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A DOUBLE-MASKED, RANDOMIZED, SHAM-CONTROLLED, SINGLE-CENTER STUDY WITH PHOTOBIOMODULATION FOR THE TREATMENT OF DRY AGE-RELATED MACULAR DEGENERATION
摘要： The LIGHTSITE I study investigated the efficacy and safety of photobiomodulation (PBM) treatment in subjects with dry age-related macular degeneration. Thirty subjects (46 eyes) were treated with the Valeda Light Delivery System, wherein subjects underwent two series of treatments (3· per week for 3–4 weeks) over 1 year. Outcome measures included best-corrected visual acuity, contrast sensitivity, microperimetry, central drusen volume and drusen thickness, and quality of life assessments. Photobiomodulation-treated subjects showed a best-corrected visual acuity mean letter score gain of 4 letters immediately after each treatment series at Month 1 (M1) and Month 7 (M7). Approximately 50% of PBM-treated subjects showed improvement of $5 letters versus 13.6% in sham-treated subjects at M1. High responding subjects ($5-letter improvement) in the PBM-treated group showed a gain of 8 letters after initial treatment (P , 0.01) and exhibited earlier stages of age-related macular degeneration disease. Statistically significant improvements in contrast sensitivity, central drusen volume, central drusen thickness, and quality of life were observed (P , 0.05). No device-related adverse events were reported. Photobiomodulation treatment statistically improved clinical and anatomical outcomes with more robust benefits observed in subjects with earlier stages of dry age-related macular degeneration. Repeated PBM treatments are necessary to maintain benefits. These pilot findings support previous reports and suggest the utility of PBM as a safe and effective therapy in subjects with dry age-related macular degeneration.
关键词： contrast sensitivity,best-corrected visual acuity,light-emitting diode,vision loss,low-level light therapy,mitochondria,photobiomodulation,dry age-related macular degeneration,drusen
更新于2025-09-12 10:27:22
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Thulium Laser‐Assisted Versus Conventional Laparoscopic Partial Nephrectomy for the Small Renal Mass
摘要： Mitochondria-targeting cancer therapies have achieved unprecedented advances attributed to their superior ability for improving drug delivery efficiency and producing an enhanced therapeutic effect. Herein, we report a mitochondria-targeting camptothecin (CPT) polyprodrug system (MCPS) covalently decorated with a high-proportioned CPT content, which can realize drug release specifically responsive to a tumor microenvironment. The nonlinear structure of MCPS can form water-soluble unimolecular micelles with high micellar stability and improved drug accumulation in tumoral cells/tissues. Furthermore, a classical mitochondria-targeting agent, triphenylphosphonium bromide, was tethered in this prodrug system, which causes mitochondrial membrane potential depolarization and mediates the transport of CPT into mitochondria. The disulfide bond in MCPS can be cleaved by an intracellular reductant such as glutathione, leading to enhanced destruction of mitochondria DNA and cell apoptosis induced by a high level of reactive oxygen species. The systematic analyses both in vitro and in vivo indicated the excellent tumor inhibition effect and biosafety of MCPS, which is believed to be an advantageous nanoplatform for subcellular organelle-specific chemotherapy of cancer.
关键词： chemotherapy,reduction-activated,mitochondria-targeted,polyprodrug,cancer therapy
更新于2025-09-11 14:15:04
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[IEEE 2018 25th IEEE International Conference on Image Processing (ICIP) - Athens, Greece (2018.10.7-2018.10.10)] 2018 25th IEEE International Conference on Image Processing (ICIP) - Characterizing Robustness and Sensitivity of Convolutional Neural Networks in Segmentation of Fluorescence Microscopy Images
摘要： Convolutional neural networks (CNNs) recently have achieved remarkable success in segmentation of biological fluorescence microscopy images. Because many of these networks were developed initially for general computer vison tasks such as object detection and object recognition, it is necessary to characterize their performance to determine how they meet the needs of related biological studies. So far, performance characterization of such networks has focused primarily on segmentation accuracy. It remains unclear how different networks compare in their robustness in handling images of different conditions and their sensitivity in detecting subtle geometrical changes of biological structures. Here, we develop a method that uses realistic synthetic images to characterize the robustness and sensitivity of such networks. We use the method to compare the performance of two widely adopted CNNs: the fully convolutional network (FCN) and the U-Net, in segmentation of complex morphology of mitochondria. We also compare them against an adaptive active-mask algorithm in performance. We find that both networks outperform the adaptive active-mask algorithm in robustness and sensitivity and that U-Net outperforms FCN. Overall, our study provides new insights into the performance of CNNs in segmentation of fluorescence microscopy images.
