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Active molecule-based theranostic agents for tumor vasculature normalization and.a.titumor efficacy

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Chinese Chemical Letters 2024年第8期35卷 229-234页

作者： Jin Wang Xiaoyan Pan Junyu Zhang Qingqing Zhang Yanchen Li Weiwei Guo Jie Zhang School of Pharmacy Health Science CenterXi’an Jiaotong UniversityXi’an 710061China Center of Ad.a.ced pharmaceuticals and Biomaterials State Key Laboratory of Natural MedicineChina Pharmaceutical UniversityNanjing 210009China

Tumor vascular normalization has emerged.a. a promising strategy for synergistic therapy *** on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QdAU5,which could self-assemble to form functional enzyme infrared QdAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and.a.tigen pre-conditioning and maturation of dendritic cells and Cd8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic ***,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic ***,our findings suggest a prospering strategy to early d.a.nosis and efficient therapy for ovarian cancer without cytotoxicity.

关键词： Tumor vasculature normalization d.a.nosis and treatment Cytotoxicity depleting glutathione Ferroptosis Immune activation

Genomic profiling of colorectal cancer in large-scale Chinese patients:amplification and somatic mutations in ERBB2

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Oncology Research 2024年第9期32卷 1429-1438页

作者： YUZHI LIU EVELYNE BISCHOF ZHIQIN CHEN JIAHUAN ZHOU BEI ZHANG dING ZHANG YONG GAO MING QUAN department of Oncology Shanghai East HospitalTongji University School of MedicineShanghaiChina State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteDepartment of OncologyRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Jiangsu Hengrui pharmaceuticals Co. Ltd.ShanghaiChina d Medicines Inc. ShanghaiChina

Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in cases of HER2 mutant ***:Consequently,further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2(ERBB2)is *** genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes,tumor mutational burden,microsatellite instability,and programmed d.a.h ligand 1(Pd-L1)***:Among 2454 CRC patients,85 cases(3.46%)exhibited ERBB2 amplification,and 55 cases(2.24%)carried ERBB2 mutation.p.R678Q(28%),p.V8421(24%),and p.S310F/Y(12%)were the most prevalent of the 16 detected mutation *** comparison to the ERBB2 altered.a.t)group,KRAS/BRAF mutations were more prevalent in ERBB2 wild-type(wt)samples(ERBB2wt ***2alt,KRAS:50.9%vs.25.6%,pd microsatellite instability high(MSI-H),while no cases with HER2 amplification displayed *** genes varied between ERBB2 copy number variation(CNV)and ERBB2 single nucleotide variant(SNV);TP53 alterations tended to co-occur with ERBB2 amplification(92.3%)as opposed to ERBB2 mutation(58.3%).KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases(KRAS/PIK3CA:45.8%/31.2%)compared to ERBB2 amplification cases(KRAS/PIK3CA:14.1%/7.7%).Conclusion:Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from *** findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.

关键词： Colorectal cancer ERBB2 HER2 Human epidermal growth factor receptor 2 Genetic profiling Precision oncology

Physicochemical characterization of dendrobium officinale polysaccharides and regulation of immunometabolic homeostasis in Sub-health mice based on the Cd4-Th17/Treg immunity axis

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Food Science and Human Wellness 2024年

作者： Bo Li Ze-Hua Zhang Hao-Ru Guan Xing-Li-Shang He Ning Wang Ying-Jie dong Mei Rong Jiu-Jie Jia Ting-Ting Chen Zhi-Yuan Li Gui-Yuan Lv Lin-Nan Zhang Su-Hong Chen Collaborative Innovation Center of Yangtze River delta Region Green pharmaceuticals， Zhejiang University of Technology Zhejiang Provincial Key Laboratory of TCM for Innovative R & d.a.d digital Intelligent Manufacturing of TCM Great Health Products.Huzhou College of Pharmaceutical Science， Zhejiang Chinese Medical University

