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Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

Engineering 2024年第5期36卷 178-192页

作者： Ruogu Qi Shanshan Wang Jiayi Yu Tianming Lu Zhiqiang Bi Weibo Liu Yuanyuan Guo Yong Bian Jianliang Shen Xuesong Zhang Wenhao Hu School of Medicine Nanjing University of Chinese MedicineNanjing 210023China Laboratory Animal Center Nanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Carcinogenesis and translational Research Ministry of Education/BeijingDepartment of Radiation OncologyBeijing Cancer HospitalBeijing 100142China Department of Orthopedics The Fourth Medical CenterThe Chinese People’s Liberation Army General HospitalBeijing 100853China State Key Laboratory of Ophthalmology Optometry and Vision ScienceSchool of Biomedical EngineeringWenzhou Medical UniversityWenzhou 325027China

Multiple myeloma(MM)is the second most prevalent hematological *** MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic *** study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@*** results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in ***,this material demonstrated a capability for drug release triggered by low pH ***,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM ***,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic ***,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

关键词： Multiple myeloma Bortezomib Drug delivery Dual targeting Controlled release

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Differences in clinicopathological characteristics between lipohypertrophy and localized insulin-derived amyloidosis:A scoping review

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Chronic Diseases and translational Medicine 2024年第1期10卷 22-30页

作者： Kanae Mukai Hiromasa Tanno Junko Sugama Toshihiko Yanagita Emi Kanno Department of Clinical Nursing Faculty ofHealth SciencesInstitute of MedicalPharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan Department of translational science forNursing Tohoku University Graduate School ofMedicineSendaiJapan Research Center for Implementation Nursingscience Initiative School of Health SciencesFujita Health UniversityToyoakeJapan Department of Clinical Pharmacology Schoolof NursingUniversity of MiyazakiMiyazakiJapan

Insulin is used as a therapeutic agent in patients with diabetes,and cutaneous lipohypertrophy(LH)and localized insulin-derived amyloidosis(LIDA)are well-known adverse effects associated with insulin *** clinical implications,management,assessment methods,and pathological differentiation of LH and LIDA have been recently *** review was to update our knowledge of the pathological differentiation,effects of insulin absorption,hypoglycemic events,and recent assessment methods for LH and LIDA.A scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews *** studies and case reports in English were also *** and Scopus databases were searched for keywords to identify papers published up to January 2022.A total of 113 studies were identified through a database search,and 31 were eligible for inclusion in this scoping *** the 31 studies included in this review,patients with type 2 diabetes had high frequencies of LH and *** outcome parameters were assessed using pathological findings and *** is mainly determined by pathological methods,such as hematoxylin and eosin and Congo red *** in vitro and in vivo LIDA models of LIDA have been *** results suggest that pathological analysis is required to identify LH and *** is important to consider LIDA,as it likely influences insulin adsorption and glycemic *** several studies have evaluated the LIDA process,little is known about the mechanisms underlying the development of adverse effects associated with insulin injections.

关键词： diabetes mellitus insulin injection lipohypertrophy localized insulin-derived amyloidosis

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An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβblockade therapy

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3594-3601页

作者： Robert Pomponio Qi Tang Anthony Mei Anne Caron Bema Coulibaly Joachim Theilhaber Maximilian Rogers-Grazado Michele Sanicola-Nadel Souad Naimi Reza Olfati-Saber Cecile Combeau Jack Pollard Tun Tun Lin Rui Wang sanofi translational Medicine Early Development Cambridge MA 02142USA sanofi Artificial Intelligence and Deep Analytics Data and Data sciences CambridgeMA 02142USA sanofi translational science Vitry sur Seine 94403France sanofi Precision Oncology Cambridge MA 02142USA sanofi Oncology Early Development Cambridge MA 02142USA

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes(TILs)is associate with response to *** studies have identified TGFβactivity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 *** we coupled the artificial intelligence(AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGFβpathway *** of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution *** digital image analysis approach achieves 74%concordance with the pathologist assessment for tumor-immune *** transcriptomic profiling suggests that the TIL score was negatively correlated with TGFβpathway activation,together with elevated TGFβsignaling activity observed in excluded and desert tumor *** present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes:immune desert,immune excluded or immune *** association between“cold”tumor-immune phenotypes and TGFβsignature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGFβblockade.

