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QUANTITATIVE REDOX SCANNING OF TISSUE SAMPLES USING A CALIBRATION PROCEDURE

Journal of Innovative Optical Health Sciences 2009年第4期2卷 375-385页

作者： HE N.XU BAOHUA WU SHOKO NIOKA BRITTON CHANCE LIN Z.LI Molecular Imaging Laboratory Department of Radiology University of PennsylvaniaPhiladelphia PA 19104USA johnson research foundation department of biochemistry and biophysics university of pennsylvania PA 19104USA

The fluorescence properties of reduced nicotinamide adenine dinucleotide(NADH)and oxidizedflavoproteins(Fp)including flavin adenine dinucleotide(FAD)in the respiratory chain are sensitive indicators of intracellular metabolic states and have been applied to the studies of mitochondrial function with energy-linked *** redox scanner,a three-dimensional(3D)low temperature imager previously developed by Chance et al.,measures the in vivo metabolicproperties of tissue samples by acquiring fluorescence images of NADH and *** redox ratios,***/(Fp+NADH)and NADH/(Fp+NADH),provided a sensitive index of the mitochondrialredox state and were determined based on relative signal intensity *** we report thefurther development of the redox scanning technique by using a calibration method to quantifythe nominal concentration of the fluorophores in *** redox scanner exhibited very goodlinear response in the range of NADH concentration between 165–1318µM and Fp between90–720µM using snap-frozen solution *** samples such as human tumor mousexenografts and various mouse organs were redox-scanned together with adjacent NADH and Fpstandards of known concentration at liquid nitrogen *** nominal NADH and Fpconcentrations as well as the redox ratios in the tissue samples were quantified by normalizing the tissue NADH and Fp fluorescence signal to that of the snap-frozen solution *** calibration procedure allows comparing redox images obtained at different time,independent of instrument *** quantitative multi-slice redox images revealed heterogeneity inmitochondrial redox state in the tissues.

关键词： NADH flavoprotein redox ratio mitochondria tissue heterogeneity

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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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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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MITOCHONDRIAL REDOX IMAGING FOR CANCER DIAGNOSTIC AND THERAPEUTIC STUDIES

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 325-341页

作者： LIN Z.LI HE N.XU MAHSA RANJI SHOKO NIOKA BRITTON CHANCE department of Radiology School of Medicine University of PennsylvaniaB6 Blockley Hall423 Guardian Drive PhiladelphiaPA 19104-6069USA The Institute for Translational Medicine and Therapeutics School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Biophotonics Laboratory department of Electrical Engineering and Computer Science university of Wisconsin-Milwaukee MilwaukeeWI 53211USA johnson research foundation department of biochemistry and Molecular biophysics School of Medicine University of Pennsylvania 250 Anatomy Chemistry BuildingPhiladelphiaPA 19104USA

Mitochondrial redox states provide important information about energy-linked biological processes and signaling events in tissues for various disease phenotypes including *** redox scanning method developed at the Chance laboratory about 30 years ago has allowed 3D highresolution(∼50×50×10µm^(3))imaging of mitochondrial redox state in tissue on the basis of the fluorescence of NADH(reduced nicotinamide adenine dinucleotide)and Fp(oxidized flavoproteins including flavin adenine dinucleotide,i.e.,FAD).In this review,we illustrate its basic principles,recent technical developments,and biomedical applications to cancer diagnostic and therapeutic studies in small animal *** developed calibration procedures for the redox imaging using reference standards allow quantification of nominal NADH and Fp concentrations,and the concentration-based redox ratios,e.g.,Fp/(Fp+NADH)and NADH/(Fp+NADH)in *** calibration facilitates the comparison of redox imaging results acquired for different metabolic states at different times and/or with different instrumental settings.A redox imager using a CCD detector has been developed to acquire 3D images faster and with a higher in-plane resolution down to 10µ*** vivo imaging and in vivo imaging of tissue mitochondrial redox status have been demonstrated with the CCD *** of tissue redox imaging in small animal cancer models include metabolic imaging of glioma and myc-induced mouse mammary tumors,predicting the metastatic potentials of human melanoma and breast cancer mouse xenografts,differentiating precancerous and normal tissues,and monitoring the tumor treatment response to photodynamic *** future directions for the development of redox imaging are also discussed.

关键词： Redox ratio reduced nicotinamide adenine dinucleotide NADH flavoprotein flavin adenine dinucleotide FAD calibration

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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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Citation analysis of the scientific publications of Britton Chance in ISI citation indexes

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Journal of Innovative Optical Health Sciences 2014年第2期7卷 129-142页

作者： Lin Z.Li Loet Leydesdorff Shoko Nioka Nannan Sun Eugene Garfield Departiment of Radiology PerelmanSchool of Medicine University of Penn.syluaninPhiladelphiaPA 19104USA Briton Chance Laboratory of Redoa Imaging Johnson Research FoundationDepartment of Biochemistryand BiophysicsPereiman School of Medicine University of Penn syluaniaPhiladelphiaPA 19104USA university of Amsterdam Amsterdam School of Communications research(ASCoR) Netherlands Briton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074P.R.China Inste for Scientific Informationo-Thomson Reuters Philadelphia PA 19180USA

