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Compared to the topically applied standard drug solutions, the drug-loaded contact lens showed significantly (p less then 0.05) greater corneal drug distribution after 24 h incubation. In vitro and in vivo antimicrobial activity of the MF loaded contact lens was superior to the standard drug solution. In vivo drug distribution studies showed greater tissue concentration of MF in cornea, sclera, and aqueous humor with contact lens application compared with drug solutions. Overall, the polymeric contact lens was efficient in delivering MF and DM at required therapeutic concentrations. The findings from the present study show that drug-eluting contact lenses could be used in post-operative conditions to prevent ocular infections.This study aims to design and characterize the layer-by-layer assembly of core-corona nanoarchitecture for novel surface-modified solid lipid nanoparticles. Oppositely charged β-cyclodextrin polymers were used to build corona structure onto lipid core, and the particle size, polydispersity index, and zeta potential of SLN with polymer layers were evaluated. Morphology of surface-modified SLN was identified using TEM. The effect of polymer coating on drug release pattern was investigated by in-vitro release studies. The biocompatibility of the novel SLN systems was assessed on various healty cell lines using in vitro cytotoxicity assay. The presence of the oppositely charged polymer layers was found to be effective on alteration of zeta potential from negative to positive values and an increased surface charge density was achieved in comparison to core SLN. The results also revealed that the drug release is mainly controlled by diffusion and β-cyclodextrin polymers could enhance the slow/controlled release of drug. Cytotoxicity assay results suggested that the novel, hierarchical core-corona structured SLNs don't have cytotoxic effects on healthy cells and can be safely used as drug carriers. Overall, the layer-by-layer assembly of β-cyclodextrin polymers is promising for designing surface-modified nanoarchitectures of lipid nanoparticles that may be applied via many administration routes.Green tea extract epigallocatechin-3-gallate (EGCG), as a kind of natural active compounds, has become a research hotspot in cancer treatment. However, poor stability, low bioavailability and antitumor efficacy limit the application of EGCG. In this study, mesoporous dopamine (MPDA) with high drug loading and good biocompatibility loaded EGCG, garlic extract diallyl trisulfide (DATS) and photosensitizer (indocyanine green, ICG) by π-π stacking and hydrophobic-hydrophobic interaction, and the nano-system involved filling the mesoporous of the MPDA with phase change material (1-tetradecanol, 1-TD) molecules, which acted as a thermosensitive gatekeeper. The results indicated that MPDA-ICG@TD has an excellent photothermal effect and good stability. Due to the solid-liquid phase transition characteristics of the phase change material, MPDA-ICG@TD could control the release of drugs under near-infrared laser irradiation. Besides, cytotoxicity and apoptosis experiments showed that MPDA-ICG/EGCG/DATS@TD could be efficiently inhibited 4T1 cell proliferation and accelerate cell apoptosis than use diallyl trisulfide or EGCG alone, which means that the combination of natural active compounds EGCG and diallyl trisulfide has excellent synergy and can effectively improve the antitumor effect of EGCG. Moreover, this nano-system exhibited non-toxicity and good blood compatibility. This study provides a promising and effective strategy for improving the antitumor efficacy of natural active compound EGCG.In plants, posttranscriptional gene silencing (PTGS) is induced by small RNAs (sRNAs) generated from various dsRNA precursors. To assess the impact of dsRNA origin, we compared downregulation of GFP expression triggered by inverted repeat (IR), antisense (AS) and unterminated sense (UT) transcripts transiently expressed from the estradiol-inducible promoter. VIT-2763 datasheet The use of homogeneously responding tobacco BY-2 cell lines allowed monitoring the onset of silencing and its reversibility. In this system, IR induced the strongest and fastest silencing accompanied by dense DNA methylation. At low induction, silencing in individual cells was binary (either strong or missing), suggesting that a certain threshold sRNA level had to be exceeded. The AS variant specifically showed a deviated sRNA-strand ratio shifted in favor of antisense orientation. In AS lines and weakly induced IR lines, only the silencer DNA was methylated, but the same target GFP sequence was not, showing that DNA methylation accompanying PTGS was influenced both by the level and origin of sRNAs, and possibly also by the epigenetic state of the locus. UT silencing appeared to be the least effective and resembled classical sense PTGS. The best responding UT lines behaved relatively heterogeneously possibly due to complexly arranged T-DNA insertions. Unlike IR and AS variants that fully restored GFP expression upon removal of the inducer, only partial reactivation was observed in some UT lines. Our results pointed out several not yet described phenomena and differences between the long-known silencer variants that may direct further research and affect selection of proper silencer variants for specific applications.Elastic and muscular arteries differ in structure, function, and mechanical properties, and may adapt differently to aging. We compared the descending thoracic aortas (TA) and the superficial femoral arteries (SFA) of 27 tissue donors (average 41±18 years, range 13-73 years) using planar biaxial testing, constitutive modeling, and bidirectional histology. Both TAs and SFAs increased in size with age, with the outer radius increasing more than the inner radius, but the TAs thickened 6-fold and widened 3-fold faster than the SFAs. The circumferential opening angle did not change in the TA, but increased 2.4-fold in the SFA. Young TAs were relatively isotropic, but the anisotropy increased with age due to longitudinal stiffening. SFAs were 51% more compliant longitudinally irrespective of age. Older TAs and SFAs were stiffer, but the SFA stiffened 5.6-fold faster circumferentially than the TA. Physiologic stresses decreased with age in both arteries, with greater changes occurring longitudinally. TAs had larger circumferential, but smaller longitudinal stresses than the SFAs, larger cardiac cycle stretch, 36% lower circumferential stiffness, and 8-fold more elastic energy available for pulsation.
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