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Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity

Signal Transduction and Targeted Therapy 2024年第1期9卷 259-270页

作者： Yan Sun Xiu-Na Yang Shuang-Shuang Yang Yi-Zhu Lyu Bing Zhang Kai-Wen Liu Na Li Jia-Chen Cui Guang-Xiang Huang Cheng-Lin Liu Jie Xu Jian-Qing Mi Zhu Chen Xiao-Hu Fan Sai-Juan Chen Shuo Chen Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Hematology Second Hospital of Dalian Medical UniversityDalian 116023China National Facility for Protein Science Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Legend Biotech China Nanjing 211112China Shanghai Immune Therapy Institute Shanghai Cancer InstituteState Key Laboratory of Oncogenes and Related GenesRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Wondercel Biotechnology Shenzhen 518052China

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular ***,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based *** co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple *** we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated *** analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in ***-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived *** results provide a framework for contemplating the AIM approach in designing next-generation CARs.

关键词： cytotoxicity Antigen elevated

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Er_(2)TiO_(5)@Ag nanocomposites:Enhanced photocatalysis and bacteria inactivation,and cytotoxicity

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Journal of Rare Earths 2024年第5期42卷 851-858,I0002页

作者： Mehdi Nazeri Hossein Sedaghat Reza Rafiei Mohammad Amin Farzin Seyed Mostafa Hosseinpour Mashkani Department of Parasitology and Mycology Kashan University of Medical SciencesKashanIran Department of Microbiology Kashan University of Medical SciencesKashanIran General Medicine Student School of MedicineKashan University of Medical SciencesKashanIran Student Research Committee Kashan University of Medical SciencesKashanIran Institute for Biomedical Materials and Devices School of Mathematical and Physical SciencesFaculty of ScienceUniversity of Technology SydneyNSW2007Australia

In this study,we successfully synthesized Er_(2)TiO_(5)@Ag nanocomposites(NCPs) using the ultrasonicmediated sol-gel technique to create a multifunctional material with enhanced photocatalytic and antibacterial *** visible light photocatalytic activities of Er_(2)TiO_(5) nanoparticles(NPs) and Er_(2)TiO_(5)@Ag NCPs were systematically evaluated under various conditions,including different concentrations of Basic Blue 41(BB 41) dye and *** results reveal a remarkable improvement in the photocatalytic degradation efficiency of Er_(2)TiO_(5)@Ag NCPs(95%) compared to Er_(2)TiO_(5) NPs(80%).Furthermore,the antibacterial efficacy of Er_(2)TiO_(5) NPs and Er2TiO_5@Ag NCPs were extensively examined against Gram-positive and Gram-negative ***,Er_(2)TiO_(5)@Ag NCPs exhibit significantly higher minimum bactericidal concentration(MBC) values compared to Er_(2)TiO_(5) *** antibacterial effect of Er_(2)TiO_(5)@Ag NCPs is particularly pronounced against *** and Pseudomonas aeruginosa,while demonstrating moderate effects on Escherichia coli and Enterococcus *** assess the biocompatibility of the synthesized materials,we investigated their internalization by MCF-7 ***,both Er_(2)TiO_(5) NPs and Er_(2)TiO_(5)@Ag NCPs are found to be effectively internalized by the cells,suggesting their potential application in biomedical ***,our study unveils the exceptional potential of Er_(2)TiO_(5)@Ag NCPs as a dual-action solution,simultaneously possessing enhanced photocatalytic efficiency and potent antibacterial *** multifunctional nanocomposite not only outperforms Er_(2)TiO_(5) and Ag but also paves the way for innovative applications in sustainable environmental remediation and advanced biomedical technologies,promising a brighter and cleaner future.

