-
Aguirre Moesgaard posted an update 6 months, 1 week ago
Furthermore, subcutaneous co-administration with MiNP allowed effector nanoparticles to achieve serum levels that rivaled a standard intravenous injection. This effect was only observed if the effector nanoparticles were injected within 24 h following MiNP administration, indicating a temporary avoidance of MPS cells. Co-injection with MiNP therefore allows reversible evasion of the MPS for targeted nanoparticles and presents a previously unexplored method of modulating and improving nanoparticle biodistribution following subcutaneous administration.Photodynamic therapy (PDT) is a promising noninvasive cancer treatment. PDT in the clinic faces several hurdles due to the unique tumor environment, a feature of which is high levels of glutathione (GSH). An excess amount of GSH consumes reactive oxygen species (ROS) generated by photosensitizers (PSs), reducing PDT efficiency. Herein, nano-photosensitizers (RuS1 NPs and RuS2 NPs) are reported. These consist of ruthenium complexes joined by disulfide bonds forming GSH sensitive polymer nanoparticles. The NPs achieve enhanced uptake compared to their constituent monomers. Inside cancer cells, high levels of GSH break the S-S bonds releasing PS molecules in the cell. The level of GSH is also then reduced leading to excellent PDT activity. Furthermore, RuS2 NPs functionalized with tumor targeting hyaluronic acid (HA@RuS2 NPs) assessed in vivo were highly effective with minimal side effects. To the best of our knowledge, RuS NPs are the first metal complex-based nano-assembled photosensitizers which exhibit enhanced specificity and consume endogenous GSH simultaneously, thus achieving excellent two-photon PDT efficiency in vitro and in vivo.There is currently a limited understanding of the effect of food structure on physical breakdown and gastric emptying of solid starch-based foods during gastric digestion. Moisture uptake, pH, particle size, rheological, and textural properties of six solid starch-based diets from different sources (Durum wheat and high amylose white rice) and of different macrostructures (porridge, native grain, agglomerate/couscous, and noodle) were monitored during 240 min of gastric digestion in a growing pig model. Changes in the physical properties of the gastric digesta were attributed to the influence of gastric secretions and gastric emptying, which were both dependent on the buffering capacity and initial macrostructure of the diets. Differences between the proximal and distal stomach regions were found in the intragastric pH and texture of the gastric digesta. For example, rice couscous, which had the smallest particle size and highest buffering capacity among the rice-based diets, had the shortest gastric emptying half-time and no significant differences between proximal and distal stomach digesta physical properties. Additionally, a relationship between gastric breakdown rate, expressed as gastric softening half-time from texture analysis, and gastric emptying half-time of dry matter was also observed. These findings provide new insights into the breakdown processes of starch-based solid foods in the stomach, which can be beneficial for the development of food structures with controlled rates of breakdown and gastric emptying during digestion.Plant cell imaging is critical for agricultural production and plant pathology study. Advanced upconversion nanoparticles (UCNPs) are being developed as fluorescent probes for imaging cells and tissues in vivo and in vitro. mTOR inhibitor Unfortunately, the thick cellulosic walls as barriers together with hemicelluloses and pectin hinder the entrance of macromolecules into the epidermal plant cell. Hence, realizing satisfactory temporal and spatial resolution with UCNPs remains an arduous task. Here, bipyramidal LiErF41%Tm3+@LiYF4 core-shell UCNPs with a super-bright red emission upon 980 nm laser excitation are explored, where the introduction of Tm3+ ions permits alleviation of the energy loss at defective sites and a significant improvement of the upconversion output. The as-obtained bipyramidal UCNPs could readily puncture plant cell walls and further penetrate into cell membranes, facilitating improved tissue imaging of cellular internalization, as demonstrated with the luminescence images obtained by multiphoton laser-scanning microscopy. Hence our work opens up a new avenue for exploring effective upconversion nanoparticles for achieving high resolution imaging of plant tissues.Breast cancer (BC) is a heterogeneous disease distinct from major clinical hindrances, and microRNAs (miRNAs) have been accounted to partake in BC progression. Identifying potential miRNAs and their pathological significance in BC could pave the way for precisely targeted treatments. This study exploits transcriptomic BC miRNA, mRNA cohorts, and prognostic significance via an integrative functional approach. miRNA transcriptomic cohorts (GSE45666, GSE40267, and GSE19783) were utilized to disseminate differentially expressed miRNAs (DEmiRNAs) and their expression in the clinicopathological variables of BC. miR-182 was identified as a potent candidate, differentially expressed between each BC stage and its adjacent normal samples. The expression of miR-182 was significantly associated with estrogen receptor (ER) (p = 0.052), and closely related to progesterone receptor (PR) (p = 0.061) and human epidermal growth factor receptor 2 (Her2) (p = 0.077). miRNA-mRNA regulatory targets were predicted using six different databases, namely, TargetScan, miRDB, Diana, miRNet, TargetMiner, and miRWalk. Twenty-four promising mRNA regulatory targets were potentially identified for miR-182 and thus highly enriched with cellular metabolic processes, proteoglycans, and focal adhesion pathways in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Subsequently, the F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) gene was recognized as a hub with the highest connectivity score in the protein-protein interaction network. Furthermore, miR-182 and FBXW7 were associated with poor prognostic clinical outcomes in BC patients. Thus, our integrated functional analysis suggests that miR-182 might lead to a new therapeutic target in BC manifestation.