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Curcumin modulates oxidative stress to inhibit pyroptosis and improve the inflammatory microenvironment to treat endometriosis

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Genes & Diseases 2024年第3期11卷 102-105页

作者： Jie Ding Shanshan Mei Kaili Wang Wen Cheng Shuai Sun Zhexin Ni Xiaoqiu Wang Chaoqin Yu department of Gynecology of Traditional Chinese Medicine Changhai Hospital Affiliated to Naval Medical UniversityShanghai 200433China Obstetrics and Gynecology department The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouZhejiang 310006China department of pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Obstetrics and Gynecology Hospital of Fudan University Shanghai 200433China

Endometriosis(EM)is a common disease that affects approximately 10%-15%of women of childbearing age.The pathogenesis of EM is unclear,but studies have shown a strong association between EM and inflammation,as well as oxidative stress.^(1) Pyroptosis is also called inflammatory cell death.When pyroptosis occurs,it activates a strong inflammatory response.Pyroptosis is associated with oxidative stress,and Ros act as intermediate triggers to activate pyroptosi.

关键词： inflammatory death oxidative

Synthetic host-guest pairs as novel bioorthogonal tools for pre-targeting

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Chinese Chemical Letters 2024年第2期35卷 44-56页

作者： Yan-Long Ma Shi Yan Xiong-Jie Xu Hua Cao Ruibing Wang School of Chemistry and Chemical Engineering and Guangdong Cosmetics Engineering & technology Research Center Guangdong Pharmaceutical UniversityZhongshan 528458China State Key Laboratory of Quality Research in Chinese Medicine and the Institute of Chinese Medical ScienceUniversity of MacaoMacao 999078China

Due to its simplicity, high efficiency, and chemo-selectivity, bioorthogonal chemistry has shown a great application potential in pre-targeting.Currently, four bioorthogonal pairs as targeting tools, including (strept)avidin/biotin, antibody/antigen, oligonucleotide hybridization and IEDDA tools, have been developed and applied in targeted delivery.Nevertheless, all of these tools still suffer from some limitations, such as difficult modification, biochemical fragility and larger molecular weight for biological association tools, as well as chemical instability for IEDDA tools.Synthetic host-guest pairs with relatively small molecular sizes not only possess strong chemical stability, but also have the features of fast conjugation rate, tunable binding affinity , easy modification, and high chemo-selectivity.Consequently, they can be used as a novel non-covalent bioorthogonal tool for pre-targeting.In order to further promote the development of host-guest pairs as novel bioorthogonal tools for pre-targeted delivery, we firstly calculate their conversion rate to make researcher aware of their unique advantages;next, we summarize the recent research progress in this area.The future perspectives and limitations of these unique tools will be discussed.This review will provide a systemic overview of the development of synthetic host-guest pairs as novel bioorthogonal tools for pre-targeting, and may serve as a “go for” resort for researchers who are interested in searching for new synthetic tools to improve pre-targeting.

关键词： Bioorthogonal chemistry Synthetic host-guest pairs Pre-targeting Molecular recognition Biomedical applications

Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 51-64页

作者： Mingming XU Zhaoliang LIU Wenhua HU Ying HAN Zhen WU Sufeng CHEN Peng XIA Jing DU Xumin ZHANG Piliang HAO Jun XIA Shuang YANG Center for Clinical Mass Spectrometry College of Pharmaceutical SciencesSoochow UniversitySuzhou215123China School of Life Science and technology ShanghaiTech UniversityShanghai201210China State Key Laboratory of Genetic Engineering Department of BiochemistrySchool of Life SciencesFudan UniversityShanghai200438China department of Clinical Laboratory Center Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou310014China

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

关键词： Pancreatic cancer Glycosylation Biomarker Glycoproteomics Mass spectrometry

Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

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Asian Journal of pharmaceutical Sciences 2024年第1期19卷 18-34页

作者： Yuankai Sun Xinchi Jiang Jianqing Gao Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang UniversityHangzhou 310058China department of Pharmacy The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

关键词： Ischemic stroke Stem cell therapy Stem cell modification Cell therapy challenge

Visible light cross-linking and bioactive peptides loaded integrated hydrogel with sequential release to accelerate wound healing complicated by bacterial infection

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Nano Research 2024年第3期17卷 1737-1747页

作者： Guiyan Wang Ning Yuan Jun Zhang Man Qin Suwei Dong Yuguang Wang department of Pediatric Dentistry Peking University School and Hospital of StomatologyBeijing 100081China State Key Laboratory of Natural and Biomimetic Drugs Chemical Biology Centerand School of Pharmaceutical SciencesPeking UniversityBeijing 100191China department of Prosthodontics Peking University School and Hospital of StomatologyBeijing 100081China

The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge.The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds.Here,a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed.The antibacterial peptide that consists of 11 residues(CM11,WKLFKKILKVL)is loaded onto acrylate-modified gelatin through charge interactions.A vascular endothelial growth factor mimetic peptide KLT(KLTWQELYQLKYKGI)with a GCG(Gly-Cys-Gly)modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction.In this reaction,the acrylate gelatin undergoes cross-linkage within seconds.Based on the physical/chemical double crosslinking strategy,the bioactive peptides achieve sustained and sequential release.The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus(MRSA)growth through the rapid release of CM11 peptides at early stage;it forms obvious growth inhibition zones against pathogenic bacterial strains.Moreover,cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides.In a mouse skin wound infected with self-luminous MRSA,the CM11/KLT-functionalized hydrogels enhance wound healing,with rapidly bacterial infection reduction,lower expression of inflammatory factors,and neovascularization promotion.These results suggest that the rationally designed,sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.

关键词： antimicrobial peptide vascular endothelial growth factor(VEGF)mimetic peptide sequential release visible-light crosslinking hydrogel wound therapy

The marriage of immunomodulatory,angiogenic,and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scafold for military medicine

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Military Medical Research 2024年第3期11卷 323-344页

作者： Ping Wu Lin Shen Hui-Fan Liu Xiang-Hui Zou Juan Zhao Yu Huang Yu-Fan Zhu Zhao-Yu Li Chao Xu Li-Hua Luo Zhi-Qiang Luo Min-Hao Wu Lin Cai Xiao-Kun Li Zhou-Guang Wang Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research the Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000ZhejiangChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhou 325000ZhejiangChina department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan UniversityWuhan 430071China National Engineering Research Center for Nanomedicine College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China department of Overseas Education College Jimei UniversityXiamen 361021FujianChina School and Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325035ZhejiangChina

Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO3,PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO3into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusion:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,

关键词： Piezoelectric hydrogel Tissue engineering scafold Immunomodulation Angiogenesis Osteogenic differentiation

Proteomics techniques in protein biomarker discovery

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Quantitative Biology 2024年第1期12卷 53-69页

作者： Mahsa Babaei Soheila Kashanian Huang-Teck Lee Frances Harding department of Biology Faculty of ScienceRazi UniversityKermanshahIran Faculty of Chemistry Sensor and Biosensor Research Center(SBRC)Razi UniversityKermanshahIran Nanobiotechnology department Faculty of Innovative Science and TechnologyRazi UniversityKermanshahIran Centre for Marine Bioproducts Development Flinders UniversityAdelaideSouth AustraliaAustralia Monash Institute of pharmaceutical Sciences Monash UniversityMelbourneNew South WalesAustralia

Protein biomarkers represent specific biological activities and processes, so they have had a critical role in cancer diagnosis and medical care for more than 50 years. With the recent improvement in proteomics technologies, thousands of protein biomarker candidates have been developed for diverse disease states. Studies have used different types of samples for proteomics diagnosis. Samples were pretreated with appropriate techniques to increase the selectivity and sensitivity of the downstream analysis and purified to remove the contaminants. The purified samples were analyzed by several principal proteomics techniques to identify the specific protein. In this study, recent improvements in protein biomarker discovery, verification, and validation are investigated. Furthermore, the advantages, and disadvantages of conventional techniques, are discussed. Studies have used mass spectroscopy (MS) as a critical technique in the identification and quantification of candidate biomarkers. Nevertheless, after protein biomarker discovery, verification and validation have been required to reduce the false-positive rate where there have been higher number of samples. Multiple reaction monitoring (MRM), parallel reaction monitoring (PRM), and selected reaction monitoring (SRM), in combination with stable isotope-labeled internal standards, have been examined as options for biomarker verification, and enzyme-linked immunosorbent assay (ELISA) for validation.

关键词： biomarker discovery cancer biomarker gel-based methods gel-free methods mass spectroscopy proteomics

Deciphering the high-carbonization-temperature triggered enzymatic activity of wool-derived N,S-co-doped carbon nanosheets

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Chinese Chemical Letters 2024年第3期35卷 182-188页

作者： Jiachen Zhao Deshuai Yu Jianmin Chen Shihao Lin Yonghua Tang Chaoyu Fan Dongfang Zhou Youhui Lin department of Physics Research Institute for Biomimetics and Soft MatterFujian Provincial Key Laboratory for Soft Functional Materials ResearchXiamen UniversityXiamen 361005China School of Pharmacy and Medical technology Putian UniversityPutian 351100China Key Laboratory of Mental Health of the Ministry of Education NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Key Laboratory of pharmaceutical Analysis and Laboratory Medicine(Putian University) Fujian Province UniversityPutian 351100China

It is well-established that high carbonization temperature will trigger the enzyme-like activity of carbon-based materials.However,the catalytic mechanism is still ambiguous,which hinders the further rational design of nanomaterials as enzyme mimics.Hereby,N,S-rich carbonized wool nanosheets(CWs)were synthesized at different pyrolysis temperatures.As expected,only CWs treated with high-temperature possess intrinsic oxidase-and peroxidase-like activities.Meanwhile,density functional theory(DFT)calculations demonstrate that graphitic nitrogen and the co-existence of nitrogen and sulfur in the carbon matrix serve as the active sites for the enzyme-like process.More importantly,combining theoretical calculations and experimental observations,the high-temperature triggered catalytic mechanism can be ascribed to the fact that an appropriate high-temperature maximizes the graphitization degree to a certain extent,at which most of the catalytic active sites are well retained rather than evaporating.Moreover,coupling with excellent photothermal conversion efficiency and catalytic performance,CWs can be applied to photothermal-catalytic cancer therapy under near-infrared region(NIR)light irradiation.We believe this work will contribute to understanding the catalytic mechanism of carbon-based nanozymes and promote the development of new biomedical and pharmaceutical applications.

关键词： Carbon-based nanozyme Catalytic mechanism Density functional theory High-temperature carbonization

Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer

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Oncology Research 2024年第5期32卷 943-953页

作者： JIANBO ZHOU FENG WAN BIN XIAO XIN LI CHENG PENG FU PENG department of Pharmacology West China School of PharmacySichuan UniversityChengduChina State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese MedicineChengduChina Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologySichuan UniversityChengduChina Chengdu No.1 pharmaceutical Co. Ltd.PengzhouChina Chengdu Push Bio-technology Co. Ltd.ChengduChina

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

关键词： Metochalcone Breast cancer Lung cancer SASP JAK2/STAT3