scholarly journals Assessment of Polyethylene Glycol-Coated Gold Nanoparticle Toxicity and Inflammation In Vivo Using NF-κB Reporter Mice

2020 ◽  
Vol 21 (21) ◽  
pp. 8158
Author(s):  
Tzu-Yin Chen ◽  
Mei-Ru Chen ◽  
Shan-Wen Liu ◽  
Jin-Yan Lin ◽  
Ya-Ting Yang ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Hepatic Function ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Acute Injuries ◽  
Reporter Mice ◽  
Liver Health ◽  
Peg Coating

Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-κB transgenic reporter mice following intravenous injection of PEG-coated AuNPs. The results of different doses (1 and 4 μg AuNPs per gram of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-κB reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathological abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver; thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health.

Designed multifunctional polymeric nanomedicines: long-term biodistribution and tumour accumulation of aptamer-targeted nanomaterials

2018 ◽  
Vol 54 (82) ◽  
pp. 11538-11541 ◽  
Author(s):  
N. L. Fletcher ◽  
Z. H. Houston ◽  
J. D. Simpson ◽  
R. N. Veedu ◽  
K. J. Thurecht
Keyword(s):  
Polyethylene Glycol ◽  
Pet Imaging ◽  
Hyperbranched Polymer ◽  
Ex Vivo

We report a novel multifunctional hyperbranched polymer based on polyethylene glycol (PEG) as a nanomedicine platform that facilitates longitudinal and quantitative 89Zr-PET imaging, enhancing knowledge of nanomaterial biodistribution and pharmacokinetics/pharmacodynamics both in vivo and ex vivo.

The recalcification plasma clotting time. A valuable general clotting test in man and rats

1969 ◽  
Vol 47 (8) ◽  
pp. 689-693 ◽  
Author(s):  
Serge Renaud
Keyword(s):  
Platelet Count ◽  
Plastic Material ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Improved Method ◽  
Clotting Time ◽  
Vein Thrombosis ◽  
Hepatic Vein Thrombosis ◽  
Periodic Fluctuations

An improved method for determining the recalcification plasma clotting time (PCT) in siliconized and plastic material is described. Provided the plasma is stored at 29–30 °C, this general clotting test appears to give highly accurate and reproducible results. The PCT values were found to be related to the in vivo platelet count in rat, and to the total serum cholesterol and plasma fibrinogen in man. Serial determinations in two women indicated that the PCT was subject to periodic fluctuations connected with the menstrual cycle. Finally, it was observed that the clotting time of both platelet-rich and -poor plasma was inversely related to the severity of large hepatic vein thrombosis initiated by the injection of a S. typhosa endotoxin in hyperlipemic rats.

scholarly journals The hypocholesterolaemic effects ofLactobacillus acidophilusAmerican Type Culture Collection 4356 in rats are mediated by the down-regulation of Niemann-Pick C1-Like 1

2010 ◽  
Vol 104 (6) ◽  
pp. 807-812 ◽  
Author(s):  
Ying Huang ◽  
Jinfeng Wang ◽  
Yi Cheng ◽  
Yongchen Zheng
Keyword(s):  
Lactobacillus Acidophilus ◽  
Cholesterol Metabolism ◽  
Hdl Cholesterol ◽  
Culture Collection ◽  
Liver Cholesterol ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Down Regulation ◽  
Niemann Pick

The objective of the present study was to evaluate the effect ofLactobacillus acidophilus4356 on cholesterol metabolismin vivo.Rats were fed a cholesterol-enriched experimental diet with or withoutL. acidophilus4356 supplementation at a dose of 109 colony-forming units per d.L. acidophilus4356 feeding significantly lowered total serum cholesterol, LDL-cholesterol and TAG concentrations, but there was no change in the serum HDL-cholesterol concentrations. In addition, total liver cholesterol and TAG were decreased in theL. acidophilus4356-fed group. The expression of Niemann-Pick C1-Like 1 (NPC1L1) in the duodenum and jejunum was significantly decreased followingL. acidophilus4356 feeding.Lactobacillus acidophilus4356 increased the population of lactobacilli and bifidobacteria in the small intestine and faeces compared with the control. These results indicate that the probiotic potential of theL. acidophilus4356 strain in the control of cholesterol is at least partially mediated by the down-regulation ofNPC1L1. Furthermore, these results also potentially suggest a new mechanism that is responsible for the cholesterol-reducing effects of probiotics.

scholarly journals Understanding the Generation and Regulation of IL-4 Producing T Helper 2 Cells

2021 ◽  
Author(s):  
◽  
Helen Mearns
Keyword(s):  
Cell Activity ◽  
Physiological Role ◽  
Th2 Cells ◽  
Total Serum ◽  
T Helper ◽  
Th2 Response ◽  
Th2 Cell ◽  
Reporter Mice

