Int J Med Sci
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Background: Combination chemotherapy plays an important role in the clinical therapy of non-small cell lung cancer (NSCLC). However, the pharmacokinetic differences between drugs are an insurmountable barrier in traditional treatment. For the synergistic therapy of NSCLC, synergistic nanoparticles (EDS NPs) loaded with both an EGFR inhibitor and doxorubicin (DOX) were designed and prepared. ⋯ The in vivo distribution showed that EDS NPs could enhance accumulation in tumors and decrease nonspecific accumulation in normal organs. EDS NPs significantly promoted the in vivo synergistic effects of icotinib and DOX in the mouse model. Conclusions: The study suggests that EDS NPs possess noteworthy potential for development as therapeutics for NSCLC clinical chemotherapy.
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Impacted third molars are commonly seen in teenagers and young adults and can cause considerable suffering. Preventing eruption of the third molars can reduce pain at the source. Our previous study has shown that dexamethasone (DEX) at a certain concentration can prevent the eruption of third molars without damaging alveolar bone in Sprague-Dawley (SD) rats, but the relevant molecular mechanisms need to be explored. ⋯ Further investigation revealed that overexpression of BMP7 attenuated the DEX-mediated inhibition of AKT and GSK-3β phosphorylation, but knockdown of BMP7 exerted the opposite effects. This study suggests that high concentrations of DEX may inhibit the expression of β-catenin via the PI3K/AKT/GSK-3β pathway in a manner mediated by BMP7. The findings further illustrate the possible molecular mechanisms by which DEX prevents tooth development.
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Abnormal angiogenesis is one of the significant features in periodontitis leading to progressive inflammation, but angiogenic changes of periodontal ligaments under inflammatory condition were rarely reported. Periodontal ligament stem cells (PDLSCs) were a kind of dental stem cells associated with vascularization. Here we investigated the alteration of angiogenesis of periodontal ligament in periodontitis, and revealed an exosome-mediated pathway to support the effect of PDLSCs on angiogenic improvement. ⋯ Inflammation inhibited miR-17-5p expression of PDLSCs and relieved its target VEGFA. However, overexpression of miR-17-5p blocked the pro-angiogenic ability of inflamed PDLSCs. In conclusion, the findings indicated that vascularization of periodontal ligaments was enhanced, and inflammatory micro-environment of periodontitis facilitated pro-angiogenesis of PDLSCs through regulating exosome-mediated transfer of VEGFA, which was targeted by miR-17-5p.
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The filamentous actin (F-actin) cytoskeleton is progressively damaged after status epilepticus (SE), which is related to delayed neuronal death, aberrant recurrent circuits and epileptogenesis. Glucocorticoids regulate dendritic spine remodeling by acting on glucocorticoid receptors and the dynamics of the F-actin cytoskeleton. Our previous study showed that administration of dexamethasone (DEX) in the latent period of the pilocarpine epileptic model reduces damage to the hippocampal filamentous actin cytoskeleton and the loss of hippocampal neurons and aids in maintaining the synaptic structures, but it is not sufficient to stop epileptogenesis. ⋯ We found that the latency of Stage 3 seizures increased, the mortality decreased, the damage to the synaptic F-actin cytoskeleton in the hippocampal subfields was significantly attenuated, and a greater number of postsynaptic structures were retained in the hippocampal subfields after treatment with DEX. These results indicate that treatment with dexamethasone stabilizes the synaptic F-actin cytoskeleton and reduces the damage to the brain due to SE. This approach is expected to be beneficial in alleviating delayed neuron damage and the process of epileptogenesis.
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Confocal Raman microspectral imaging was adopted to elucidate the cellular drug responses of osteosarcoma cells (OC) to N-[N-(3, 5-difluorophenyl acetyl)-L-alanyl]-sphenylglycine butyl ester (DAPT), a γ-secretase inhibitor, by identifying the drug induced subcellular compositional and structural changes. Methods: Spectral information were acquired from cultured osteosarcoma cells treated with 0 (Untreated Group, UT), 10 (10 μM DAPT treated, 10T), 20 μM (20 μM DAPT treated, 20T) DAPT for 24 hours. A one-way ANOVA and Tukey's honest significant difference (HSD) post hoc multiple test were sequentially applied to address spectral features among three groups. ⋯ In an addition, DAPT-induced nuclear fragmentation and apoptosis was depicted by the univariate Raman image of major cellular components (nucleic acids, proteins and lipids). Conclusions: The achieved Raman spectral and imaging results illustrated detailed DAPT-induced subcellular compositional and structural variations as a function of drug dose. Such observations can not only explain drug therapeutic mechanisms of OC DAPT treatment, and also provide new insights for accessing the medicine curative efficacy and predicting prognosis.