关键词： Rare earth catalysis Nanocomposite Er_(2)TiO_(5)@Ag Antibacterial activity Photocatalysis cytotoxicity

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Antibacterial mechanism with consequent cytotoxicity of different reinforcements in biodegradable magnesium and zinc alloys: A review

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Journal of Magnesium and Alloys 2023年第9期11卷 3038-3058页

作者： Chowdhury Ahmed Shahed Faiz Ahmad Ebru Günister Farhana Mohd Foudzi Saad Ali Khurshid Malik Wan Sharuzi Wan Harun Department of Mechanical Engineering Universiti Teknologi PETRONAS(UTP)32610Seri IskandarPerakMalaysia Faculty of Engineering and Natural Sciences Department of Mechanical EngineeringIstanbul Health and Technology UniversityIstanbulTurkey Department of Mechanical and Manufacturing Engineering Faculty of Engineering and Built EnvironmentUniversiti Kebangsaan Malaysia43600 UKM BangiSelangorMalaysia Faculty of Mechanical&Automotive Engineering Technology Universiti Malaysia Pahang26600 PekanPahangMalaysia

Benefits achieved by the biodegradable magnesium(Mg) and zinc(Zn) implants could be suppressed due to the invasion of infectious microbial, common bacteria, and fungi. Postoperative medications and the antibacterial properties of pure Mg and Zn are insufficient against biofilm and antibiotic-resistant bacteria, bringing osteomyelitis, necrosis, and even death. This study evaluates the antibacterial performance of biodegradable Mg and Zn alloys of different reinforcements, including silver(Ag), copper(Cu), lithium(Li), and gallium(Ga). Copper ions(Cu^(2+)) can eradicate biofilms and antibiotic-resistant bacteria by extracting electrons from the cellular structure. Silver ion(Ag^(+)) kills bacteria by creating bonds with the thiol group. Gallium ion(Ga^(3+)) inhibits ferric ion(Fe^(3+)) absorption, leading to nutrient deficiency and bacterial death. Nanoparticles and reactive oxygen species(ROS) can penetrate bacteria cell walls directly, develop bonds with receptors, and damage nucleotides. Antibacterial action depends on the alkali nature of metal ions and their degradation rate, which often causes cytotoxicity in living cells. Therefore, this review emphasizes the insight into degradation rate, antibacterial mechanism, and their consequent cytotoxicity and observes the correlation between antibacterial performance and oxidation number of metal ions.

关键词： Biodegradable materials Biomedical implants Antibacterial mechanism cytotoxicity Reactive oxygen species

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Wear Resistance, cytotoxicity and Antibacterial Properties of Polyetheretherketone Composite Modified by Carbon Fiber and Black Phosphorus

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Journal of Bionic Engineering 2022年第1期19卷 155-166页

作者： Jingdan Li Qian Liang Wen Qin Jing Ma School of Material Science and Engineering Taiyuan University of TechnologyTaiyuan030024China

High wear resistance,low cytotoxicity and excellent antibacterial properties are the basis for osseointegration of implant ***(PEEK)has been considered as a potential implant material due to its excellent biocompatibility,natural radiolucency and mechanical *** this work,to improve the wear resistance,cytotoxicity and antibacterial properties of PEEK,carbon fiber(CFR)and Black Phosphorus(BP)were used to synergistically modify PEEK by two methods,deposition of BP coating on CFR-PEEK and BP/CFR-PEEK coating on Ti6Al4V(TC4)through electrostatic *** CFR and BP synergistically modified PEEK,the friction coefficient of BP coating on CFR-PEEK and BP/CFR-PEEK coating were 0.14±0.01 and 0.09±0.02,*** wear volume of BP coating on CFR-PEEK(30.54±1.32)was higher than that of BP/CFR-PEEK coating(9.46±1.32),which indicated that BP/CFR-PEEK coating showed high wear *** difference in wear resistance may be caused by the fact that BP was not easily oxidized in BP/CFR-PEEK *** addition,BP coating on CFR-PEEK and BP/CFR-PEEK coating showed no obvious cytotoxicity to L929 cell and presented excellent antibacterial efficiency(up to 94.5%±2.8%and 96.0%±3.8%,respectively)against Staphylococcus aureus(***).It was concluded that BP/CFR-PEEK coating exhibited high wear resistance,low cytotoxicity and excellent antibacterial properties against ***,which might provide a foundation for osseointegration of implants.