The aim of this study was to investigate the role of dOPS and dOPS100 in attenuating immune dysfunction in subfertile mice. The results of the study revealed several noteworthy findings. First， dOPS and dOPS100 treatments led to significant improvement in weight gain and reversal of fatigue-related behaviors compared to the normal group. Second， both dOPS and dOPS100 showed effectiveness in reducing immune organ swelling， modulating immunoglobulin （IgA and IgM） levels， and restoring complement （C3c and C4） levels. In addition， they demonstrated.a.significant ability to enhance the integrity of the intestinal mechanical barrier by differentially upregulating the tight junction proteins Occludin and ZO-1. In addition， it was found that dOPS100 specifically enhanced the Cd4+-Th17/Treg immune axis in the gut， as evidenced by increased expression of Foxp3 as well as decreased expression of RORγt， and further modulation of IL-10， IL-22， and IL-17A expression levels of inflammatory factors. These findings collectively suggest that dOPS100 holds significant potential in improving sub-healthy status by repairing the intestinal barrier， restoring local immune homeostasis， and.a.tivating the intestinal immune regulatory network. The study's outcomes provide valuable insights into the therapeutic implications of dOPS and dOPS100 in addressing immune dysfunction in sub-healthy conditions.

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Efficient degradation of aqueous dichloromethane by an enhanced microbial electrolysis cell:degradation kinetics,microbial community and metabolic mechanisms

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Journal of Environmental Sciences 2024年第5期139卷 150-159页

作者： Meng Wu di Zhao Bing Gu ZiruWang Jun Hu Zhiliang Yu Jianming Yu College of Environment College of Biotechnology and BioengineeringCollaborative Innovation Center of Yangtze River Delta Region Green PharmaceuticalsZhejiang University of TechnologyHangzhou 310014China Shentuo Environment(Hangzhou)Co.Ltd. Hangzhou 311121China Zhejiang Tianyi Environmental Co.Ltd. Hangzhou 310000China

dichloromethane(dCM)has been listed.a. a toxic and harmful water pollutant,and its re moval needs *** electrolysis cells(MECs)are viewed.a. a promising alterna tive for pollutant removal,which can be strengthened from two aspects:microbial inocula tion and *** this study,the MEC for dCM degradation was inoculated with the ac tive sludge enhanced by Methylobacterium rhodesianum H13(strain H13)and then acclimated in the form of a microbial fuel cell(MFC).Both the introduction of strain H13 and the initi ation in MFC form significantly promoted dCM *** degradation kinetics were fitted by the Haldane model,with V_(max),K_(h),K_(i)and v_(max)values of 103.2 mg/L/hr,97.8 mg/L268.3 mg/L and 44.7 mg/L/hr/cm^(2),*** cyclic voltammogram implies that dCM redox reactions became easier with the setup of MEC,and the electrochemical impedance spectrogram shows that the acclimated.a.d enriched microbes reduced the charge transfe resistance from the electrode to the *** the biofilm,the dominant genera shifted from Geobacter to Hyphomicrobium in acclimation ***,Methylobacterium played.a. increasingly important *** metabolism mainly occurred through the hydrolytic glutathione S-transferase pathway,given that the gene dcmA was identified rather than the dhlA and P450/*** exogenous electrons facilitated the reduction of GSSG,directly o indirectly accelerating the GSH-catalyzed *** study provides support fo the construction of an efficient and stable MEC for dCM removal in water environment.

关键词： dichloromethane Microbial electrolysis cells Metabolic pathways Electron transfer degradation kinetics

CA IX-targeted.a._(2)S quantum dots bioprobe for NIR-II imaging-guided hypoxia tumor chemo-photothermal therapy

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Journal of Pharmaceutical Analysis 2024年第6期14卷 878-888页

作者： Xinyue Cui Zhuang Hu Ruihan Li Peng Jiang Yongchang Wei Zilin Chen department of Rad.a.ion and Medical Oncology Zhongnan Hospital of Wuhan University and School of Pharmaceutical SciencesWuhan UniversityWuhan430071China Key Laboratory of Combinatorial Biosynthesis and drug discovery Ministry of EducationHubei Province Engineering and Technology Research Center for Fluorinated PharmaceuticalsWuhan430071China

Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the ***,the development of new targeted.a.ents for the accurate d.a.nosis of hypoxia tumors is widely *** carbonic anhyd.a.e IX(CA IX)is abundantly distributed on the hypoxia tumor cells,it is considered.a. a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfonamide(ABS)as a CA IX inhibitor has inherent inhibitory activity and good targeting *** this study,Ag_(2)S quantum dots(Qds)were used.a. the carrier to prepare a novel d.a.nostic and therapeutic bioprobe(Ag_(2)S@polyethylene glycol(PEG)-ABS)through ligand exchange and.a.ide condensation ***_(2)S@PEG-ABS can selectively target tumors by surface-modified.a.S and.a.hieve accurate tumor imaging by the near infrared-II(NIR-II)fluorescence characteristics of Ag_(2)S *** modification of Ag_(2)S Qds greatly improves its water solubility and stability,and therefore achieves high photothermal stability and high photothermal conversion efficiency(PCE)of 45.17%.Under laser irrad.a.ion,Ag_(2)S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in *** also has been proved that Ag_(2)S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good ***,it is a new efficient integrated platform for the d.a.nosis and treatment of hypoxia tumors.

关键词： CA IX-targeted Hypoxia tumor combination therapy NIR-II imaging Photothermal effect

Genus-specific secondary metabolome in Allokutzneria and Kibdelosporangium

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Synthetic and Systems Biotechnology 2024年第3期9卷 381-390页

作者： Man-Jing Ma Wen-Chao Yu Huai-Ying Sun Bing-Cheng dong Gang-Ao Hu Zhen-Yi Zhou Yi Hua Budd.a.Bahadur Basnet Yan-Lei Yu Hong Wang Bin Wei College of Pharmaceutical Science&Collaborative Innovation Center of Yangtze River delta Region Green pharmaceuticals Zhejiang Key Laboratory of GreenLow-Carbonand Efficient Development of Marine Fishery ResourcesZhejiang University of TechnologyHangzhou 310014China Central department of Biotechnology Trihuvan UniversityKathmanduNepal

Rare actinomycete genera are highly recognized.a. a promising source of structurally diverse and bioactive natural *** these genera,Allokutzneria and Kibdelosporangium are two phylogenetically closely related.a.d have been reported to encode some valuable biosynthetic enzymes and secondary ***,there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising *** this study,we first investi-gated the genus-specific secondary metabolic potential in Allokutzneria and Kibdelosporangium by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters(BGCs).The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics *** findings unveiled that the majority(95.4%)of the gene cluster families(GCFs)encoded by Allokutzneria and Kibdelosporangium were genus-specific,including NRPS GCFs encoding *** untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity,with the culture medium having a big impact on the metabolic ***,an MS-cluster featuring a series of hydroxamate-type siderophores was identified from Allokutzneria albata JCM 9917,with two of them,including a novel one(N-deoxy arthrobactin A),being experimentally *** present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.

关键词： Genus-specific secondary metabolism Allokutzneria Kibdelosporangium Genome mining Untargeted metabolomics Siderophore

Phase separation of Nur77 med.a.es XS561-induced.a.optosis by promoting the formation of Nur77/Bcl-2 condensates

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1204-1221页

作者： Xiaohui Chen Meichun Gao Yongzhen Xia Xin Wang Jingbo Qin Hongying He Weirong Liu Xiaowei Zhang Shuangzhou Peng Zhiping Zeng Ying Su Xiaokun Zhang School of Pharmaceutical Science Fujian Provincial Key Laboratory of Innovative Drug Target ResearchXiamen UniversityXiamen 361002China NucMito pharmaceuticals Co. Ltd.Xiamen 361000China department of Clinical Laboratory the Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