关键词： Digital pathology Artificial intelligence TGFβ Predictive biomarker Tumor topography T cell infiltration Transcriptomic profiling Machine learning

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Apple polyphenol phloretin inhibits type II glucose transporter and enhances anti-HER2 antibody drug binding as an adjuvant treatment for HER2-positive breast cancer

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Food science and Human Wellness 2024年

作者： Han-Sheng Chang Tzu-Chun Cheng Shih-Hsin Tu Pei-Han Liao Yu-Ching Lee Chi-Tang Ho Min-Hsiung Pan Li-Ching Chen Yuan-Soon Ho Department of Biological science & Technology， College of Life sciences， China Medical University Institute of Biochemistry and Molecular Biology， College of Life sciences， China Medical University Department of Surgery， School of Medicine， College of Medicine， Taipei Medical University Research Center of Cancer translational Medicine， Taipei Medical University Department of Food science， Rutgers University New Jersey， USA Institute of Food sciences and Technology， Taiwan University

This study presents novel findings on the potential of phloretin， an apple polyphenol， to enhance the effectiveness of anti-HER2 antibody therapy in HER2-positive breast cancer patients. Our research reveals that phloretin inhibits type II glucose transporter (GLUT2) activity， significantly reducing cancer cell glucose uptake. We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues， with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients. Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins， attenuate glycolysis， and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells. Furthermore， the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft (CDX) tumor animal model， particularly in suppressing the growth of Trastuzumab-resistant HER2+ breast cancer. These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer， offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.

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Mitochondria-targeted carrier-free nanoparticles based on dihydroartemisinin against hepatocellular carcinoma

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Chinese Chemical Letters 2024年第10期35卷 355-359页

作者： Zhiyu Yu Xiang Luo Cheng Zhang Xin Lu Xiaohui Li Pan Liao Zhongqiu Liu Rong Zhang Shengtao Wang Zhiqiang Yu Guochao Liao Joint Laboratory for translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China International Institute for Translational Chinese Medicine Guangzhou University of Chinese Medicine Guangzhou Yuemei Pharmaceutical Technology Co. Ltd. Affiliated Foshan Maternity & Child Healthcare Hospital Southern Medical University School of Pharmaceutical sciences Southern Medical University Department of Laboratory Medicine Dongguan Institute of Clinical Cancer Research Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital)

Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy. Dihydroartemisinin(DHA), a derivative of artemisinin, has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS) and resultant mitochondrial damage. However, clinical translation is limited by several drawbacks, such as insolubility, instability and low bioavailability. Here, based on a nanomedicine-based delivery strategy, we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP), aiming to improve bioavailability and mitochondrial targeting. DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized. Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS, which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway, leading to apoptosis. In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma. These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.

关键词： Apoptosis Carrier-free nanoparticles Dihydroartemisinin Hepatocellular carcinoma Mitochondria targeting

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Naked-eye visualization of lymph nodes using fluorescence nanoprobes in non-human primate-animal models

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Nano Research 2024年第8期17卷 7404-7414页

作者： Xiaoyuan Ji Binbin Chu Xiaofeng Wu Zhiming Xia Airui Jiang Chenyu Wang Zhiming Chen Danni Zhong Qiaolin Wei Bin Song Wanlin Li Yiling Zhong Houyu Wang Fenglin Dong Min Zhou Yao He Suzhou Key Laboratory of Nanotechnology and Biomedicine Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesInstitute of Functional Nano and Soft Materials(FUNSOM)Soochow UniversitySuzhou 215123China School of Public Health Shanghai Jiao Tong University School of MedicineShanghai 200025China Zhejiang University-University of Edinburgh Institute(ZJU-UoE Institute) Zhejiang UniversityHaining 314400China Department of Ultrasound the First Affiliated Hospital of Soochow UniversitySuzhou 215006China State Key Laboratory(SKL)of Biobased Transportation Fuel Technology Zhejiang UniversityHangzhou 310027China School of Pharmacy Hangzhou Normal UniversityHangzhou 311121China Macao translational Medicine Center Macao University of Science and TechnologyTaipa 999078MacaoChina Macao Institute of Materials science and Engineering Macao University of Science and TechnologyTaipa 999078MacaoChina

