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Engineering H2O2 Self-Supplying Platform for Xdynamic Therapies via Ru-Cu Peroxide Nanocarrier: Tumor Microenvironment-Mediated Synergistic Therapy

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ACS Applied Materials and Interfaces 2024年第19期16卷 24172-24190页

作者： Dirersa, Worku Batu Kan, Tzu-Chun Chang, Jungshan Getachew, Girum Ochirbat, Sonjid Kizhepat, Shamsa Wibrianto, Aswandi Rasal, Akash Chen, Hung-An Ghule, Anil Vithal Chou, Tzung-Han Chang, Jia-Yaw Department of Chemical Engineering National Taiwan University of Science and Technology Taipei106335 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan International Master/Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Green Nanotechnology Laboratory Department of Chemistry Shivaji University Kolhapur416004 India Department of Chemical and Materials Engineering National Yunlin University of Science and Technology Yunlin64002 Taiwan

Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient H2O2 concentration in the tumor microenvironment (TME) are the main barriers to the advancment of reactive oxygen species (ROS) mediated Xdynamic therapies (X = photo, chemodynamic, chemo). Maximizing Fenton catalytic efficiency is crucial in chemodynamic therapy (CDT), yet endogenous H2O2 levels are not sufficient to attain better anticancer efficacy. Specifically, there is a need to amplify Fenton reactivity within tumors, leveraging the unique attributes of the TME. Herein, for the first time, we design RuxCu1-xO2-Ce6/CPT (RCpCCPT) anticancer nanoagent for TME-mediated synergistic therapy based on heterogeneous Ru-Cu peroxide nanodots (RuxCu1-xO2 NDs) and chlorine e6 (Ce6), loaded with ROS-responsive thioketal (TK) linked-camptothecin (CPT). The Ru-Cu peroxide NDs (RCp NDs, x = 0.50) possess the highest oxygen vacancy (OV) density, which grants them the potential to form massive Lewis’s acid sites for peroxide adsorption, while the dispersibility and targetability of the NDs were improved via surface modification using hyaluronic acid (HA). In TME, RCpCCPT degrades, releasing H2O2, Ru2+/3+, and Cu+/2+ ions, which cooperatively facilitate hydroxyl radical (•OH) formation and deactivate antioxidant GSH enzymes through a cocatalytic loop, resulting in excellent tumor therapeutic efficacy. Furthermore, when combined with laser treatment, RCpCCPT produces singlet oxygen (1O2) for PDT, which induces cell apoptosis at tumor sites. Following ROS generation, the TK linkage is disrupted, releasing up to 92% of the CPT within 48 h. In vitro investigations showed that laser-treated RCpCCPT caused 81.5% cell death from PDT/CDT and chemotherapy (CT). RCpCCPT in cancer cells produces red-blue emission in images of cells taking them in, which allows for fluorescence image-guided Xdynamic treatment. The overall results show that RCp NDs and RCpCCPT are more biocompatible and have excellent Xdynamic the

关键词： Oxidation

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The hens guarding epithelial cancer fox-houses

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细胞研究（英文版） 2022年第3期32卷 225-226页

作者： Liam T.Gaynor Ramesh A.Shivdasani Department of Medical Oncology Dana-Farber Cancer InstituteBostonMAUSA Graduate Program in Biological&Biomedical Sciences Harvard Medical SchoolBostonMAUSA Department of Medical Oncology Dana-Farber Cancer InstituteBostonMAUSA Department of Medicine Harvard Medical SchoolBostonMAUSA Harvard Stem Cell Institute CambridgeMAUSA

Esophageal micro-tumors that form rapidly in a carcinogen-induced mouse model regress almost as fast.

关键词： Oesophageal cancer Life Sciences general cell Biology

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Mutational and biophysical analyses reveal a TFIIIC binding region in the TFIIF-related Rpc53 subunit of RNA polymerase III (vol 299, 105041 , 2023)

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JOURNAL OF BIOLOGICAL CHEMISTRY 2023年第8期299卷 104859页

作者： Shekhar, Arvind Chandra Wu, Wen-Jin Chen, Hung-Ta Molecular and Cell Biology Taiwan International Graduate Program Graduate Institute of Life Sciences National Defense Medical Center Taipei Taiwan R.O.C. Institute of Molecular Biology Academia Sinica Taipei Taiwan R.O.C. Institute of Biological Chemistry Academia Sinica Taipei Taiwan R.O.C.

