Quantitative Assessment of the Size-dependent Whole-body to Cellular Biodistribution of Fine Particulate Matters Following Inhalation by Fluorescence Imaging

Abstract Background: There has been growing concern regarding the impact of air pollution, especially fine dust, on human health. However, it is difficult to estimate the toxicity of fine dust on the human body because of its diverse effects depending on the composition and environmental factors.Results: In this study, we focused on the difference in the biodistribution of fine dust according to the size distribution of particulate matter after inhalation into the body to predict its impact on human health. We synthesized Cy7-doped silica particulate matters (CSPMs) having different particle sizes and employed them as model fine dust, and studied their whole-body in vivo biodistribution in BALB/c nude mice. Image-tracking and quantitative analysis were performed on the ex vivo organs and tissues. Additionally, flow cytometric analysis of single cells isolated from the lungs was performed. Smaller particles with a diameter of less than 100 nm (CSPM0.1) were observed to be removed relatively rapidly from the lungs upon initial inhalation. However, they were confirmed to accumulate continuously over 4 weeks of observation. In particular, smaller particles were found to spread rapidly to other organs during the early stages of inhalation.Conclusions: It is expected that the effect of fine dust on human health can be predicted through the differences in in vivo behavior that arise depending on the particle size. This study might provide with insights on association between CSPM0.1 accumulation in several organs including the lungs and adverse effect to underlying diseases in the organs.

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Two-Dimensional Modeling of Nanomechanical Strains in Healthy and Diseased Single-Cells During Microfluidic Stress Applications

Journal of Nanotechnology in Engineering and Medicine ◽

10.1115/1.4001309 ◽

2010 ◽

Vol 1 (2) ◽

Cited By ~ 9

Author(s):

Zachary D. Wilson ◽

Sean S. Kohles

Keyword(s):

Ex Vivo ◽

Single Cells ◽

Extensional Flow ◽

Molecular Engineering ◽

Creeping Flow ◽

Recent Analysis ◽

Two Dimensional ◽

Monitoring And Control ◽

The Impact

Investigations in cellular and molecular engineering have explored the impact of nanotechnology and the potential for monitoring and control of human diseases. In a recent analysis, the dynamic fluid-induced stresses were characterized during microfluidic applications of an instrument with nanometer and picoNewton resolution as developed for single-cell biomechanics (Kohles, S. S., Nève, N., Zimmerman, J. D., and Tretheway, D. C., 2009, “Stress Analysis of Microfluidic Environments Designed for Isolated Biological Cell Investigations,” ASME J. Biomech. Eng., 131(12), p. 121006). The results described the limited stress levels available in laminar, creeping-flow environments, as well as the qualitative cellular strain response to such stress applications. In this study, we present a two-dimensional computational model exploring the physical application of normal and shear stress profiles (with 0.1, 1.0, and 10.0 Pa peak amplitudes) potentially available within uniform and extensional flow states. The corresponding cellular strains and strain patterns were determined within cells modeled with healthy and diseased mechanical properties (5.0–0.1 kPa moduli, respectively). Strain energy density results integrated over the volume of the planar section indicated a strong mechanical sensitivity involving cells with disease-like properties. In addition, ex vivo microfluidic environments creating in vivo stress states would require freestream flow velocities of 2–7 mm/s. Knowledge of the nanomechanical stresses-strains necessary to illicit a biologic response in the cytoskeleton and cellular membrane will ultimately lead to refined mechanotransduction relationships.