Despite sufficient studies performed in non-primate animal models,there exists scanty information obtained from pilot trials in non-human primate animal models,severely hindering nanomaterials moving from basic research into clinical *** herein present a pioneering demonstration of nanomaterials based optical imaging-guided surgical operation by using macaques as a typical kind of non-human primate-animal ***,taking advantages of strong and stable fluorescence of the small-sized(diameter:~5 nm)silicon-based nanoparticles(SiNPs),lymphatic drainage patterns can be vividly visualized in a real-time manner,and lymph nodes(LN)are able to be sensitively detected and precisely excised from small animal models(e.g.,rats and rabbits)to non-human primate animal models(e.g.,cynomolgus macaque(Macaca fascicularis)and rhesus macaque(Macaca mulatta)).Compared to clinically used invisible near-infrared(NIR)lymphatic tracers(i.e.,indocyanine green(ICG);etc.),we fully indicate that the SiNPs feature unique advantages for naked-eye visible fluorescence-guided surgical operation in long-term *** toxicological analysis in macaque models further provides confirming evidence of favorable biocompatibility of the SiNPs *** expect that our findings would facilitate the translation of nanomaterials from the laboratory to the clinic,especially in the field of cancer treatment.

关键词： fluorescent silicon nanoparticles lymph node real-time naked-eye visualization macaque models

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Early and Sensitive Detection of Pathogens for Public Health and Biosafety:An Example of Surveillance and Genotyping of SARS-CoV-2 in Sewage Water by Cas12a-Facilitated Portable Plasmonic Biosensor

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Research 2024年第2期2023卷 259-272页

作者： Tianzhong Li Yuzhi Chen Zhi Chen Yuan Hao Minyi Liang Yingxia Liu Guanyong Ou Huanian Zhang Yuxuan Tang Yabing Hao Swelm Wageh Omar AAl-Hartomy Abul Kalam Bin Zhang Xin Shi Xuejin Li Han Zhang College of Physics and Optoelectronic Engineering Institute of Translational MedicineDepartment of OtolaryngologyShenzhen Second People's HospitalFirst Affiliated Hospital of Shenzhen UniversityHealth Science CenterShenzhen UniversityShenzhen 518060China Shenzhen Key Laboratory of Sensor Technology Shenzhen 518060China The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan People's HospitalQingyuan 511518China Shenzhen Key Laboratory of Pathogen and Immunity National Clinical Research Center for Infectious DiseaseState Key Discipline of Infectious DiseaseShenzhen Third People's HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China School of Medicine Southern University of Science and TechnologyShenzhen 518055China School of Physics and Optoelectronic Engineering Shandong University of TechnologyZibo 255049China Department of Physics Faculty of ScienceKing Abdulaziz University Jeddah 21589Saudi Arabia Research Center for Advanced Materials science(RCAMS) King Khalid UniversityP.0.Box 9004Abha 61413Saudi Arabia Department of Chemistry College of ScienceKing Khalid UniversityP.0.Box9004Abha 61413 Saudi Arabia Health sciences Institute China Medical UniversityShenyang 110000China The Chinese University of Hong Kong Shenzhen 518060China

Infectious diseases severely threaten public health and global *** addition to transmission through the air,pathogenic microorganisms have also been detected in environmental liquid samples,such as sewage *** biochemical detection methodologies are time-consuming and cost-ineffective,and their detection limits hinder early *** the present study,ultrafine plasmonic fiber probes with a diameter of 125μm are fabricated for clustered regularly interspaced short palindromic repeats/CRISPR-associated protein(CRISPR/Cas)-12a-mediated sensing of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Single-stranded DNA exposed on the fiber surface is trans-cleaved by the Cas12a enzyme to release gold nanoparticles that are immobilized onto the fiber surface,causing a sharp reduction in the surface plasmon resonance(SPR)*** proposed fiber probe is virus-specific with the limit of detection of~2,300 copies/ml,and genomic copy numbers can be reflected as shifts in wavelengths.A total of 21 sewage water samples have been examined,and the data obtained are consistent with those of quantitative polymerase chain reaction(qPCR).In addition,the Omicron variant and its mutation sites have been fast detected using S gene-specific *** study provides an accurate and convenient approach for the real-time surveillance of microbial contamination in sewage water.

