Exendin-4 is a glucagon-like peptide-1 (GLP-1) receptor agonist and potent insulinotropic agent for type 2 diabetes patients; however, its therapeutic utility is limited due to the frequent ...injections required. Long-acting agonists reduce the number of injections, but they can compromise potency. In this study, chondroitin sulfate-g-glycocholic acid-coated and Exendin-4 (Ex-4)-loaded liposomes (EL-CSG) were prepared for oral administration of Ex-4. The Ex-4 loading efficiency was 77% and the loading content in the nanoparticles was 1 wt-%. In rat models, a single oral dose (200 μg/kg) of EL-CSG showed a relative oral bioavailability of 19.5%, compared with subcutaneous administration (20 μg/kg), and sustained pharmacokinetics for up to 72 h. The overall long-term pharmacodynamic effects, assessed by hemoglobin A1c (HbA1c), body weight, and blood lipid concentrations, of daily oral EL-CSG (300 μg/kg) for four weeks were equivalent to or better than daily subcutaneous injections of free Ex-4 solution (20 μg/kg).
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The maximally tolerated dose (MTD) approach in conventional chemotherapy accompanies adverse effects, primarily due to high drug concentrations in the blood after intravenous administration and ...non-specific damages to highly proliferating cells, including immune cells. This causes the immune system to dysfunction. To rather boost intrinsic tumor-fighting immune capacity, we demonstrate a new oral route treatment regimen of docetaxel (DTX) without apparent toxicity. The DTX-loaded cationic solid lipid nanoparticles (DSLN-CSG) were coated with an anionic polymer conjugated with glycocholic acid. The resulting nanoparticles (DSLN-CSG, ~120 nm in diameter) were actively absorbed in the distal ileum mediated by interactions with the apical sodium bile acid transporter. The plasma DTX profile was sustained up to 24 h after a single oral dose and did not impair the functions of the immune system. In mouse models, daily oral DSLN-CSG administration inhibited the growth of existing tumors and tumor formation by medication prior to cancer cell inoculation. The extent of effects depended on the cancer cell lines of melanoma, colorectal adenocarcinoma, and breast carcinoma. It was most effective for melanoma in growth inhibition and in preventing tumor formation in mice. During the medication, the cytotoxic T cell population increased while the populations of tumor-associated macrophage and regulatory T cell declined. The low dose daily oral treatment may help patients with intermittent maintenance therapy between MTD cycles and prevent tumor recurrence after completing remission for certain tumors.
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A broadband radar absorbing structure (RAS) covering both X and Ku bands (8.2–18.0 GHz) was designed by integrating an inductive frequency-selective carbon fiber fabric composite (FSFC) and ...multiwalled carbon nanotube (MWCNT)-loaded glass fabrics which can modulate EMI characteristics of the FSFC. All the layers of the structure consisted of fiber-reinforced fabrics, and thus general composite fabrication processes can be easily applied. An existing scaling law based on the percolation theory was modified to replicate permittivity of the MWCNT-loaded fabrics. Coefficients and exponents of the power law were expressed by frequency and MWCNT concentration. The modified model provides a good description of the dielectric property of MWCNT fabric composites, and thus paves the way for parametric evaluation of reflection loss of the FSFC-embedded double-layered RAS regarding the permittivity of the lossy dielectric composites, as well as thickness of each layer and the total thickness of the RAS. The reflection loss of the RAS, drawn from the parametric study, can cover 10 dB in the whole X and Ku bands with two separated absorption peaks, while its thickness was 3.63 mm only.
•3D-scanned plant models with different structural accuracies were analyzed.•Light interception of the models with a low accuracy were overestimated.•3D-scanned reconstruction can contribute to ...accurate analysis of photosynthesis.
Plant structure is a significant factor for influencing the light interception and photosynthesis of plants. The light interception on the plant surface can be analyzed by three-dimensional (3D) plant model and optical simulation, but its accuracy is directly affected by the structural accuracy of the 3D model. This study aims to analyze and compare the effect of the accuracy of 3D structural models on light interception and photosynthesis. 3D-scanned plant models with different structural accuracies were constructed, and the light interception and photosynthetic rate were analyzed at single leaf and whole-plant scales. When using a low accuracy model that lacked the fine structural details of the plant, it was overestimated in light interception and photosynthetic rate compared to the 3D-scanned model that has high structural accuracy. At the single leaf scale, the light interception was higher in the low-accuracy model than that in the 3D-scanned model due to self-shadings from higher curvature in the leaf surface. At the whole-plant scale, the light interception and the subsequent photosynthetic rate in the low-accuracy model were 18% and 45 to 58% higher than those in the 3D-scanned model at light intensities of 700–2000 μmol m−2 s−1 at the upper canopy. The 3D-scanned plant model could accurately estimate the light interception and photosynthetic rate of the plants through optical simulation. The presented methodology can contribute to accurate analyses of plant light environment, plant physiological response, and plant growth modelling.
In this paper, we propose a novel method realizing multi-input-multi-output (MIMO) transmission in near-field magnetic induction (NFMI) communication for increasing channel capacity where limited ...capacity is a major bottleneck problem in magnetic communication systems. Since conventional magnetic communication systems using the same antenna patterns cannot easily implement MIMO transmission due to strong crosstalk between transmitters, we propose heterogeneous antenna arrays with multipole antennas, enabling crosstalk cancellation. We confirm the crosstalk cancellation of the proposed antenna array through numerical simulations and experiments, and verify the capacity enhancement of the proposed NFMI communication system over conventional NFMI communication schemes.
Bile acid‐modified nanoparticles provide a convenient strategy to improve oral bioavailability of poorly permeable drugs by exploiting specific interactions with bile acid transporters. However, the ...underlying mechanisms are unknown, especially considering the different absorption sites of free bile acids (ileum) and digested fat molecules from bile acid‐emulsified fat droplets (duodenum). Here, glycocholic acid (GCA)‐conjugated polystyrene nanoparticles (GCPNs) are synthesized and their transport in Caco‐2 cell models is studied. GCA conjugation enhances the uptake by interactions with apical sodium‐dependent bile acid transporter (ASBT). A new pathway correlated with both ASBT and chylomicron pathways is identified. Meanwhile, the higher uptake of GCPNs does not lead to higher transcytosis to the same degree compared with unmodified nanoparticles (CPNs). The pharmacological and genomics study confirm that GCA conjugation changes the endocytosis mechanisms and downregulates the cellular response to the transport at gene levels, which works as a negative feedback loop and explains the higher cellular retention of GCPNs. These findings offer a solid foundation in the bile acid‐based nanomedicine design, with utilizing advantages of the ASBT‐mediated uptake, as well as inspiration to take comprehensive consideration of the cellular response with more developed technologies.
Glycocholic acid‐modification endows specific transcytosis pathways to carboxylated polystyrene nanoparticle (CPN) in Caco‐2 cells. The modified nanoparticle (GCPN) is internalized by apical sodium dependent bile acid transporter (ASBT) via unique endocytosis mechanisms and shared the pathway with chylomicron. The caco‐2 cells slow GCPN transcytosis rate by weakening the transport‐relevant pathways.
Docosahexaenoic acid (DHA) has been reported to induce tumor cell death by apoptosis. However, little is known about the effects of DHA on autophagy, another complex well-programmed process ...characterized by the sequestration of cytoplasmic material within autophagosomes. Here, we show that DHA increased both the level of microtubule-associated protein light-chain 3 and the number of autophagic vacuoles without impairing autophagic vesicle turnover, indicating that DHA induces not only apoptosis but also autophagy. We also observed that DHA-induced autophagy was accompanied by p53 loss. Inhibition of p53 increased DHA-induced autophagy and prevention of p53 degradation significantly led to the attenuation of DHA-induced autophagy, suggesting that DHA-induced autophagy is mediated by p53. Further experiments showed that the mechanism of DHA-induced autophagy associated with p53 attenuation involved an increase in the active form of AMP-activated protein kinase and a decrease in the activity of mammalian target of rapamycin. In addition, compelling evidence for the interplay between autophagy and apoptosis induced by DHA is supported by the findings that autophagy inhibition suppressed apoptosis and further autophagy induction enhanced apoptosis in response to DHA treatment. Overall, our results demonstrate that autophagy contributes to the cytotoxicity of DHA in cancer cells harboring wild-type p53.
To evaluate the features of the lamina cribrosa (LC) in pseudoexfoliation glaucoma (PXG) patients using enhanced depth imaging (EDI) of spectral-domain optical coherence tomography (SD OCT). The ...results were compared with those of patients with primary open-angle glaucoma (POAG).
Cross-sectional study.
Patients with PXG (n = 21) and POAG (n = 35) matched for age and visual field mean deviation (VF MD).
Participants were imaged using SD OCT. Lamina cribrosa thickness (LT) and anterior lamina cribrosa depth (ALD) were determined at 3 areas (mid superior, center, and mid inferior) by 2 examiners using an EDI mode of the optic nerve head.
The LT and ALD were compared between PXG and POAG eyes.
Mean ± standard deviation baseline untreated intraocular pressure was not significantly different between the 2 groups (PXG, 18.3 ± 8.2 mmHg; POAG, 15.3 ± 3.4 mmHg; P = 0.310). The mean VF MD was -12.7 ± 9.0 dB in the PXG group versus -11.6 ± 9.1 dB in the POAG group (P = 0.643). When compared with the POAG group, the PXG group demonstrated a significantly thinner LT in all 3 areas and a thinner mean LT (133.4 ± 14.5 μm in the POAG group vs. 121.3 ± 13.0 μm in the PXG group; P<0.001). Anterior lamina cribrosa depth did not demonstrate a significant difference in any of the 3 areas between both groups (mean ALD, 324.3 ± 91.9 μm in the POAG group vs. 358.7 ± 142.7 μm in the PXG group; P = 0.470). Of 21 eyes in the PXG group, 9 eyes demonstrated a unilateral clinical presentation. When we compared the PXG eyes and the apparently normal-looking fellow eyes of those 9 eyes, neither the LT nor ALD demonstrated a significant difference (P = 0.223 and P = 0.079, respectively).
Eyes with PXG demonstrate a thinner LC compared with POAG eyes at similar levels of glaucoma severity.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Accurate theragnosis of tumour is essential for improving the life rate of tumour patients. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used as both diagnostic and therapeutic ...agents. However, their application is often limited because of a lack of water solubility, lack of cancer treatment efficacy, and ineffective targeting of tumour cells. In this report, a double ligand (caffeic acid–polyethylene glycol–folic acid; FA–PEG–CA, caffeic acid–polyethylene glycol–pheophorbide-a; PheoA–PEG–CA) coated iron oxide nanoparticle has been fabricated that overcomes the limitations of conventional SPION. Photosensitizer and tumour targeting ligands were coated on SPION using a ligand-substitution method. We confirmed the successful substitution of oleic acid ligands with FA–PEG–CA and PheoA–PEG–CA ligands by FT-IR spectroscopy. The caffeic acid coated iron oxide nanoparticles (CAMNPs) also demonstrated high water solubility in an aqueous environment and folate-mediated active tumour targeting. The water solubility of CAMNPs was evaluated by DLS measurement and TEM images. The cytotoxicity of CAMNPs increased two-fold in MDA-MB-231 cells at a laser irradiation condition. The fabricated CAMNPs retained their ability to function as both MRI diagnostic and tumour-selective therapeutic agents. These results suggest that these efficient characteristics of CAMNPs can be incorporated into applications, thus enhancing the efficacy of clinical cancer treatment.
•Double ligand coated iron oxide nanoparticle has been fabricated.•High water solubility in an aqueous environment•Folate-mediated active tumour targeted iron oxide nanoparticles•MRI diagnostic and tumour-selective therapeutic agents
To compare the rate of change of circumpapillary retinal nerve fiber layer (cRNFL) thickness, macular volume and thickness, and optic nerve head (ONH) parameters assessed using spectral-domain ...optical coherence tomography (SD-OCT) between eyes with progressing and nonprogressing glaucoma.
Longitudinal, observational study.
Two hundred seventy-nine eyes from 162 glaucoma patients followed for an average of 2.2 years.
Eyes were classified as progressors and nonprogressors according to assessment of optic disc and RNFL photographs and visual field progression analysis. Linear mixed effects models were used to evaluate the overall rate of change of cRNFL thickness, macular volume and thickness, and ONH parameters after adjustment for age, spherical equivalent, signal strength, and baseline SD-OCT measurements.
The rate of change of cRNFL thickness, macular volume, and thickness and ONH parameters.
Sixty-three eyes (22.6%) from 52 subjects were identified as progressors. Average, inferior quadrant, and 6- and 7-o'clock sector cRNFL thickness decreased faster in progressors than in nonprogressors (-1.26 vs -0.94, -2.47 vs -1.75, -3.60 vs -2.52, and -2.77 vs -1.51 μm/year, respectively; all P<0.05). The ONH rim area decreased faster, and average and vertical cup-to-disc ratio increased faster in progressors than in nonprogressors (-0.016 vs -0.006 mm(2)/year, and 0.004 vs 0.002 and 0.006 vs 0.004 per year, respectively; all P<0.05). Macular cube volume and the thickness of temporal outer and inferior inner macular sectors decreased faster in progressors than in nonprogressors (-0.068 vs -0.048 mm(3)/year, and -2.27 vs -1.67 and -2.51 vs -1.73 μm/year, respectively; all P<0.05).
Serial measurement of parameters in all 3 areas (cRNFL, macula, and ONH) by SD-OCT may permit identification of progression in glaucomatous eyes.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
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