关键词： Surface deposition Electrostatic spraying Wear resistance cytotoxicity Antibacterial properties

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Echinoside A from Pearsonothuria graeffei Exert the cytotoxicity to MDA-MB-231 Cells via Mitochondrial Membrane and Modulation of PI3K/Akt/mTOR Pathway

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Journal of Ocean University of China 2023年第1期22卷 205-212页

作者： LI Hongyan CUI Huanhuan CONG Peixu XU Jie XIE Wancui WANG Yuming XUE Changhu College of Marine Science and Biological Engineering Qingdao University of Science and TechnologyQingdao 266042China College of Food Science and Engineering Ocean University of ChinaQingdao 266003China

A kind of triterpene glycosides echinoside A(EA)was extracted from sea cucumber Pearsonothuria graeffei,and its yield was about 0.78%.The purity of EA was 99.0%,and its molecular weight was 1206 *** was a linear tetrasaccharide attached to a pentacyclic triterpene *** inhibited the growth of MDA-MB-231 cells in *** antitumor effect was related to elevate ROS level,decrease mitochondrial membrane potential,enhance caspase-3 expression,induce cells apoptosis and arrest cell cycle at G2/M *** also dose-dependently suppressed the expressions of phophorylation proteins p-PI3K,p-Akt,and p-mTOR as analyzed by western *** results suggested that EA caused MDA-MB-231 cells apoptosis via intrinsic mitochondrial and PI3K/Akt/mTOR *** can be a potential anti-breast cancer agent to enhance the clinical efficacy.

关键词： Pearsonothuria graeffei echinoside A cytotoxicity PI3K/Akt/mTOR pathway

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cytotoxicity,Degradation and Release Behavior of Alginate Fibers Loaded with Chlorhexidine Gluconate and Its Docking Simulation

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Journal of Harbin Institute of Technology(New Series) 2022年第5期29卷 49-56页

作者： Songsong Shi Yuting Chen Xinke Xia Yuan'e Zhang Minlu Feng Shengjiao Lei College of Biological and Pharmaceutical China Three Gorges UniversityYichang 443002HubeiChina

To investigate the feasibility and safety of alginate fibers loaded with chlorhexidine gluconate(CHG)for biomedical applications,vitro cytotoxic test and drug release pattern were *** Studio(DS),a computer aided software,was utilized to briefly investigate the energy state and solvation at the molecular *** fiber loaded with CHG presented different drug release patterns in PBS and A *** results indicated that CHG-loaded alginate fibers can promote the growth of L-929 mouse fibroblast cells with better *** the simulation,the lowest energy conformation of three representative molecular bond regions was optimized with stronger *** the torsional energy increased,the bond energy of the target regions ***,the transition energy of the target regions was greatly reduced by *** a word,alginate fibers loaded with CHG expressed better biocompatibility and drug sustained-release ability,which indicates that CHG-loaded alginate fibers has a broad application prospect in medical dressing.

关键词： alginate medical polymer molecular docking cytotoxicity drug release

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cytotoxicity and Apoptosis Assay of Novel Cyclomyrsinol Diterpenes Against Breast Cancer Cell Lines

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World Journal of Traditional Chinese Medicine 2022年第2期8卷 273-277页

作者： Faezeh Rabbani Zeinab Yazdiniapour Mustafa Ghanadian Behzad Zolfaghari Melika Maleki Fatemeh Shafiee Pharmacy Student’s Research Committee School of PharmacyIsfahan University of Medical Sciences Department of Pharmacognosy School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical Sciences Department of Pharmaceutical Biotechnology School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran

Background:Cyclomyrsinane diterpenes especially those extracted from various Euphorbia species have shown interesting biological properties in recent *** of the high prevalence of breast cancer and the challenges ahead in its treatment,the use of these compounds as potential anti cancer agents seem ***:The aim of the present study was to evaluate the cytotoxic effects of some myrsinane type diterpenoids extracted from Euphorbia sogdiana Popov and determine their induced cell death ***:MTT assay was used to determine the cytotoxicity of six various myrsinane compounds on MCF 7 and 4 T1 breast cancer cell *** umbilical vein endothelial cells were used as the normal cell line *** apoptotic effects of the structure with the most cytotoxic effects were determined using flow cytometry assay in IC50 concentration for 24 h of ***:Compound(6)showed the most cytotoxic effects with IC50 of about 8±4 and 24±4μg/mL for MCF 7 and 4 T1 cell lines,***,the cells treated with 5 and 10μg/mL of compound(6)for 24 h,showed 37 and 55%of apoptotic ***:These surveyed compounds have the potential to be considered as useful anti-breast cancer agents due to the great cytotoxicity and apoptotic effects against these cancer cells and the fact that there was no significant cytotoxicity on normal cells.