关键词： fiber consuming hinder

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Super Resolution Fluorescence Microscopy for Cilia Investigation and Ciliopathy Diagnosis

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激光与光电子学进展 2024年

作者： Zhen LIU Yang WU Division of Life science The Hong Kong University of Science and Technology

The last two decades have witnessed the invention and development of superresolution microscopy(SRM), which breaks the diffraction limit of light and pushes the resolution of fluorescence microscopy to several nanometers. SRM is now widely applied in biological studies such as resolving subdiffraction structures, molecular mapping, single molecule tracking, probing protein-protein interactions, and observing organelle dynamics. However, its direct application in translational medicine such as disease diagnosis is still preliminary. Despite their small size, cilia play a crucial role as organelles in cell signaling and motility, and defects in cilia lead to ciliopathy. Like other miniature organelles and macromolecular complexes, cilia are ideal for superresolution imaging. In this review, we will 1) introduce cilia and ciliopathy, 2) show how SRM extends our knowledge of cilia, and 3) focus on how SRM improves the diagnosis of motile ciliopathies.

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Hierarchical Self-assembly of Atomically Precise Au Nanoclusters with Molecular Rotor-based Ligands

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Chemical Research in Chinese Universities 2024年第4期40卷 670-674页

作者： WANG Guanzhong LU Hui LI Jiang WANG Lihua ZHU Ying SONG Shiping GE Zhilei LI Qian CHEN Jing FAN Chunhai Division of Physical Biology Shanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai201800P.R.China University of Chinese Academy of sciences Beijing100049P.R.China Zhangjiang Laboratory Shanghai201210P.R.China Institute of Materiobiology Department of ChemistryCollege of SciencesShanghai UniversityShanghai200444P.R.China School of Chemistry and Chemical Engineering New Cornerstone Science LaboratoryFrontiers Science Center for Transformative MoleculesZhangjiang Institute for Advanced Study and National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai200240P.R.China

The hierarchical assemblies of precise nanoparticles(NPs)have created materials with emergent properties and ***,the complex assemblies remain unclear at a precise ***,we show the hierarchical self-assembly of atomically precise gold nanoclusters(Au NCs)with molecular rotor-based ligands(MRL),featuring a double-layer *** to two other types of monolayer-protected(MLP)Au NCs,the significantly reduced surface density for MRL Au NCs profoundly influences their assembly behavior within the ***,the long length of rotor-based ligands and the rotational freedom of the phenyl-rings of rotor-based ligands also facilitate the assembly of *** works elucidate the hierarchical assembly on a precise scale,suggesting that the rotor-based ligand’s strategy offers promising potential for designing well-defined and more complex structures in supercrystals.

关键词： Gold nanocluster Molecular rotor Hierarchical assembly Double-layer surface

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Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin‑producing *** challenged weaned piglets

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Journal of Animal science and Biotechnology 2024年第3期15卷 1278-1291页

作者： Matthias Dierick Ruben Ongena Daisy Vanrompay Bert Devriendt Eric Cox Laboratory of Immunology Department of Translational PhysiologyInfectiology and Public HealthFaculty of Veterinary MedicineGhent UniversitySalisburylaan 1339820 MerelbekeBelgium Laboratory for Immunology and Animal Biotechnology Faculty of Bioscience EngineeringGhent UniversityCoupure links 6539000 GhentBelgium

Background Post-weaned piglets suffer from F18+Escherichia coli(***)infections resulting in post-weaning diar-rhoea or oedema *** used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial *** antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being *** has shown promising results against porcine enterotoxigenic *** strains,both in vitro and in *** We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned ***,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing ***(STEC)***,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC *** did not affect theα-andβ-***,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal *** analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF *** Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned ***,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut ***,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.

关键词： E.coli Immune modulation Lactoferrin Microbiome

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