The TFIIF-like Rpc53/Rpc37 heterodimer of RNA polymerase (pol) III is involved in various stages of transcription. The C-terminal region of Rpc53 dimerizes with Rpc37 to anchor on the lobe domain of the pol III cleft. However, structural and functional features of the Rpc53 N-terminal region had not been characterized previously. Here, we conducted site-directed alanine replacement mutagenesis on the Rpc53 N-terminus, generating yeast strains that exhibited a cold-sensitive growth defect and severely compromised pol III transcriptional activity. Circular dichroism and NMR spectroscopy revealed a highly disordered 57-amino acid polypeptide in the Rpc53 N-terminus. This polypeptide is a versatile protein-binding module displaying nanomolar-level binding affinities for Rpc37 and the Tfc4 subunit of the transcription initiation factor TFIIIC. Accordingly, we denote this Rpc53 N-terminus polypeptide as the TFIIIC-binding region or CBR. Alanine replacements in the CBR significantly reduced its binding affinity for Tfc4, highlighting its functional importance to cell growth and transcription in vitro. Our study reveals the functional basis for Rpc53’s CBR in assembly of the pol III transcription initiation complex.

关键词： transcription RNA polymerase III Rpc53 Rpc25 Rpc17 TFIIIC Tfc4 microscale thermophoresis

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Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healing

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Genes & Diseases 2022年第4期9卷 841-844页

作者： Shang Jiunn Chuah Chee Weng Yong Kristeen Ye Wen Teo Jacob Ren Jie Chew Yi Ann Cheow Shipin Zhang Raymond Chung Wen Wong Asher Ah Tong Lim Sai Kiang Lim Wei Seong Toh Faculty of Dentistry National University of Singapore119085Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research138648Singapore Department of Orthopaedic Surgery Yong Loo Lin School of MedicineNational University of Singapore119288Singapore Department of Biomedical Engineering Faculty of EngineeringNational University of Singapore117583Singapore Tissue Engineering Program Life Sciences InstituteNational University of Singapore117456Singapore Integrative Sciences and Engineering Program NUS Graduate SchoolNational University of Singapore119077Singapore

Mesenchymal stem/stromal cells(MSCs)have demonstrated therapeutic efficacy for bone regeneration in animal and clinical *** MSCs were initially thought to differentiate to various cell types to replace the injured/diseased tissue,it is now accepted that these cells secrete factors to promote tissue repair.1 Among these factors,small extracellular vesicles(sEVs)of size 50–200 nm,which include the exosomes,have been identified as the principal agent mediating the wide-ranging therapeutic efficacy of MSCs.2 Several studies have also reported the therapeutic effects of MSC-sEVs to enhance bone repair in animal models,as recently reviewed.3 However,the cellular processes and mechanisms mediated by MSC-sEVs in bone regeneration remain to be fully elucidated.

关键词： healing clinical macrophage

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Effect of loops on the mean-square displacement of Rouse-model chromatin

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Physical Review E 2024年第4期109卷 044502-044502页

作者： Tianyu Yuan Hao Yan Mary Lou P. Bailey Jessica F. Williams Ivan Surovtsev Megan C. King Simon G. J. Mochrie Integrated Graduate Program in Physical and Engineering Biology Yale University New Haven Connecticut 06520 USA Department of Physics Yale University New Haven Connecticut 06520 USA Department of Applied Physics Yale University New Haven Connecticut 06520 USA Department of Cell Biology Yale School of Medicine New Haven Connecticut 06520 USA Department of Molecular Cell and Developmental Biology Yale University New Haven Connecticut 06511 USA

Chromatin polymer dynamics are commonly described using the classical Rouse model. The subsequent discovery, however, of intermediate-scale chromatin organization known as topologically associating domains (TADs) in experimental Hi-C contact maps for chromosomes across the tree of life, together with the success of loop extrusion factor (LEF) model in explaining TAD formation, motivates efforts to understand the effect of loops and loop extrusion on chromatin dynamics. This paper seeks to fulfill this need by combining LEF-model simulations with extended Rouse-model polymer simulations to investigate the dynamics of chromatin with loops and dynamic loop extrusion. We show that loops significantly suppress the averaged mean-square displacement (MSD) of a gene locus, consistent with recent experiments that track fluorescently labeled chromatin loci. We also find that loops reduce the MSD's stretching exponent from the classical Rouse-model value of 1/2 to a loop-density-dependent value in the 0.45–0.40 range. Remarkably, stretching exponent values in this range have also been observed in recent experiments [Weber et al., Phys. Rev. Lett. 104, 238102 (2010); Bailey et al., Mol. Biol. cell 34, ar78 (2023)]. We also show that the dynamics of loop extrusion itself negligibly affects chromatin mobility. By studying static “rosette” loop configurations, we also demonstrate that chromatin MSDs and stretching exponents depend on the location of the locus in question relative to the position of the loops and on the local friction environment.