The orphan nuclear receptor Nur77 is a critical regulator of the survival and d.a.h of tumor *** pro-d.a.h effect of Nur77 can be regulated by its interaction with Bcl-2,resulting in conversion of Bcl-2 from a survival to *** Bcl-2 is overexpressed in various cancers preventing them from apoptosis and promoting their resistance to chemotherapy,targeting the apoptotic pathway of Nur77/Bcl-2 may lead to new cancer ***,we report our identification of XS561 as a novel Nur77 ligand that induces apoptosis of tumor cells by activating the Nur77/Bcl-2 *** vitro and.a.imal studies revealed.a. apoptotic effect of XS561 in a range of tumor cell lines including MdA-MB-231 triple-negative breast cancer(TNBC)and MCF-7/LCC2 tamoxifen-resistant breast cancer(TAMR)in a Nur77-dependent *** studies showed XS561 potently induced the translocation of Nur77 from the nucleus to mitochondria,resulting in mitochondria-related ***,XS561-induced.a.cumulation of Nur77 at mitochondria was associated with XS561 induction of Nur77 phase separation and the formation of Nur77/Bcl-2 ***,our studies identify XS561 as a new activator of the Nur77/Bcl-2 apoptotic pathway and reveal a role of phase separation in med.a.ing the apoptotic effect of Nur77 at mitochondria.

关键词： XS561 Nur77 Bcl-2 Apoptosis Mitochondria Phase separation TNBC TAMR

Synergy of Prediction Rule and Total Synthesis in Solving the Stereochemical Puzzle of Valactamides

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Precision Chemistry 2024年第3期2卷 120-126页

作者： Tao Zhang Jiaxuan Feng Hid.a.i Oikawa Yian Guo Tao Ye State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate SchoolShenzhen 518055China Innovation Center of Marine Biotechnology and pharmaceuticals School of Biotechnology and Health SciencesWuyi UniversityJiangmen 529020China QianYan(Shenzhen)Pharmatech.Ltd. Shenzhen 518172China

Natural products with diverse functional groups and stereo-genic centers have inspired therapeutics and underpin the modern drug discovery *** three-dimensional molecular structures need to be unambiguously determined in order to be realized.a. clinical candidates or to achieve further activity-guided structural *** recent ad.a.ces in spectroscopic methods have made it possible for researchers to determine the structures of microgram samples of complex natural products,there is no universally accepted method for determining the relative and.a.solute configuration of a naturally occurring *** report the determination of the full stereostructure of valactamide A,an eight-stereogenic-center-containing fungal metabolite by the synergy of prediction rule-guided.a.alysis and chemical *** expedient total synthesis resulted in unambiguous verification of the predicted stereochemistry for valactamide A.

关键词： stereochemistry configuration prediction total synthesis valactamide A

Nitrite-catalyzed economic and sustainable bromocyclization of tryptamines/tryptophols to access hexahydropyrrolo[2,3-b]indoles/tetrahydrofuroindolines in batch and flow

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Chinese Chemical Letters 2024年第7期35卷 247-252页

作者： Xiao Xiao Biao Chen Jia-Wei Li Jun-Bo Zheng Xu Wang Hang Zhao Fen-Er Chen Institute of Pharmaceutical Science and Technology Collaborative Innovation Center of Yangtze River Delta Region Green PharmaceuticalsZhejiang University of TechnologyHangzhou 310014China College of Chemistry and Chemical Engineering Jiangxi Normal UniversityNanchang 330022China Engineering Center of Catalysis and Synthesis for Chiral Molecules Department of ChemistryFudan UniversityShanghai 200433China Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral drugs Shanghai 200433China

A highly efficient and concise bromocyclization has been successfully achieved,in which tryptamine/tryptophol derivates can be transformed to valuable HPI/TFI scaffolds with economic and green ***,a controllable cascade transformation of bromocyclization and.a.omatic bromination has also been smoothly achieved to form dibrominated HPIs and *** could be successfully scaled up under both the batch process and.a.continuous flow *** most remarkable peculiarity of our process over all previous methods is that the generated water is the major ***,successful application of this new protocol has been demonstrated by the pharmaceutical and natural products syntheses.

关键词： Tryptamines and tryptophols Nitrite Economic and sustainable bromocyclization HPI and TFI structures Bath and flow