关键词： Apoptosis breast cancer cyclomyrsinol diterpenoids cytotoxicity Euphorbia sogdiana Popov

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Bioactive glass selectively promotes cytotoxicity towards giant cell tumor of bone derived neoplastic stromal cells and induces MAPK signalling dependent autophagy

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Bioactive Materials 2022年第9期7卷 456-468页

作者： Joerg Fellenberg Sarina Losch Burkhard Lehner Marcela Arango-Ospina Aldo RBoccaccini Fabian Westhauser Center for Orthopedics Trauma Surgery and Spinal Cord InjuryHeidelberg University HospitalHeidelbergGermany Institute of Biomaterials Department of Materials Science and EngineeringUniversity of Erlangen-NurembergGermany

Giant cell tumors of bone(GCTB)are associated with massive bone destructions and high recurrence *** a previous study,we observed cytotoxic effects of three different compositions of bioactive glasses(BGs)towards GCTSC but not bone marrow derived stromal cells(BMSC)indicating that BGs represent promising candidates for the development of new therapeutic *** the current study we aimed to investigate the molecular mechanisms that are involved in BG induced *** observed,that BG treatment was not associated with any signs of apoptosis,but rather led to a strong induction of mitogen activated protein kinases(MAPK)and,as a consequence,upregulation of several transcription factors specifically in *** wide gene expression profiling further revealed a set of fifteen genes that were exclusively induced in GCTSC or induced significantly stronger in GCTSC compared to *** treatment further induced autophagy that was significantly more pronounced in GCTSC compared to BMSC and could be inhibited by MAPK *** with the known osteogenic properties of BGs our findings support the suitability of BGs as therapeutic agents for the treatment of ***,these data have to be verified under in vivo conditions.

关键词： Bioactive glass Giant cell tumor of bone Mesenchymal stromal cells Mitogen-activated protein kinases cytotoxicity Autophagy

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NK cell dysfunction in severe COVID-19:TGF-β-induced downregulation of integrin beta-2 restricts NK cell cytotoxicity

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Signal Transduction and Targeted Therapy 2022年第2期7卷 346-348页

作者： Joana Barros-Martins Reinhold Förster Berislav Bošnjak Institute of Immunology Hannover Medical School30625 HannoverGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical School30625 HannoverGermany German Centre for Infection Research(DZIF) Partner site HannoverHannoverGermany

In a recent study published in Nature,Witkowski et *** that in patients with severe forms of coronavirus disease 2019(COVID-19)deranged tumor growth factor-beta(TGF-β)secretion counteracts interferon-alpha(IFN-α)-induced activation of NK cells by decreasing expression of transcription factor ***,NK cells fail to upregulate the adhesion molecule integrin beta-2(-ß2),which impedes their attachment to and killing of SARS-CoV-2 infected cells.

关键词： interferon cytotoxicity

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Metabolic interaction:tumor-derived lactate inhibiting CD8^(+)T cell cytotoxicity in a novel route

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Signal Transduction and Targeted Therapy 2023年第3期8卷 874-876页

作者： Ke Wang Yong Zhang Zhi-Nan Chen National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi’an710032China Department of Pulmonary and Critical Care Medicine the First Affiliated Hospital of Fourth Military Medical UniversityXi’an710032China

Recently,an interesting study published in Cell Metabolism discovered a novel metabolic interaction between tumors and T cells,identifying that tumor-derived lactate inhibited CD8^(+)T cell cytotoxicity by inducing a switch of pyruvate utilization from pyruvate carboxylase(PC)to pyruvate dehydrogenase(PDH),and PDH inhibition facilitated PC activity and T cell cytotoxicity through increasing succinate secretion.

关键词： cytotoxicity inhibited inhibiting

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