关键词： Segmentation,robustness,sensitivity,convolutional neural networks,mitochondria
更新于2025-09-11 14:15:04
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Mitochondria-Targeting Identification of a Fluorescent Apoptosis-Triggering Molecule by Mass Spectrometry Unravels Drug Tracking
摘要： The real-time tracking of localization and dynamics of small molecules in organelles helps to understand their function and lock their potential targets at the subcellular resolution. To identify the mitochondria-targeting effect of small molecules (NA-17 and NA-2a) in cancer cells, we used mass spectrometry to study the distribution and enrichment of small molecules in mitochondria and the residual cytoplasm, which enables to trace action process of therapeutic molecules. Colocalization analysis with an image-guided way suggests that both NA-17 and NA-2a have mitochondria-targeting effect. However, Mass Spectrometry (MS) analysis reveals that only NA-2a has mitochondria-targeting and enrichment effect, whereas NA-17 only distributes in the residual cytoplasm. A combination of mitochondria imaging, immunoblotting, and MS analysis in mitochondria indicate that NA-17 neither have the ability to enter mitochondria directly nor possess mitochondria-targeting effect. Further studies reveal that NA-17 could not enter mitochondria even though mitochondrial permeability has changed after NA-17 treatment in cells, evident by the ROS generation and cytochrome C release. In the process of cellular metabolism, NA-17 itself is firmly locked in the cytoplasm during the metabolic process, and its metabolites containing fluorophores could enrich in mitochondria for cell-imaging. Our present studies furnish new insights into drug metabolism process.
关键词： small molecule,mitochondria-targeting,mass spectrometry,drug tracking
更新于2025-09-10 09:29:36
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Metabolic imaging with the use of?fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in?mouse oocytes
摘要： To determine whether metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) identifies metabolic differences between normal oocytes and those with metabolic dysfunction. Experimental study. Academic research laboratories. None. Oocytes from mice with global knockout of Clpp (caseinolytic peptidase P; n ? 52) were compared with wild-type (WT) oocytes (n ? 55) as a model of severe oocyte dysfunction. Oocytes from old mice (1 year old; n ? 29) were compared with oocytes from young mice (12 weeks old; n ? 35) as a model of mild oocyte dysfunction. FLIM was used to measure the naturally occurring nicotinamide adenine dinucleotide dehydrogenase (NADH) and flavin adenine dinucleotide (FAD) autofluorescence in individual oocytes. Eight metabolic parameters were obtained from each measurement (4 per fluorophore): short (t1) and long (t2) fluorescence lifetime, fluorescence intensity (I), and fraction of the molecule engaged with enzyme (F). Reactive oxygen species (ROS) levels and blastocyst development rates were measured to assess illumination safety. In Clpp-knockout oocytes compared with WT, FAD t1 and t2 were longer and I was higher, NADH t2 was longer, and F was lower. In old oocytes compared with young ones, FAD t1 was longer and I was lower, NADH t1 and t2 were shorter, and I and F were lower. FLIM did not affect ROS levels or blastocyst development rates. FLIM parameters exhibit strong differentiation between Clpp-knockout versus WT, and old versus young oocytes. FLIM could potentially be used as a noninvasive tool to assess mitochondrial function in oocytes.
关键词： Mitochondria,aging,mitochondrial unfolded protein response,fluorescence lifetime imaging microscopy,CLPP,FLIM,oocyte
更新于2025-09-10 09:29:36
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Multi-color live-cell super-resolution volume imaging with multi-angle interference microscopy
摘要： Imaging and tracking of near-surface three-dimensional volumetric nanoscale dynamic processes of live cells remains a challenging problem. In this paper, we propose a multi-color live-cell near-surface-volume super-resolution microscopy method that combines total internal reflection fluorescence structured illumination microscopy with multi-angle evanescent light illumination. We demonstrate that our approach of multi-angle interference microscopy is perfectly adapted to studying subcellular dynamics of mitochondria and microtubule architectures during cell migration.
关键词： super-resolution microscopy,live-cell imaging,multi-angle interference microscopy,mitochondria,microtubules
更新于2025-09-10 09:29:36
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A FRET-based ratiometric fluorescent probe for detection of intrinsically generated SO2 derivatives in Mitochondria
摘要： A mitochondria-targeted ratiometric fluorescent probe based on hemicyanine and pyrido[1,2-a]benzimidazole was presented. It shows high sensitivity and selectivity toward SO2 in pure water. The limit of detection (LOD) was as low as 26.7 nM, which is superior to most reported probes. Most importantly, the probe was successfully used for fluorescence imaging of endogenous bisulfite in mitochondria in Glioma cells.
