biobank Center Medical Innovation Research Division of ChinesePLA General HospitalBeijingChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Pediatrics The Seventh Medical Center of PLA General HospitalBeijing 100700China Department of Neurology The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Emergency Center National Center for Children's HealthBeijing Children's HospitalCapital Medical UniversityBeijing 100045China

Background Necrotizing enterocolitis(NEC)is the most common severe gastrointestinal emergency in neonates.We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates.Methods Using the 16S ribosomal DNA(rDNA)sequencing method,we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates:patients undergoing jejunostomy to treat NEC(NP group),neonates undergoing jejunostomy to treat other conditions(NN group),and neonates with NEC undergoing conservative treatment(NC group).We took intestinal feces and saliva samples from patients at different time points.Results The beta diversities of the NP,NN,and NC groups were all similar.When comparing the beta diversities between different time points in the NP group,we found similar beta diversities at time points El to E3 but significant differences between the E2-E3 and E4 time points:the abundances of Klebsiella and Enterococcus(Proteobacteria)were higher at the E1-E3 time points;the abundance of Escherichia-Shigella(Proteobacteria)increased at the E2 time point,and the abundance of Klebsiella decreased significantly,whereas that of Streptococcus increased significantly at the E4 time point.Conclusions Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine.The sources of microbiota in the small intestine of neonates,especially in premature infants,may be affected by multiple factors.

关键词： Microbiota Necrotizing enterocolitis-Small intestine 16S rDNA

Dcalycinumines A-E,Alkaloids with Cytotoxic Activities of Nasopharyngeal Carcinoma Cells from Daphniphyllum calycinum

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Chinese Journal of Chemistry 2024年第1期42卷 35-42页

作者： Qing Tang Xiao-Yong Dai Qiang Lin Zhi-Peng Ling Yi-kun Hao Tian-Xi Zhu Ji-Hui Zhang Yi-Bo Hou Yao-Lan Li Lai-Qiang Huang Jing-Hao Wang Guo-Cai Wang yu-Bo Zhang Guangdong Clinical Translational Centerfor Targeted Drug Department of PharmacologySchoolof MedicineJinan University GuangzhouGuangdong 510632China Institute of Traditional Chinese Medicine&Natural Products Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollegeof PharmacyJinan UniversityGuangzhouGuangdong511443China Institute of Biopharmaceutical and Health Engineering Shenzhen Key Laboratory of Gene and Antibody TherapyState Key Laboratory of Chemical OncogenomicsShenzhen International Graduate SchoolTsinghua UniversityShenzhenGuangdong 518055China The Guangzhou Key Laboratoryof Basic and Translational Research on Chronic Disease Department of PharmacyThe First Affiliated HospitalJinan UniversityGuangzhouGuangdong 510630China

Fivenovel Daphniphyllum alkaloids,named dcalycinumines A-E(1-4,6),andeight previously described Daphniphyllum alkaloids(5,7-13)were isolated from Daphniphyllum calycinum.Compound 1 is the first Daphniphyllum alkaloid possessing a highly rearranged 6/6/6/7/5/6 hexacyclic architecture with a unique 3-methyl-1-azabicyclo[4,4,0]decane ring system.Compound 2 represents a rare diamino Daphniphyllum alkaloid with an unprecedented 6/5/5/6/6/5 carbon skeleton featuring a unique 1-aza-6-azaspiro[4,5]decane unit,whereas 3 also represents a rare diamino Daphniphyllum alkaloid as a possible precursor of 2.Compound 4 is the second example of c-22-nor yuzurimine-type alkaloids.Their structures and absolute configurations were elucidated by HRESIMS,NMR spectroscopic analyses,EcD calculations,and single-crystal X-ray diffraction.Moreover,compound 1 showed remarkable antitumor activities,which could inhibit the proliferation,migration and invasion of nasopharyngeal carcinoma cells,and promoted nasopharyngeal carcinoma cells apoptosis.

关键词： Daphniphyllum calycinum Natural products Daphniphyllum alkaloid Structural elucidation Biological activity Apoptosis Nasopharyngealcarcinoma

A Golden2-like transcription factor, BnGLK1a, improves chloroplast development, photosynthesis, and seed weight in rapeseed

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Journal of Integrative Agriculture 2024年第5期23卷 1481-1493页

作者： Qianwei zhang yuanyi Mao Zikun Zhao Xin Hu Ran Hu Nengwen Yin Xue Sun Fujun Sun Si Chen yuxiang jiang Liezhao Liu kun Lu Jiana Li yu Pan Integrative Science Center of Germplasm Creation in Western China(Chongqing)Science City Southwest UniversityChongqing 400715China Academy of Agricultural Sciences Southwest UniversityChongqing 400715China Engineering Research Center of South Upland Agriculture Ministry of EducationChongqing 400715China Key Laboratory of Horticulture Science for Southern Mountainous Regions Ministry of Education/College of Horticulture and Landscape ArchitectureSouthwest UniversityChongqing 400715China

Enhancing photosynthetic efficiency is a major goal for improving crop yields under agricultural field conditions and is associated with chloroplast biosynthesis and development.In this study,we demonstrate that Golden2-like 1a(BnGLK1a)plays an important role in regulating chloroplast development and photosynthetic efficiency.Overexpressing BnGLK1a resulted in significant increases in chlorophyll content,the number of thylakoid membrane layers and photosynthetic efficiency in Brassica napus,while knocking down BnGLK1a transcript levels through RNA interference(RNAi)had the opposite effects.A yeast two-hybrid screen revealed that BnGLK1a interacts with the abscisic acid receptor PYRABACTIN RESISTANCE 1-LIKE 1-2(BnPYL1-2)and CONSTITUTIVE PHOTOMORPHOGENIC 9 SIGNALOSOME 5A subunit(BnCSN5A),which play essential roles in regulating chloroplast development and photosynthesis.Consistent with this,BnGLK1a-RNAi lines of B.napus display hypersensitivity to the abscisic acid(ABA)response.Importantly,overexpression of BnGLK1a resulted in a 10%increase in thousand-seed weight,whereas seeds from BnGLK1a-RNAi lines were 16%lighter than wild type.We propose that BnGLK1a could be a potential target in breeding for improving rapeseed productivity.Our results not only provide insights into the mechanisms of BnGLK1a function,but also offer a potential approach for improving the productivity of Brassica species.

关键词： Brassica napus BnGLK1a chloroplast development photosynthetic efficiency yield

Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 608-615页

作者： WEI Ya-ru HOU yun-long YIN yu-jie LI Zhen LIU Yi HAN Ning-xin WANG Zi-xuan LIU Lu WANG Xiao-qi HAO yuan-jie MA kun GU Jiao-jiao JIA Zhen-hua Graduate School Hebei University of Chinese Medicine Shijiazhuang Yiling Pharmaceutical New Drug Evaluation Center Hebei Institute of Integrated Traditional and Western Medicine National Key Laboratory for Innovation and Transformation of Luobing Theory Department of Cardiology Hebei Yiling Hospital Graduate School Hebei Medical University

Objective: To investigate the potential role of Tongxinluo(TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI) in mice. Methods: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups(n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril(BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition(EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1(CD31), α-smoth muscle actin(α-SMA), phosphatidylinositol-3-kinase(PI3K) and phospho protein kinase B(p-AKT) were assessed using Western blot. Results: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT(P0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. Conclusion: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

关键词： myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway