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Optical redox imaging of ANT1-de-cient muscles

Journal of Innovative Optical Health Sciences 2024年第1期17卷 135-140页

作者： He N.Xu Ryan M.Morrow Min Feng Huaqing Zhao Douglas Wallace Lin Z.Li britton chance laboratory of redox imaging Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Center for Mitochondrial and Epigenomic Medicine Children's Hospital of Philadelphia Research Institute Philadelphia PA 19104USA Center for Biostatistics and Epidemiology Lewis Katz School of Medicine at Temple University Philadelphia PA 19140USA

Adenine nucleotide translocator(ANT)is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner *** plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the *** isoform ANT1 predominately expresses in cardiac and skeletal *** or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular *** aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-de-cient *** and quadriceps resected from age-matched wild type(WT)and ANT1-de-cient mice were snap-frozen in liquid *** chance redox scanner was utilized to perform 3D optical redox *** sample underwent scanning across 3–5 *** averaging analysis showed no signi-cant differences in the redox indices(NADH,flavin adenine dinucleotide containing-flavoproteins Fp,and the redox ratio Fp/(NADH+Fp)between WT and ANT1-de-cient ***,quadriceps had higher Fp than hearts in both groups(p¼0:0004 and 0.01,respectively).Furthermore,the quadriceps were also more oxidized(a higher redox ratio)than hearts in WT group(p¼0:004).NADH levels were similar in all *** data suggest that under non-stressful physical condition,the ANT1-de-cient muscle cells were in the same mitochondrial state as WT ones and that the signi-cant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-de-cient *** imaging of muscles under physical stress can be conducted in future.

关键词： ANT1 redox ratio flavoproteins

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WORKING WITH AND LEARNING FROM BRIT

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Journal of Innovative Optical Health Sciences 2011年第4期4卷 479-482页

作者： LIN Z.LI Molecular imaging lab Department of Radiology Britton Chance Lab of Redox Imaging Eldridge Reeves Johnson Research Foundation Department of Biochemistry and Biophysics Perelman School of MedicineUniversity of Pennsylvania PhiladelphiaPA 19014USA

I had been closely working with *** chance from 2005-2010 on imaging mitochondrial redox state in cancer and stem cells.I had also learned much from him in daily work and personal *** I would like to share some of my memories and experiences including(1)Great science is not necessarily done with top-grade expensive instruments;(2)Brit was genuinely interested in and dedicated to science;(3)Brit's attention to detail and timely action;(4)Brit's open-mindedness;and(5)Brit being modest,appreciative,and caring for others.

关键词： britton chance mitochondria redox state cancer stem cell

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INTRODUCTION SPECIAL ISSUE IN MEMORY OF PROFESSOR britton chance

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Journal of Innovative Optical Health Sciences 2011年第3期4卷 I0001-I0003页

作者： Lin Z.Li Shoko Nioka Molecular imaging lab Department of Radiology britton chance lab of redox imaging Johnson Foundation Department of Biochemistry and Biophysics University of Pennsylvania

britton chance:One of the Most Outstanding Scientists in the World On June 3rd and 4th,2011,over 300 scientists and professionals from all over the world gathered at the Translational Research Center of the University of Pennsylvania to attend a memorial symposium on\britton chance:His Life,Times and Legacy"and a\Molecular Spectroscopy/imaging Workshop:from bench top to bedside"dedicated to britton chance as well.

关键词： Times chance symposium

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imaging redox STATE HETEROGENEITY WITHIN INDIVIDUAL EMBRYONIC STEM CELL COLONIES

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Journal of Innovative Optical Health Sciences 2011年第3期4卷 279-288页

作者： HE N.XU RUSSELL C.ADDIS DAVIDA F.GOINGS SHOKO NIOKA britton chance JOHN D.GEARHART LIN Z.LI Molecular imaging laboratory Department of Radiology University of PennsylvaniaSchool of Medicine PhiladelphiaPA 19104USA Institute for Regenerative Medicine and Department of Cell and Developmental Biology University of Pennsylvania School of Medicine PhiladelphiaPA 19104USA britton chance laboratory of redox imaging Johnson Research Foundation Department of Biochemistry and Biophysics University of Pennsylvania School of Medicine PhiladelphiaPA 19104USA Institute of Translational Medicine and Therapeutics University of Pennsylvania PhiladelphiaPA 19104USA

redox state mediates embryonic stem cell(ESC)differentiation and thus offers an important complementary approach to understanding the pluripotency of stem *** redox ratio(NADH/(Fp t NADH)),where NADH is the reduced form of nicotinamide adenine dinucleotide and Fp is the oxidizedflavoproteins,has been established as a sensitive indicator of mitochondrial redox *** this paper,we report our redox imaging data on the mitochondrial redox state of mouse ESC(mESC)colonies and the implications *** low-temperature NADH/Fp redox scanner was employed to image mESC colonies grown on a feeder layer of gamma-irradiated mouse embryonicfibroblasts(MEFs)on glass cover *** result showed significant heterogeneity in the mitochondrial redox state within individual mESC colonies(size:~200-440μm),exhibiting a core with a more reduced state than the *** more reduced state positively correlates with the expression pattern of Oct4,a well-established marker of *** observation is thefirst to show the heterogeneity in the mitochondrial redox state within a mESC colony,suggesting that mitochondrial redox state should be further investigated as a potential new biomarker for the stemness of embryonic stem cells.

关键词： redox imaging pluripotency NADH flavoproteins redox ratio

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MOF-derived La/ZnO–TiO2 composite with enhanced photocatalytic ability for degradation of tetracycline

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Progress in Natural Science:Materials International 2023年第4期33卷 544-550页

作者： Lin Zhang Jun Chen Lai-Bo Song Jun-Jie Pan Qing Luo School of Physical and Healthy Education Jiangxi Science and Technology Normal University School of Chemistry and Environmental Engineering Wuhan Institute of Technology britton chance Center for Biomedical Photonics at Wuhan National laboratory for Optoelectronics-Hubei Bioinformatics&Molecular imaging Key laboratory Department of Biomedical Engineering College of Life Science and Technology Huazhong University of Science and Technology Chemical Biology Center Lishui Institute of Agriculture and Forestry Sciences College of Materials Xiamen University

Developing effective and stable photocatalysts for organic pollutants degradation are still a big challenge in practical water treatment now. In this work, La doped ZnO–TiO2composite(La/ZnO–TiO2) were successfully fabricated by using PVP modified ZIF-8/TiO2as template via the absorption and pyrolysis routes. All as-fabricated materials were analyzed by XRD, SEM, TEM, BET, XPS, UV–vis absorption spectra and ESR spectra. PVP modified ZIF-8/TiO2was fully transferred into ZnO–TiO2after being pyrolyzed at high temperature under air *** doping of La can make ZnO–TiO2exhibiting red-shifted, which is attributed to the capture of photo-generated electrons by La, leading to the effective separation between photo-generated electrons and holes. Furthermore,the photocatalytic performance of all as-fabricated materials were explored by degradation of tetracycline(TC)solution under UV light irradiation. La/ZnO–TiO2exhibits excellent stability. And the photocatalytic degradation rate of La/ZnO–TiO2is 99.2%, which is even higher than ZnO(87.4%), ZnO–TiO2(87.4%), P25(TiO2)(92.7%).More than that, the effect of catalyst’s dose, effect of TC concentration and effect of pH for TC degradation have been well explored. The excellent photocatalytic performance of La/ZnO–TiO2makes it possible to be applied for degradation of organic pollutants in practice.

关键词： La/ZnO-TiO_2 Red-shifted Effective separation Photocatalytic performance Tetracycline

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Fluorescent and quantitative mitochondrial redox imaging of tumor targeted by Octa-RGD probe

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Journal of Innovative Optical Health Sciences 2016年第4期9卷 55-65页

作者： Shuang Sha Fei Yang Anle Wang Honglin Jin Zhihong Zhang Qiaoya Lin britton chance Center for Biomedical Photonics Wuhan National laboratory for Optoelectronics–Huazhong University of Science and Technology Wuhan 430074 P.R.China MoE Key laboratory for Biomedical Photonics Department of Biomedical Engineering Huazhong University of Science and Technology Wuhan 430074 P.R.China

Integrins,over-expressed in a broad range of cancer diseauses,are widely utilized as a tumor *** investigation also plays important roles in tumor ***-oping simple integrin-targetting probe and monitoring tumor metabolism will give opportunities to find ways for cancer treatment,however,the investigation of tumor metabolism with integrin receptor based probes has been rarely reported so ***,we developed an octavalent fuo-rescent probe *** by convenient genetic method,based on one tetrameric far-red fluo-rescent protein(fRFP)linked with RGD pept *** validated its inter gin targeting by confocal imaging in *** we screened a variety of tumor cells,and differentiated their binding affinity based on the fuorescence of the probe via flow *** these cells,CNE-2 cells had the highest uptake of the probe,while B16 cells had the lowest,corresponding with their intergin expression ***,the fuorescent and metabolic imaging was performed in HT1080(intergin postive)tumor,where nicotinamide adenine dinudeotide hydrogen(NADH),flavo-protein(Fp)and fRFP fuorescent signals were *** tumor from mice intravenously injected with Octa RGD probe displayed obviously higher NADH redox ratio NADH/(Fp+NADH)and fRFP signal,than those with fRFP *** suggested that integrin targeting may have influence on the target cell metabolism,and further demonstrated *** probe facilitated its uptake in the targeted tumor in *** paper developed a useful probe,which can bind integrins speci-cally and e±ciently in tumor cells,and together with tumor metabolic information,it may provide new insight for RGD targeting-based cancer therapeutics.

关键词： Integrin redox metabolism fRFP NADH Fp.

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KillerRed protein based in vivo photodynamic therapy and corresponding tumor metabolic imaging

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Journal of Innovative Optical Health Sciences 2016年第1期9卷 21-30页

作者： Qiaoya Lin Shuang Sha Fei Yang Honglin Jin Zhihong Zhang britton chance Center for Biomedical Photonics Wuhan National laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074 P.R.China MoE Key laboratory for Biomedical Photonics Department of Biomedical Engineering Huazhong University of Science and Technology Wuhan 430074 P.R.China

Photodynamic therapy(PDT)gains wide attention as a useful therapeutic method for *** is mediated by the oxygen and photosensitizer under the specific light irradiation to produce the reactive oxygen species(ROS),which induce cellular toxicity and regulate the redox potential in tumor ***,genetic photosensitizers of low toxicity and easy production are required to be ***,a unique red fluorescent protein exhibiting excellent phototoxic properties,has the potential to act as a photosensitizer in the application of tumor ***,the course of tumor redox metabolism during this treatment was rarely investigated so *** here,we investigated the effects of KillerRed-based PDT on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of nicotinamide adenine dinucleotide hydrogen(NADH)and flavoprotein(Fp),two important metabolic coenzymes of tumor *** showed the tumor growth had been significantly inhibited by KillerRedbased PDT treatment compared to control groups.A home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in *** Fp signal was elevated by nearly 4.5-fold,while the NADH signal decreased by 66%after light irradiation,indicating that Fp and NADH were oxidized in the course of KillerRedbased ***,we also observed correlation between the fluorescence distribution of KillerRed and *** suggests that the KillerRed protein based PDT might provide a new approach for tumor therapy accompanied by altering tumor metabolism.

关键词： Reactive oxygen species redox metabolism flavoprotein nicotinamide adenine dinucleotide hydrogen

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redox imaging OF THE p53-DEPENDENT MITOCHONDRIAL redox STATE IN COLON CANCER EX VIVO

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Journal of Innovative Optical Health Sciences 2013年第3期6卷 1-10页

作者： HE N.XU MIN FENG LILY MOON NATHAN DOLLOFF WAFIKEL-DEIRY LIN Z.LI Department of Radiology University of Pennsylvania PhiladelphiaPAUSA britton chance laboratory of redox imaging Johnson Research Foundation Department of Biochemistry and Biophysics Perelman School of Medicine University of Pennsylvania PhiladelphiaPAUSA Department of Medicine Penn State Hershey Medical Center and Penn State College of MedicineHersheyPAUSA Hematology/Oncology Penn State Hershey Medical Center HersheyPAUSA Abramson Cancer Center University of Pennsylvania PhiladelphiaPAUSA Institute of Translational Medicine and Therapeutics University of Pennsylvania PhiladelphiaPAUSA

The mitochondrial redox state and its heterogeneity of colon cancer at tissue level have not been previously *** has how p53 regulates mitochondial respi ration been measured at(deep)tissue level,presumably due to the unavailability of the technology that has sufficient spatial resolution and tissue penetration *** prior work demonstrated that the mito-chondrial redox state and its intnatumor heterogeneity is associated with cancer aggressiveness in human melanoma and breast cancer in mouse models,with the more metastatic tumons exhi-bit ing localized negions of more oxidized redox *** the chance redox scanner with an in-plane spatial resolution of 200 pm,we imaged the mitochondrial redox state of the wild-type p53 colon tumors(HCT116 p53 ut)and the p5-deleted colon tumors(HCT116 p53-/-)by cllcting the fuorescence si gnals of nicotinamide adenine dimucleotide(NA DH)and oxidized flavoproteins [Fp,including favin adenine dinucleotide(FAD)]from the mouse xenogmafts snap frozen at low *** results show that:(1)both tumor lines have significant degree of intratumor heterogeneity of the redox state,typically exhibiting a distinct bi modal distribution that either correlates with the spatial core-rim pattern or the“hot/oold”oxida tion-roduction patches;.(2)the p531-group is significantly more beterogencous in the mitochondrial redox state and has a more oxidized turmor core compared to the p53 wt group when the tunor sizes of the two groups are matched;(3)the tumor size dependence of the redox indices(such as Fp and Fp redox ratio)is significant in the p531-group with the larger ones being more oxidized and more hetero-geneous in their redox state,particularly more oxidized in the tumor central regions;(4)the H&E staining images of tumor soctions grossly correlate with the redox *** present work is the first to reveal at the submillimeter scale the intratumor heterogeneity pattem of the mitochon-drial redox state in colon cancer and