<p>A keenly sought therapeutic approach for the treatment of allergic disease is the identification and neutralization of the cytokine that regulates the differentiation of Th2 cells. Th2 cells are CD4 T cells differentiated to secrete IL-4. These cells are exciting new targets for asthma therapies due to the key role they play in allergic airway diseases. Recently the cytokine IL-25 has been shown to enhance Th2 cell activity and play important roles in mediating allergic inflammatory responses. To investigate this further we crossed IL-25 deficient mice with GFP-IL-4 reporter mice and developed an assay of in vitro and in vivo IL-4 independent Th2 differentiation. These assays were used to determine whether IL-25 was critical for the formation of Th2 cells. We found there was no physiological role for IL-25 in either the differentiation of Th2 cells or their development to effector or memory Th2 subsets. In the strong Th2 setting of a helminth infection the absence of IL-25 resulted in no defects in the effector type 2 responses associated with T helper type 2 immunity including, mucous hyperplasia, class switching to IgE and protection against challenge infections. Importantly this data challenges the newly found and growing status of the cytokine IL-25 and its proposed role in promoting Th2 responses. The second part of this thesis investigated whether the genomic organisation, which reflects commitment to Th2 cytokine expression, could provide a clearer definition of a functional in vivo Th2 cell. Two distinct IL-4 reporter mice were crossed and Th2 in vivo assays were developed that allowed tracking of the individual alleles of IL-4 in a variety of tissue types and Th2 subsets. Interestingly in vivo expression of IL-4 is mostly monoallelic yet there is a small highly activated population of biallelic IL-4 expressing Th2 cells. Physiologically each allele of IL-4 was required for a functional Th2 response with total serum IgE titres up to 4 fold lower in IL-4+/- heterozygous compared to the IL-4+/+ sufficient animals and a significant loss in protective immunity against challenge infections with helminths occurred in the IL-4+/- heterozygous animals. The similarity in deficiencies in Th2 immunity in the IL-4+/- heterozygous and IL-4-/- deficient compared to the IL-4+/+ sufficient animals lead to the proposal that the generation of biallelic Th2 cells may be required for specialised cell-to-cell mediated delivery of tailored activation signals and higher quantities of IL-4 required to mediate fully developed Th2 immune responses.</p>

scholarly journals Prospective isolation of mouse and human hematopoietic stem cells using Plexin domain containing 2

2021 ◽  
Author(s):  
Yosuke Tanaka ◽  
Yasushi Kubota ◽  
Ivo Lieberam ◽  
Jillian L. Barlow ◽  
Josh W. Bramley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Fluorescent Protein ◽  
Imaging Techniques ◽  
Xenograft Model ◽  
Hematopoietic Stem ◽  
Reporter Mice ◽  
Green Fluorescent

AbstractNumerous strategies exist to isolate hematopoietic stem cells (HSCs) using complex combinations of markers and flow cytometry. However, robust identification of HSCs using imaging techniques is substantially more challenging which has prompted the recent development of HSC reporter mice. To date, none of the molecules used in these reporters have been useful for human HSC identification. Here we report that PLXDC2 is a useful marker for both mouse and human HSCs. Using a green fluorescent protein (GFP) knock-in at the Plxdc2 locus in mice (hereafter denoted as Plxdc2-GFP), we showed that Plxdc2-GFP is highly expressed in HSCs with 1 in 2.8 Plxdc2-GFP+CD150+ cells giving long-term multi-lineage reconstitution in transplantation. Moreover, we developed a novel human PLXDC2 antibody and showed that human PLXDC2+ HSCs have stronger long-term multilineage reconstitution ability compared with PLXDC2- HSCs in a xenograft model. Thus, our study identifies PLXDC2 as a highly relevant molecule in HSC identification, potentially allowing greater purity and live in vivo tracking of these cells.SummaryTo date, few molecules are available for isolation of HSCs across species. The present study shows that PLXDC2 is a highly useful molecule for isolation of HSCs, which works across mouse and human.

scholarly journals Increased response to cholesterol feeding in apolipoprotein C1-deficient mice

1995 ◽  
Vol 305 (3) ◽  
pp. 905-911 ◽  
Author(s):  
J H van Ree ◽  
M H Hofker ◽  
W J A A van den Broek ◽  
J M A van Deursen ◽  
H van der Boom ◽  
...  
Keyword(s):  
Serum Cholesterol ◽  
Embryonic Stem ◽  
Density Lipoprotein ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Low Density ◽  
Remnant Lipoproteins ◽  
Deficient Mice

The function of apolipoprotein (apo) C1 in vivo is not well understood. From in vitro studies it has been reported that an excess of apoC1 relative to apoE inhibits receptor-mediated uptake of remnant lipoproteins [Sehayek and Eisenberg (1991) J. Biol. Chem. 266, 22453-22459]. In order to gain a better understanding of the role of apoC1 in lipoprotein metabolism in vivo, we have generated apoC1-deficient mice by gene targeting in embryonic stem cells. Homozygous mutant mice are viable and do not show overt abnormalities. Serum triacylglycerol levels are increased by 60% on both a standard mouse diet and a mild hypercholesterolaemic diet compared with controls. Total serum cholesterol levels are similar to controls on the two diets. However, the level of high-density lipoprotein cholesterol in the apoC1-deficient mice fed on the mild hypercholesterolaemic diet is slightly decreased, which is accompanied by a 3-fold increase in very-low-density plus low-density lipoprotein (VLDL+LDL) cholesterol. On a severe atherogenic diet, the homozygous apoC1-deficient mice become hypercholesterolaemic, with a serum cholesterol level of 10.7 +/- 3.3 mM compared with 6.7 +/- 1.8 mM and 5.1 +/- 1.6 mM in heterozygous and control mice respectively. The increase in cholesterol is mainly confined to the VLDL+LDL-sized fractions. Binding experiments revealed that lipoproteins lacking apoC1 with d < 1.006 g/ml are poor competitors for 125I-labelled LDL binding to the LDL receptor on HepG2 cells. This suggests that total apoC1 deficiency leads to impaired receptor-mediated clearance of remnant lipoproteins rather than enhanced uptake, as was expected from data reported in the literature.

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