关键词： Chromatin Chromosomes DNA Polymers Brownian dynamics Langevin equation Rouse model

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Liver cell therapies:cellular sources and grafting strategies

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Frontiers of Medicine 2023年第3期17卷 432-457页

作者： Wencheng Zhang Yangyang Cui Yuan Du Yong Yang Ting Fang Fengfeng Lu Weixia Kong Canjun Xiao Jun Shi Lola M.Reid Zhiying He Institute for Regenerative Medicine Ji’an HospitalShanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200123China Shanghai Engineering Research Center of Stem Cells Translational Medicine Shanghai 200335China Shanghai Institute of Stem Cell Research and Clinical Translation Shanghai 200120China Postgraduate Training Base of Shanghai East Hospital Jinzhou Medical UniversityJinzhou 121001China The First Affiliated Hospital of Nanchang University Nanchang 330006China Graduate School of Frontier Biosciences Osaka UniversitySuitaOsaka565-0871Japan Department of General Surgery Ji’an HospitalShanghai East HospitalSchool of MedicineTongji UniversityJi’an 343006China Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology/UNC School of Medicine Chapel HillNC 27599USA

The liver has a complex cellular composition and a remarkable regenerative *** primary cell types in the liver are two parenchymal cell populations,hepatocytes and cholangiocytes,that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells,endothelia and various hemopoietic cell *** regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates,the extracellular matrix,working synergistically with soluble paracrine and systemic *** recent years,with the rapid development of genetic sequencing technologies,research on the liver’s cellular composition and its regulatory mechanisms during various conditions has been extensively *** breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases,offering potential solutions to the chronic shortage of livers and alternatives to liver *** review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and *** advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.

关键词： liver regeneration hepatocytes cholangiocytes stem cells organoids regulatory mechanisms transplantation/grafting strategies

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Biomimetic Strategies for Peripheral Nerve Injury Repair: An Exploration of Microarchitecture and cellularization

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Biomedical Materials and Devices 2023年第1期1卷 21-37页

作者： Perrelle, Jeremy M. Boreland, Andrew J. Gamboa, Jasmine M. Gowda, Prarthana Murthy, N. Sanjeeva Child Health Institute of New Jersey Rutgers Robert Wood Johnson Medical School New Brunswick NJ United States Department of Neuroscience and Cell Biology Rutgers Robert Wood Johnson Medical School New Brunswick NJ United States Graduate Program in Molecular Biosciences Rutgers University Piscataway NJ United States Laboratory for Biomaterials Research Department of Chemistry and Chemical Biology Rutgers University Piscataway 08854 NJ United States

Injuries to the nervous system present formidable challenges to scientists, clinicians, and patients. While regeneration within the central nervous system is minimal, peripheral nerves can regenerate, albeit with limitations. The regenerative mechanisms of the peripheral nervous system thus provide fertile ground for clinical and scientific advancement, and opportunities to learn fundamental lessons regarding nerve behavior in the context of regeneration, particularly the relationship of axons to their support cells and the extracellular matrix environment. However, few current interventions adequately address peripheral nerve injuries. This article aims to elucidate areas in which progress might be made toward developing better interventions, particularly using synthetic nerve grafts. The article first provides a thorough review of peripheral nerve anatomy, physiology, and the regenerative mechanisms that occur in response to injury. This is followed by a discussion of currently available interventions for peripheral nerve injuries. Promising biomaterial fabrication techniques which aim to recapitulate nerve architecture, along with approaches to enhancing these biomaterial scaffolds with growth factors and cellular components, are then described. The final section elucidates specific considerations when developing nerve grafts, including utilizing induced pluripotent stem cells, Schwann cells, nerve growth factors, and multilayered structures that mimic the architectures of the natural nerve. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s);author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

关键词： cellularized pathways Nerve guidance conduit Peripheral nerve regeneration Synthetic scaffolds

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Synthesis of Methotrexate-Loaded Dumbbell-Shaped Titanium Dioxide/Gold Nanorods Coated with Mesoporous Silica and Decorated with Upconversion Nanoparticles for Near-Infrared-Driven Trimodal Cancer Treatment

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ACS Applied Materials and Interfaces 2023年第28期15卷 33335-33347页

作者： Dash, Pranjyan Thirumurugan, Senthilkumar Tseng, Ching-Li Lin, Yu-Chien Chen, Sung-Lung Dhawan, Udesh Chung, Ren-Jei Taipei10608 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei110 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei110 Taiwan Research Center of Biomedical Device College of Biomedical Engineering Taipei Medical University Taipei110 Taiwan International Ph.D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei110 Taiwan Centre for the Cellular Microenvironment Division of Biomedical Engineering James Watt School of Engineering Mazumdar-Shaw Advanced Research Centre University of Glasgow GlasgowG116EW United Kingdom Taipei10608 Taiwan

This study prepared dumbbell-shaped titanium dioxide (TiO2)/gold nanorods (AuNRs) coated with mesoporous silica shells (mS) (AuNRs-TiO2@mS). Methotrexate (MTX) was further loaded into the AuNRs-TiO2@mS, and then upconversion nanoparticles (UCNPs) were decorated to form AuNRs-TiO2@mS-MTX: UCNP nanocomposites. TiO2 is used as an intense photosensitizer (PS) to produce cytotoxic reactive oxygen species (ROS), leading to photodynamic therapy (PDT). Concurrently, AuNRs exhibited intense photothermal therapy (PTT) effects and photothermal conversion efficiency. In vitro results suggested that these nanocomposites can kill oral cancer cells (HSC-3) without toxicity through irradiation of NIR laser, owing to the synergistic effect. The in vivo studies indicated that these nanocomposites exhibited excellent antitumor effects through synergistic PDT/PTT/chemotherapy under a near-infrared (NIR) 808 nm laser irradiation. Thus, these AuNRs-TiO2@mS: UCNP nanocomposites have great potential to undergo deep tissue penetration with enhanced synergistic effects through NIR-triggered light for cancer treatment. © 2023 American Chemical Society

关键词： Titanium dioxide

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In-Vitro Growth Kinetics of Mesenchymal Stem cells in Cytotoxicity Tests Using Low-Diluted Viscum Album

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Homeopathy 2022年第1期112卷 040-049页

作者： Ana Catarina Viana Valle Hilana dos Santos Sena Brunel Bruno Stéfano Lima Dallago Lucas Santana Rodrigues Patrícia Furtado Malard Rosiane Andrade da Costa Rafael Rossetto Rosângela Vieira de Andrade Doctor Izao Soares Institute Sao Paulo Brazil Graduate Program in Genomic Sciences and Biotechnology Catholic University of Brasilia Brazil BioInnova Brazil Brasilia University Brazil BioCell Cell Therapy Brazil

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Advances in AAV capsid engineering: Integrating rational design, directed evolution and machine learning

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Molecular Therapy 2025年第5期33卷 1937-1945页

作者： Nisanov, Alan M. Rivera de Jesús, Julio A. Schaffer, David V. Department of Chemistry University of California Berkeley Berkeley 94720 CA United States Department of Chemical and Biomolecular Engineering University of California Berkeley Berkeley 94720 CA United States Department of Bioengineering University of California Berkeley Berkeley 94720 CA United States Graduate Program in Bioengineering University of California Berkeley San Francisco and University of California Berkeley 94720 CA United States Department of Neurological Surgery University of California San Francisco 94143 CA United States Department of Molecular and Cell Biology University of California Berkeley Berkeley 94720 CA United States

Adeno-associated virus (AAV) has emerged as a highly promising vector for human gene therapy due to its favorable safety profile, versatility, and ability to transduce a wide range of tissues. However, natural AAV serotypes have shortcomings, including suboptimal transduction efficiency, pre-existing immunity, and a lack of tissue specificity, that hinder their therapeutic potential. To address these challenges, significant efforts are being applied to engineer novel AAV capsids. Rational design leverages structural insights to enhance capsid properties, directed evolution enables unbiased selection of superior variants, and machine learning accelerates discovery by computational analysis of high-throughput screening results to enable predictive algorithms. These strategies have yielded novel capsids with improved transduction efficiency, reduced immunogenicity, and enhanced tissue targeting. Future advances that continue to integrate such multi-disciplinary approaches will further drive the clinical translation of AAV-based therapies. © 2025 The Authors

关键词： AAV directed evolution gene therapy high-throughput screening machine learning next generation sequencing NGS rational design

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