关键词： NADH favoprotein intratumor heterogeneity HCT116 p53 null necrotic

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基于NADH荧光的组织病理生理状态多参数在体监测与评价

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科学通报 2010年第25期55卷 2476-2486页

作者：施华 MAYEVSKY Avraham 华中科技大学武汉光电国家实验室(筹) Britton Chance生物医学光子学研究中心武汉430074

组织病理生理状态的实时多参数评价,无论在动物实验研究还是临床应用中均具有重要价值,一直是生命科学与医学研究者们广泛关注的热点.众所周知,临床手术过程或重症监护病房中,患者病理生理状态的实时监测是十分必需的.心、脑等重要组织... 详细信息

组织病理生理状态的实时多参数评价,无论在动物实验研究还是临床应用中均具有重要价值,一直是生命科学与医学研究者们广泛关注的热点.众所周知,临床手术过程或重症监护病房中,患者病理生理状态的实时监测是十分必需的.心、脑等重要组织脏器是否处于缺血缺氧等危急状态直接关系到病人的存活与否;早期发现术中和术后次要脏器的微循环障碍有助于提高器官移植等手术的成功率和降低术后并发症的发生率.临床常规使用的监测指标,如血压、心电、脉搏等,在生命指征的实时评价中发挥了重要作用.然而,目前的常规指标尚不足以从分子水平反映局部组织病理生理状态的早期改变.NADH是细胞线粒体中氧化还原呼吸链上的内源性关键分子,具有自发荧光性质,可作为一项灵敏的内源性含氧状态指标来反映机体的代谢状态和细胞活力.本文介绍了基于NADH自发荧光信号的细胞氧化还原状态在体监测方法,从分子水平预警机体的活力情况,结合微循环血流、血氧饱和度等多种生理参数的同步并行监测,不仅可在活体动物体内进行疾病的病理生理学机制研究和新药的药效评价,还有望应用于临床外科手术和重症监护病房,为机体活力和生命指征的实时监护提供分子水平的动态信息.目前,NADH荧光一维信号的获取技术发展最为成熟,可实现从离体、活细胞、活体动物乃至临床水平的实时动态监测,已处于临床推广应用阶段.二维动态成像也已经发展到活体动物实验阶段.三维成像由于受制于NADH荧光的穿透能力,只能在冷冻组织切片上实现.如何突破因高散射所致的荧光穿透能力受限的瓶颈,最大限度地减少环境因素对荧光信号的干扰,在分子水平实现组织病理生理状态的实时多参数评价,是生物医学光子学领域面临的巨大挑战.

关键词：病理生理氧化还原在体监测线粒体 NADH 自发荧光

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CHOP THER APY INDUCED MITOCHONDRIAL redox STATE ALTERATION IN NON-HODGKIN'S LYMPHOMA XENOGRAFTS

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Journal of Innovative Optical Health Sciences 2013年第2期6卷 29-35页

作者： H.N.XU H.ZHAO T.A.MIR S.C.LEE M.FENG R.CHOE J.D.GLICKSON L.Z.LI Department of Radiology University of Pennsylvania PhiladelphiaPAUSA britton chance laboratory of redox imaging Johnson Research Foundation Department of Biochemistry and Biophysics University of Pennsylvania PhiladelphiaPAUSA Biostatistics and Data Management Core The Children's Hospital of Philadelphia(CHOP) PhiladelphiaPAUSA Department of Biomedical Engineering University of Rochester RochesterNYUSA Abramson Cancer Center University of Pennsylvania PhiladelphiaPAUSA Institute of Translational Medicine and Therapeutics University of Pennsylvania PhiladelphiaPAUSA

We are interested in investigating whether cancer therapy may alter the mitochondrial redox state in cancer cells to inhibit their growth and *** redox state can be imaged by the redox scanner that collects the fuorescence signals from both the oxidized-fAavoproteins(Fp)and the reduced form of nicotinamide adenine dinucleotide(NADH)in snap frozen tissues and has been previously employed to study tumor aggressiveness and treatment ***,with the redox scanner we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large *** lymphoma cell line(DLCL2).The mice were treated with CHOP therapy,i.e,cyclophosphamide(C)+hydroxydoxorubicin(H)+Oncovin(O)+prednisone(P)with CHO administration on day 1 and prednisone administration on days *** Fp content of the treated group was significantly decreased(p=0.033)on day 5,and the mitochondrial redox state of the treated group was slightly more reduced than that of the control group(p=0.048).The decrease of the Fp heterogeneity(measured by the mean st andard deviation)had a border-line statistical significance(p=0.071).The result suggests that the mitochondrial metabolism of lymphoma cells was slightly suppressed and the lymphomas became less aggressive after the CHOP therapy.

关键词： NA DH flavoprotein DLCL2 therapeutic effect tumor metabolism

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