关键词： pyrido[1,2-a]benzimidazole,water,cell imaging,hemicyanine,mitochondria
更新于2025-09-09 09:28:46
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A Two-Photon Ratiometric Probe for Hydrogen Polysulfide (H2Sn): Increase in Mitochondrial H2Sn Production in a Parkinson’s Disease Model
摘要： Hydrogen polysulfide (H2Sn, n>1), which is primarily generated during the crosstalk between H2S and reactive species (ROS and RNS), is receiving increasing attention in biochemical research. H2Sn is mostly generated in the mitochondria, and abnormal mitochondrial function and oxidative stress are directly related to many disorders including Parkinson's disease (PD). We now report a two-photon fluorescent probe (SPS-M1) for in situ detection of H2Sn and its application to a PD model to account the H2Sn levels. The probe exhibited selective and fast response to H2Sn along with a marked blue-to-green color change. SPS-M1 is sensitive enough to quantitative detection of endogenous H2Sn content in mitochondria using two-photon microscopy (TPM). Ratiometric TPM imaging of live neurons and brain slices using SPS-M1 revealed that H2Sn production is increased to a greater extent in the A53T α-synuclein (α-syn) overexpressing model than in the wild-type control. These findings suggest that the interactions of H2S and the increased ROS caused by α-syn overexpression may generate more H2Sn. By employing our recently published TP probe for mitochondrial H2S, we also found the relationship between the H2Sn and H2S; increased H2Sn and decreased H2S levels, indicating that H2S and H2Sn may play a significant role in the pathogenesis of PD. This result may be useful to biomedical studies, including PD.
关键词： two-photon microscopy,fluorescent probe,Parkinson’s disease,Hydrogen polysulfide,mitochondria
更新于2025-09-04 15:30:14
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Achieve Automated Organelle Biopsy on Small Single Cells Using a Cell Surgery Robotic System
摘要： Single cell surgery such as manipulation or removal of subcellular components or/and organelles from single cells is increasingly used for the study of diseases and their causes in precision medicine. This paper presents a robotic surgery system to achieve automated organelle biopsy of single cells with dimensions of less than 20 μm in diameter. The complexity of spatial detection of the organelle position is reduced by patterning the cells using a microfluidic chip device. A sliding mode nonlinear controller is developed to enable extraction of organelles, such as the mitochondria and the nucleus, from single cells with high precision. An image processing algorithm is also developed to automatically detect the position of the desired organelle. The effectiveness of the proposed robotic surgery system is demonstrated experimentally with automated extraction of mitochondria and nucleus from human acute promyelocytic leukemia cells and human fibroblast cells. Extraction is followed by biological tests to indicate the functionality of biopsied mitochondria as well as the cell viability after removal of mitochondria. The results presented here have revealed that the proposed approach of automated organelle biopsy on single small cells is feasible.
关键词： mitochondria,single cell manipulation,organelle biopsy,robotic surgery
更新于2025-09-04 15:30:14
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Real-time local oxygen measurements for high resolution cellular imaging
摘要： Single-cell metabolic investigations are hampered by the absence of flexible tools to measure local partial pressure of O2 (pO2) at high spatial-temporal resolution. To this end, we developed an optical sensor capable of measuring local pericellular pO2 for subcellular resolution measurements with confocal imaging while simultaneously carrying out electrophysiological and/or chemo-mechanical single cell experiments. Here we present the OxySplot optrode, a ratiometric fluorescent O2-micro-sensor created by adsorbing O2-sensitive and O2-insensitive fluorophores onto micro-particles of silica. To protect the OxySplot optrode from the components and reactants of liquid environment without compromising access to O2, the micro-particles are coated with an optically clear silicone polymer (PDMS, polydimethylsiloxane). The PDMS coated OxySplot micro-particles are used alone or in a thin (~50 micron) PDMS layer of arbitrary shape referred to as the OxyMat. Additional top coatings on the OxyMat (e.g., fibronectin, laminin, polylysine, special photoactivatable surfaces etc.) facilitate adherence of cells. The OxySplots report the cellular pO2 and micro-gradients of pO2 without disrupting the flow of extracellular solutions or interfering with patch-clamp pipettes, mechanical attachments, and micro-superfusion. Since OxySplots and a cell can be imaged and spatially resolved, calibrated changes of pO2 and intracellular events can be imaged simultaneously. In addition, the response-time (t0.5 = 0.7 s, 0 - 160 mm Hg) of OxySplots is ~100 times faster than amperometric Clark-type polarization microelectrodes. Two usage example of OxySplots with cardiomyocytes show (1) OxySplots measuring pericellular pO2 while tetramethylrhodamine methyl-ester (TMRM) was used to measure mitochondrial membrane potential (ΔΨm); and (2) OxySplots measuring pO2 during ischemia and reperfusion while rhod-2 was used to measure cytosolic [Ca2+]i levels simultaneously. The OxySplot/OxyMat optrode system provides an affordable and highly adaptable optical sensor system for monitoring pO2 with a diverse array of imaging systems, including high-speed, high-resolution confocal microscopes while physiological features are measured simultaneously.
关键词： Mitochondrial Calcium Uptake,Mitochondrial Calcium Uniporter,Mitochondria,Calcium,Calcium signaling in heart,oxygen optrode
更新于2025-09-04 15:30:14