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Peroxisome proliferator-activated receptor α deficiency modifies glucose handling by isolated mouse adipocytes

Journal of Endocrinology ◽

10.1677/joe-06-0205 ◽

2007 ◽

Vol 193 (1) ◽

pp. 39-43 ◽

Cited By ~ 10

Author(s):

C G Walker ◽

M C Sugden ◽

G F Gibbons ◽

M J Holness

Keyword(s):

Glucose Metabolism ◽

High Glucose ◽

Ex Vivo ◽

Whole Body ◽

Glucose Turnover ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Total Glucose ◽

The Impact

Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor that regulates enzymes involved in fatty acid (FA) utilisation. PPARα null mice have recently been demonstrated to have increased whole-body glucose turnover in vivo. This has been attributed to increased glucose uptake by adipose tissue, but the impact of PPARα deficiency on the characteristics of glucose handling by isolated adipocytes ex vivo is unknown. To determine directly the impact of PPARα deficiency on adipocyte glucose handling, thereby excluding any influence of humoral/neuronal factors, we examined total glucose metabolism as well as glucose disposition towards alternative fates in epididymal adipocytes isolated from wild-type and PPARαnull mice. Total glucose metabolism (oxidation, incorporation into FA and glycerol moieties of triglyceride (TAG) and conversion to lactate) was measured under basal conditions (low glucose) and ‘stimulated lipogenic’ conditions (high glucose + insulin). Adipocytes from PPARα null mice had higher rates of glucose metabolism under both basal and stimulated lipogenic conditions, with increased glucose utilisation both for oxidation and entry into the synthesis of the FA and glycerol components of lipid. In particular, the capacity of adipocytes from PPARα-deficient mice to utilise glucose for synthesis of the glycerol backbone of TAG was greatly enhanced under stimulated (high glucose + insulin) conditions. The increased use of glucose for the glycerol moiety of adipocyte TAG may therefore contribute to, and provide explanation for, enhanced glucose turnover in PPARα null mice.

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Synthesis of radioactively labelled CdSe/CdS/ZnS quantum dots for in vivo experiments

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.5.247 ◽

2014 ◽

Vol 5 ◽

pp. 2383-2387 ◽

Cited By ~ 1

Author(s):

Gordon M Stachowski ◽

Christoph Bauer ◽

Christian Waurisch ◽

Denise Bargheer ◽

Peter Nielsen ◽

...

Keyword(s):

Quantum Dots ◽

Phase Transfer ◽

Ex Vivo ◽

Biological Response ◽

Transport Processes ◽

The Body ◽

Whole Body ◽

Diagnostic Tools ◽

Colloidal Solutions

During the last decades of nanoparticles research, many nanomaterials have been developed for applications in the field of bio-labelling. For the visualization of transport processes in the body, organs and cells, luminescent quantum dots (QDs) make for highly useful diagnostic tools. However, intercellular routes, bio-distribution, metabolism during degradation or quantification of the excretion of nanoparticles, and the study of the biological response to the QDs themselves are areas which to date have not been fully investigated. In order to aid in addressing those issues, CdSe/CdS/ZnS QDs were radioactively labelled, which allows quantification of the QD concentration in the whole body or in ex vivo samples by γ-counting. However, the synthesis of radioactively labelled QDs is not trivial since the coating process must be completely adapted, and material availability, security and avoidance of radioactive waste must be considered. In this contribution, the coating of CdSe/CdS QDs with a radioactive 65ZnS shell using a modified, operator-safe, SILAR procedure is presented. Under UV illumination, no difference in the photoluminescence of the radioactive and non-radioactive CdSe/CdS/ZnS colloidal solutions was observed. Furthermore, a down-scaled synthesis for the production of very small batches of 5 nmol QDs without loss in the fluorescence quality was developed. Subsequently, the radio-labelled QDs were phase transferred by encapsulation into an amphiphilic polymer. γ-counting of the radioactivity provided confirmation of the successful labelling and phase transfer of the QDs.

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CellGPS: Whole-body tracking of single cells by positron emission tomography

10.1101/745224 ◽

2019 ◽

Author(s):

Kyung Oh Jung ◽

Tae Jin Kim ◽

Jung Ho Yu ◽

Siyeon Rhee ◽

Wei Zhao ◽

...

