Preparation, in vitro anti-tumour activity and in vivo pharmacokinetics of RGD-decorated liposomes loaded with shikonin.

Shikonin (SHK) has been evidenced to possess effects against various cancer cells. However, poor aqueous solubility and high toxicity restrict its application. In the study, RGD-decorated liposomes loaded with SHK (RGD-Lipo-SHK) were prepared via thin-film hydration method. Characterization and cellular uptake of liposomes was evaluated. Cytotoxicity of blank liposomes and different SHK formulations was measured against breast cancer cells (MDA-MB-231, MCF-7, and MCF-10A). Anti-tumour effects and pharmacokinetic parameters of different SHK formulations were appraised in tumour spheroids and in rat model, respectively. Liposomes displayed a particle size of less than 127 nm with a polydispersity index about 0.21. The encapsulation efficiency was about 91% for SHK, and drug leakage rate of liposomes was less than 6%. RGD-Lipo-SHK showed superior cellular internalization in the αvß3-positive MDA-MB-231 cells. Blank liposomes had no cytotoxicity to MDA-MB-231 and MCF-7 cells. Howbeit, different SHK formulations obviously inhibited proliferation of MCF-10A cells, especially free SHK. Meanwhile, RGD-Lipo-SHK significantly inhibited growth inhibition of tumour spheroids. The pharmacokinetics study indicated that the peak concentration, area under plasma concentration-time curves, half-life, and mean residence time of RGD-Lipo-SHK distinctly increased compared with those of free SHK. Altogether, these results demonstrated RGD-Lipo-SHK could reduce cytotoxicity, strengthen the antitumor-targeted effect, and prolong circulation time, which provides a foundation for further in vivo experimentations.

Strongly-adhesive easily-detachable carboxymethyl cellulose aerogel for noncompressible hemorrhage control.

Hemostats that can strongly adhere to wound tissue and are easy to remove when stopping bleeding are favored for the control of noncompressible hemorrhage. Here, we prepared a citric acid (CA)-crosslinked and N-hydroxysuccinimide (NHS) ester-activated carboxymethyl cellulose (CMC-NHS) aerogel for noncompressible hemostasis. CA was used to crosslink CMC to form a strengthened structure. NHS ester was introduced to activate the adhesion of CMC-NHS aerogel to wound tissue and promoted blood coagulation through the formation of amide crosslinks between CMC and erythrocytes and free blood proteins. The plentiful carboxyl groups could also trigger the intrinsic coagulation pathway. Thus, the aerogel could quickly adhere to wound tissue to stop bleeding, and then could be easily removed when fully hydrated as CMC was dissolved at the adhesion interface. The aerogel also had good biocompatibility and antibacterial capability. Overall, CMC-NHS aerogel is a competitive hemostat for the control of noncompressible hemorrhage.

Ferulic acid exerts Nrf2-dependent protection against prenatal lead exposure-induced cognitive impairment in offspring mice.

Prenatal and/or early postnatal exposure to lead (Pb) may be associated with deficits in cognitive function in the toddler offspring, and oxidative stress likely play a central role in mediating these adverse effects. Here, we tested the hypothesis that ameliorative effect of ferulic acid (FA) on lead-induced cognitive deficits attributed to its antioxidant properties in a nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent manner in the context of prenatal Pb exposure. To test this hypothesis, Nrf2 knockout and C57BL/6 wild type mouse dams were exposed/unexposed to PbAc (250 ppm) during gestation day 5 to postnatal day 14 via drinking water, and FA (50 mg/kg)/vehicle was administered orally to dams for 31 d. Spatial learning and memory in pups was assessed by Morris water maze. Biochemical assays, real-time PCR, western blot techniques were employed to evaluate oxidative stress and signaling pathways in the brain of pups. We report that lead acetate (PbAc) leads to deficits in cognitive functions in offspring, which were partially attenuated by FA (P<.05). In parallel, pretreatment with FA also significantly inhibited the PbAc-induced oxidative stress, as indicated by a change in NAD+/NADH ratio, glutathione (GSH) and malondialdehyde contents (all P<.05). Interestingly, FA significantly elevated the glutamate cysteine ligase and heme oxygenase 1 at levels of transcription and translation in both mice exposed and unexposed to Pb, increasing de novo synthesis of GSH (all P<.05). Furthermore, maternal FA administration activates extracellular signal-regulated kinases 1 and 2 and promotes more Nrf2 nuclear accumulation by increasing the Nrf2 total protein in brain of offspring mice (all P<.05). Conversely, FA failed to influence Pb-induced both memory deficits and oxidative stress in offspring of Nrf2 knockout mice (all P≥.05), suggesting that Nrf2 is essential in mediating the cognition-enhancing and antioxidant effects of FA. Overall, our results demonstrate that FA protects against Pb-induced offspring's cognitive deficits, suggesting that it is a promising candidate for the treatment of Pb toxicity.

Spectrophotometric determination of hydrogen peroxide in water by oxidative decolorization of azo dyes using Fenton system.

In this study, based on the oxidative decolorization of three azo dyes (Orange G (OG), Acid Orange 7 (AO7) and Reactive Black 5 (RB5)) with hydroxyl radicals generated in Fenton system, we have successfully established three types of azo dyes spectrophotometric methods for measuring aqueous hydrogen peroxide (H2O2) concentration. The decolorization extent of OG, AO7 and RB5 at the corresponding characteristic wavelengths of 478 nm, 484 nm and 597 nm are proportion to the concentration of H2O2 in aqueous solutions. Under the selected reaction conditions, three well linear correlations between the depletion of azo dyes and the H2O2 concentration are established in the range of 0.45-175 µmol L-1 of OG, 0.36-120 µmol L-1 of AO7 and 0.44-175 µmol L-1 of RB5, respectively. These proposed spectrophotometric methods are enough accurate to measure low concentrations of H2O2 in practical water samples and monitor the variations of H2O2 concentration during the phenol degradation in the Cu(II)/HCO3-/H2O2 process.

Astragaloside IV attenuates lead acetate-induced inhibition of neurite outgrowth through activation of Akt-dependent Nrf2 pathway in vitro.

Recently, oxidative stress is strongly associated with lead (Pb)-induced neurotoxicity. We reported previously that Astragaloside IV (AS-IV) possesses potent antioxidant properties. Here, we evaluate the hypothesis that AS-IV attenuates lead acetate (PbAc)-mediated inhibition of neurite outgrowth might mainly result from its antioxidant property via serine/threonine protein kinase (Akt)-dependent activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Interestingly, AS-IV attenuates PbAc-induced inhibition of neurite outgrowth and displayed potential antioxidant properties by inhibiting reactive oxygen species (ROS). Concomitantly, AS-IV enhanced phase II detoxifying enzymes such as heme oxygenase 1 (HO-1), thioredoxin reductase (TrxR), and glutamate cysteine ligase catalytic subunit (GCLc). Conversely, AS-IV had no effect on GCL modulatory subunit (GCLm) and superoxide dismutase (SOD) activity/expression. Furthermore, AS-IV evoked Akt phosphorylation, and subsequent induced phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) at Ser9 (that is, inactivation), which stimulated Nrf2-mediated antioxidant response element (ARE)-containing activation. Importantly, Akt locates upstream of GSK-3ß and regulates phase II detoxifying enzymes gene expression through Nrf2 nuclear accumulation in PC12 cells exposed to PbAc. Noteworthy, these results were further confirmed through signalling pathway inhibitors, dominant negative mutant and short hairpin RNA technology. Collectively, these in vitro findings suggest that AS-IV attenuates PbAc-induced inhibition of neurite outgrowth attributed to its antioxidant properties and may be a promising candidate for the treatment of lead developmental neurotoxicity.