Britton Chance was a pioneer in many scientifc fields such as enzymatic reaction kinetis,bioenergetics,metabolism,in vivo NMr,and *** an engineer,physical chemist,physicist,physiologist,biophysicist,biochemist,innovator and educator,he had worked indiversifed fields over extended periods bet ween 1926 until his death in 2010,at the age of *** to illustrate his scientific career and great impact on research from a new perspective,weemploy scientometric analysis tools to analyze the publications of Britton Chance with datadownloaded from the ISI Citation Indexes in April *** included articles,reviews andproceding papers but excluded meeting *** total,we obtained 1023 publication recordswith 1236 authors in 266 joumals with 17,114 citations from 1945 to *** show the annualpublications and citations that Britton Chance received from 1945 to 2013,and generate HistCitemaps on the basis of the global citations(GCS)and local(sel)citations(LCS)to show thecitation relationships among the top-30 publications of Britton *** and the development of physical methods to probe it appear to be the commecting thread of the lifelongresearch of Britton ***,we generate the joumal map and co-authorship maptoshow the broad scope of research topics and collaborators and the high impacts of the scientificoeuvre of Britton Chance ranging from physics,engineering,chemistry and biology to medicine.

关键词： Scientometric analysis impact Hist Cite citation tree metabolism mitochondria.

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3D imaging of the mitochondrial redox state of rathearts under normal and fasting conditions

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Journal of Innovative Optical Health Sciences 2014年第2期7卷 60-69页

作者： He N.Xu Rong Zhou Lily Moon Min Feng Lin Z.Li department of Radiology universityof PennsyluaniaPhilade lphia PA 19104USA Briton Chance Laboratory of Redor Imaging johnson research foundation Department of Biochemistry and Biophysics University of Pennsyluania Philade lphiaPA 19104USA Institute of Translational Medicine and Therapeutics Perelman School of Medicine university of pennsylvania Philadelphia PA 19104USA

The heart requires continuous ATP availability that is generated in the *** using the cell culture and perfiused organ models have been carried out to investigate thebiochemistry in the mitochondria in response to a change in substrate supply,mitochondrialbioenergetics of heart under normal feed or fasting conditions has not been studied at the tissuelevel with a sub-millimeter spatial resolution either in vivo or er *** of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD+couple acting as a central electron *** employed the Chance redox scanner thelow-temperat ure fluorescence scanner to image the three-dimensional(3D)spatial distribution of themitochondrial redox states in heart tissues of rats under normai feeding or an overnight star-vation for 14.5 *** consecutive sections of each heart were imaged to map three redoxindices,i.e,NADH,oxidized favoproteins Fp,including flavin adenine dinucleotide(FAD)andthe redox ratio NADH/*** imaging results revealed the micro-heterogeneity and the spatial distribution of these redox *** quantitative analysis showed that in the fasted hearts thestandard deviation of both NADH and Fp,ie.,SD NADH and SDFp,significantly decreasedwith a p value of 0.032 and 0.045,respectively,indicating that the hearts become relatively morehomogeneous after *** fasted hearts contained 28.6%less NADH(p=0.038).No *** change in Fp was foumnd(p=0.4).The NADH/Fp ratio decreased with a marginalP value(0.076).The decreased NADH im the fasted hearts is consistent with the cardiac celsreliance of fatty acids consumption for energy metabolism when glucose becomes *** o bservation of N ADH decrease induced by dietary restriction in the heart at tissuelevel has not been reported to our best *** Chance redox scanner demonstrated thefeasibility of 3D imaging of the mitochondrial redox st ate in the heart and

关键词： Mitochondion metabolism bioenergetics cardiomyocyte NADH flavoproteins Fp FAD caloric restriction food deprivation.

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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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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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Molecular landscapes of human hippocampal immature neurons across lifespan

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四川生理科学杂志 2022年第6期44卷 944-944页

作者： Yi Zhou department of Neuroscience and Mahoney Institute for Neurosciences Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of Neuroregeneration Nantong University Nantong China Institute for Regenerative Medicine University of Pennsylvania Philadelphia PA USA department of Cell and Developmental Biology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia PA USA The Epigenetics Institute Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Division of Neurosurgery Children’s Hospital of Philadelphia Philadelphia PA USA department of Neurosurgery Perelman School of Medicine University of Pennsylvania Philadelphia PA USA biochemistry and Molecular biophysics Graduate Group Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Neuroscience Graduate Group Perelman School of Medicine University of Pennsylvania Philadelphia PA USA department of Genetics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA department of Pathology and Laboratory Medicine Children’s Hospital of Philadelphia Philadelphia PA USA Division of Neurology Children’s Hospital of Philadelphia Philadelphia PA USA The Epilepsy NeuroGenetics Initiative (ENGIN) Children’s Hospital of Philadelphia Philadelphia PA USA department of Biomedical and Health Informatics (DBHi) Children’s Hospital of Philadelphia Philadelphia PA USA department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Lieber Institute for Brain Development The Solomon H. Snyder Department of Neuroscience Department of Neurology and Department of Psychiatry School of Medicine Johns Hopkins University Baltimore MD USA department of Pathology Johns Hopkins University School of Medic

Immature dentate granule cells(imGCs)arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological *** is known about... 详细信息

关键词： plasticity Molecular 1,2

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