Keyword(s):

Positron Emission Tomography ◽

Single Cells ◽

The Body ◽

Emission Tomography ◽

Whole Body ◽

Cell Trafficking ◽

Anatomical Landmarks ◽

Average Cell ◽

Positron Emission

AbstractIn vivo molecular imaging tools are critically important for determining the role played by cell trafficking in biological processes and cellular therapies. However, existing tools measure average cell behavior and not the kinetics and migration routes of individual cells inside the body. Furthermore, efflux and non-specific accumulation of contrast agents are confounding factors, leading to inaccurate estimation of cell distribution in vivo. In view of these challenges, we report the development of a “cellular GPS” capable of tracking single cells inside living subjects with exquisite sensitivity. We use mesoporous silica nanoparticles (MSN) to concentrate 68Ga radioisotope into live cells and inject these cells into live mice. From the pattern of annihilation photons detected by positron emission tomography (PET), we infer, in real time, the position of individual cells with respect to anatomical landmarks derived from X-ray computed tomography (CT). To demonstrate this technique, a single human breast cancer cell was tracked in a mouse model of experimental metastasis. The cell arrested in the lungs 2-3 seconds after tail-vein injection. Its average velocity was estimated at around 50 mm/s, consistent with blood flow rate. Other cells were tracked after injection through other routes, but no motion was detected within 10 min of acquisition. Single-cell tracking could be applied to determine the kinetics of cell trafficking and arrest during the earliest phase of the metastatic cascade, the trafficking of immune cells during cancer immunotherapy, or the distribution of cells after transplantation in regenerative medicine.

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The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000116 ◽

2012 ◽

Vol 82 (3) ◽

pp. 228-232 ◽

Cited By ~ 7

Author(s):

Mauro Serafini ◽

Giuseppa Morabito

Keyword(s):

Antioxidant Capacity ◽

Dietary Intervention ◽

Ex Vivo ◽

The Body ◽

Dietary Polyphenols ◽

Enzymatic Antioxidant ◽

Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

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Histological, Biomechanical, and Biological Properties of Genipin-Crosslinked Decellularized Peripheral Nerves

International Journal of Molecular Sciences ◽

10.3390/ijms22020674 ◽

2021 ◽

Vol 22 (2) ◽

pp. 674

Author(s):

Óscar Darío García-García ◽

Marwa El Soury ◽

David González-Quevedo ◽

David Sánchez-Porras ◽

Jesús Chato-Astrain ◽

...

Keyword(s):

Ex Vivo ◽

Nerve Repair ◽

Wistar Rat ◽

Biomechanical Properties ◽

Biological Properties ◽

Suitable Alternative ◽

Promising Alternative ◽

Histological Pattern ◽

The Impact

Acellular nerve allografts (ANGs) represent a promising alternative in nerve repair. Our aim is to improve the structural and biomechanical properties of biocompatible Sondell (SD) and Roosens (RS) based ANGs using genipin (GP) as a crosslinker agent ex vivo. The impact of two concentrations of GP (0.10% and 0.25%) on Wistar rat sciatic nerve-derived ANGs was assessed at the histological, biomechanical, and biocompatibility levels. Histology confirmed the differences between SD and RS procedures, but not remarkable changes were induced by GP, which helped to preserve the nerve histological pattern. Tensile test revealed that GP enhanced the biomechanical properties of SD and RS ANGs, being the crosslinked RS ANGs more comparable to the native nerves used as control. The evaluation of the ANGs biocompatibility conducted with adipose-derived mesenchymal stem cells cultured within the ANGs confirmed a high degree of biocompatibility in all ANGs, especially in RS and RS-GP 0.10% ANGs. Finally, this study demonstrates that the use of GP could be an efficient alternative to improve the biomechanical properties of ANGs with a slight impact on the biocompatibility and histological pattern. For these reasons, we hypothesize that our novel crosslinked ANGs could be a suitable alternative for future in vivo preclinical studies.

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IMMU-31. QUANTITATIVE EVALUATION OF ROUTES OF ADMINISTRATION OF IMMUNOTHERAPEUTIC T CELLS TO ORTHOTOPIC GLIOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.461 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii111-ii111

Author(s):

Lan Hoang-Minh ◽

Angelie Rivera-Rodriguez ◽

Fernanda Pohl-Guimarães ◽

Seth Currlin ◽

Christina Von Roemeling ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Tumor Growth ◽

Ex Vivo ◽

Adoptive T Cell Therapy ◽

Whole Body ◽

T Cell Therapy ◽

Clinical Responses

Abstract SIGNIFICANCE Adoptive T cell therapy (ACT) has emerged as the most effective treatment against advanced malignant melanoma, eliciting remarkable objective clinical responses in up to 75% of patients with refractory metastatic disease, including within the central nervous system. Immunologic surrogate endpoints correlating with treatment outcome have been identified in these patients, with clinical responses being dependent on the migration of transferred T cells to sites of tumor growth. OBJECTIVE We investigated the biodistribution of intravenously or intraventricularly administered T cells in a murine model of glioblastoma at whole body, organ, and cellular levels. METHODS gp100-specific T cells were isolated from the spleens of pmel DsRed transgenic C57BL/6 mice and injected intravenously or intraventricularly, after in vitro expansion and activation, in murine KR158B-Luc-gp100 glioma-bearing mice. To determine transferred T cell spatial distribution, the brain, lymph nodes, heart, lungs, spleen, liver, and kidneys of mice were processed for 3D imaging using light-sheet and multiphoton imaging. ACT T cell quantification in various organs was performed ex vivo using flow cytometry, 2D optical imaging (IVIS), and magnetic particle imaging (MPI) after ferucarbotran nanoparticle transfection of T cells. T cell biodistribution was also assessed in vivo using MPI. RESULTS Following T cell intravenous injection, the spleen, liver, and lungs accounted for more than 90% of transferred T cells; the proportion of DsRed T cells in the brains was found to be very low, hovering below 1%. In contrast, most ACT T cells persisted in the tumor-bearing brains following intraventricular injections. ACT T cells mostly concentrated at the periphery of tumor masses and in proximity to blood vessels. CONCLUSIONS The success of ACT immunotherapy for brain tumors requires optimization of delivery route, dosing regimen, and enhancement of tumor-specific lymphocyte trafficking and effector functions to achieve maximal penetration and persistence at sites of invasive tumor growth.

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Ex Vivo Mitochondrial Respiration Parallels Biochemical Response to Ibrutinib in CLL Cells

Cancers ◽

10.3390/cancers13020354 ◽

2021 ◽

Vol 13 (2) ◽

pp. 354

Author(s):

Subir Roy Chowdhury ◽

Cheryl Peltier ◽

Sen Hou ◽

Amandeep Singh ◽

James B. Johnston ◽

...

Keyword(s):

Mitochondrial Respiration ◽

Ex Vivo ◽

Standard Dose ◽

Cell Receptor ◽

Lymphocytic Leukemia ◽

Clinical Tool ◽

Potential Biomarker ◽

Apoptotic Pathways ◽

The Impact

Mitochondrial respiration is becoming more commonly used as a preclinical tool and potential biomarker for chronic lymphocytic leukemia (CLL) and activated B-cell receptor (BCR) signaling. However, respiration parameters have not been evaluated with respect to dose of ibrutinib given in clinical practice or the effect of progression on ibrutinib treatment on respiration of CLL cells. We evaluated the impact of low and standard dose ibrutinib on CLL cells from patients treated in vivo on mitochondrial respiration using Oroboros oxygraph. Cytokines CCL3 and CCL4 were evaluated using the Mesoscale. Western blot analysis was used to evaluate the BCR and apoptotic pathways. We observed no difference in the mitochondrial respiration rates or levels of plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4), β-2 microglobulin (β-2 M) and lactate dehydrogenase (LDH) between low and standard doses of ibrutinib. This may confirm why clinical observations of the safety and efficacy of low dose ibrutinib are observed in practice. Of interest, we also observed that the mitochondrial respiration of CLL cells paralleled the increase in β-2 M and LDH at progression. Our study further supports mitochondrial respiration as a biomarker for response and progression on ibrutinib in CLL cells and a valuable pre-clinical tool.

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Computerized Tomography: A Perspective in the Pediatric Patient

PEDIATRICS ◽

10.1542/peds.59.2.305 ◽

1977 ◽

Vol 59 (2) ◽

pp. 305-308

Author(s):

Derek Harwood-Nash ◽

Herman Grossman ◽

Alvin Felman ◽

John Kirkpatrick ◽

Leonard Swischuk

Keyword(s):

Computerized Tomography ◽

Soft Tissues ◽

Conventional Radiography ◽

The United States ◽

The Body ◽

Whole Body ◽

Central Research ◽

X Ray ◽

Whole Body Ct

Computerized tomography (CT), a technique conceptualized by Oldendorf in 19611 and developed by Hounsfield2 of EMI-Tronics Inc. (EMI) Central Research Laboratories, has proven to be a successful innovation in neuroradiology. Reviews by Ambrose3 in England and by Baker et al.4 and by New et al.5 in the United States have clearly demonstrated the value of this new modality in neuroradiological diagnosis. In 1975 Houser et al.6 and Harwood-Nash et al.7 provided the initial clinical and radiological data about CT in infants and children. More recently this technique has been extended to the study of tissues and organs in the body other than those in the head. This has been accomplished by modification of the original machine into a whole-body CT system. Early reviews by Ledley et al.8 and by Alfidi et al.9 suggest a significant potential for diagnosis of lesions in the abdomen, pelvis, and thorax. The advantages of CT are that it is less invasive than standard special diagnostic radiological procedures and that for the first time it provides in vivo information regarding the content and the characteristics of tissue composing organs and masses. DESCRIPTION OF EQUIPMENT In conventional radiography an image is made on radiographic film by an attenuated X-ray beam. In passing through a core of tissue, each ray of the beam is attenuated as it is absorbed and scattered by the tissue in its path. The intensity of the transmitted ray depends on the sum total of X-ray attenuation by all the different soft tissues in its path.

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Alcohol Pattern Consumption Differently Affects the Efficiency of Macrophage Reverse Cholesterol Transport in Vivo

Nutrients ◽

10.3390/nu10121885 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1885

Author(s):

Daniela Greco ◽

Simone Battista ◽

Laura Mele ◽

Antonio Piemontese ◽

Bianca Papotti ◽

...

Keyword(s):

Reverse Cholesterol Transport ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

The Body ◽

Cholesterol Transport ◽

Drinking Patterns ◽

Cardiovascular Morbidity And Mortality ◽

Short Period ◽

The Impact

It has been well established that moderate alcohol consumption inversely correlates with cardiovascular morbidity and mortality, whereas binge alcohol drinking increases cardiovascular disease risk. The aim of this study was to assess in vivo the impact of different drinking patterns on reverse cholesterol transport (RCT); the atheroprotective process leading to the removal of excess cholesterol from the body. RCT was measured with a standardized, radioisotope-based technique in three groups of atherosclerosis-prone apolipoprotein E knock out mice: Placebo group, receiving water, which would mimic the abstainers; moderate group, receiving 0.8 g/kg alcohol/day for 28 days, which would mimic a moderate intake; binge group, receiving 0.8 g/kg alcohol/day for 5 days/week, followed by the administration of 2.8 g/kg alcohol/day for 2 days/week, which would mimic a heavy intake in a short period. Mice in the binge drinking group displayed an increase in total cholesterol, high density lipoprotein cholesterol (HDL-c) and non-HDL-c (all p < 0.0001 vs. placebo), and a significantly reduced elimination of fecal cholesterol. The moderate consumption did not lead to any changes in circulating lipids, but slightly improved cholesterol mobilization along the RCT pathway. Overall, our data confirm the importance of considering not only the total amount, but also the different consumption patterns to define the impact of alcohol on cardiovascular risk.

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