pH and redox dual stimulate-responsive nanocarriers based on hyaluronic acid coated mesoporous silica for targeted drug delivery.

In this work, we developed a drug-conjugated nanocarrier with "zero premature release" property for actively targeted drug delivery. The pH and redox dual-responsive nanocarrier was fabricated based on hyaluronic acid (HA) modified the mesoporous silica nanoparticles (MSNs). Doxorubicin (DOX) was conjugated to MSNs via hydrazone bonds, which can be cleaved in tumor tissue (acidic conditions). To improve specific cellular uptake and stability of nanocarriers, HA was equipped with an outer shell on the nanoparticle surface via a disulfide crosslinker. Stimulus-induced release of the DOX was studied in the different pH and GSH, which showed the embedded DOX can be controlled release from MSN channels. The dual-triggered drug release system provides an efficient targeted drug delivery system into the cytosol of cancer cells. The results of flow cytometry and confocal laser scanning microscopy (CLSM) showed that the HA-functionalized DOX-conjugated nanoparticles presented much better cellular uptake and higher cytotoxicity to tumor cells. This drug delivery system has great potential for tumor-trigged drug release for cancer therapy.

Redox-responsive nanocarriers for drug and gene co-delivery based on chitosan derivatives modified mesoporous silica nanoparticles.

Stimuli-responsive nanocarriers for anticancer drug and gene co-delivery are promising strategy in cancer therapy. The ultimate goal is to deliver high local concentration of therapeutic agents with no premature release and result in synergistic effects for combination therapies. In this work, we developed a redox stimuli-responsive and synergistic co-delivery system for anticancer drug DOX and p53 gene for potential cancer therapy. A dendronized chitosan derivative (CP) as a "gatekeeper" to control release the drug was used to modify MSNs via a disulfide linker and improve the gene transfection efficiency. Stimulus-induced release of the DOX was studied in the presence of glutathione (GSH), which showed that polymer shell was shed and accelerated the release of embedded drugs inside the tumor cells under a GSH-rich environment. The obtained nanoparticles showed good gene delivery ability in vitro by inducing an obvious increase in p53 protein expression in Hela cells. Apoptosis analysis confirmed that DOX and p53 could be co-delivered to the Hela cells by MSN-SS-CP nanocarriers and induced significant cell apoptosis. These results demonstrated that the dual delivery system resulted in synergistic effects and lead to an effective cancer cell apoptosis, which may be promising for cancer therapeutic application.

Stearic acid protects primary cultured cortical neurons against oxidative stress.

AIM: To observe the effects of stearic acid against oxidative stress in primary cultured cortical neurons. METHODS: Cortical neurons were exposed to glutamate, hydrogen peroxide (H2O2), or NaN3 insult in the presence or absence of stearic acid. Cell viability of cortical neurons was determined by MTT assay and LDH release. Endogenous antioxidant enzymes activity[superoxide dismutases (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)] and lipid peroxidation in cultured cortical neurons were evaluated using commercial kits. {3-[1(p-chlorobenzyl)- 5-(isopropyl)-3-t-butylthiondol-2-yl]-2,2-dimethylpropanoic acid, Na} [MK886; 5 micromol/L; a noncompetitive inhibitor of proliferator-activated receptor (PPAR) alpha], bisphenol A diglycidyl ether (BADGE; 100 micromol/L; an antagonist of PPAR gamma), and cycloheximide (CHX; 30 micromol/L, an inhibitor of protein synthesis) were tested for their effects on the neuroprotection afforded by stearic acid. Western blotting was used to determine the PPAR gamma protein level in cortical neurons. RESULTS: Stearic acid dose-dependently protected cortical neurons against glutamate or H2O2 injury and increased glutamate uptake in cultured neurons. This protection was concomitant to the inhibition of lipid peroxidation and to the promotion activity of Cu/Zn SOD and CAT in cultured cortical neurons. Its neuroprotective effects were completely blocked by BADGE and CHX. After incubation with H2O2 for 24 h, the expression of the PPAR gamma protein decreased significantly (P<0.05), and the inhibitory effect of H2O2 on the expression of PPAR gamma can be attenuated by stearic acid. CONCLUSION: Stearic acid can protect cortical neurons against oxidative stress by boosting the internal antioxidant enzymes. Its neuroprotective effect may be mainly mediated by the activation of PPAR gamma and new protein synthesis in cortical neurons.

Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices.

Arachidonic acid (AA), 5,8,11,14-eicosateraenoic acid is abundant, active and necessary in the human body. In the present study, we reported the neuroprotective effects and mechanism of arachidonic acid on hippocampal slices insulted by glutamate, NaN(3) or H(2)O(2)in vitro. Different types of models of brain injury in vitro were developed by 1mM glutamate, 10mM NaN(3) or 2mM H(2)O(2). After 30 min of preincubation with arachidonic acid or linoleic acid, hippocampal slices were subjected to glutamate, NaN(3) or H(2)O(2), then the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride method. Endogenous antioxidant enzymes activities (SOD, GSH-PX and catalase) in hippocampal slices were evaluated during the course of incubation. MK886 (5 microM; a noncompetitive inhibitor of proliferator-activated receptor [PPAR]alpha), BADGE (bisphenol A diglycidyl ether; 100 microM; an antagonist of PPARgamma) and cycloheximide (CHX; 30 microM; an inhibitor of protein synthesis) were tested for their effects on the neuroprotection afforded by arachidonic acid. Population spikes were recorded in randomly selected hippocapal slices. Arachidonic acid (1-10 microM) dose dependently protected hippocampal slices from glutamate and H(2)O(2) injury (P<0.01), and arachidonic acid (10 microM) can significantly improve the activities of Cu/Zn-SOD in hippocampal slices after 1h incubation. In addition, 10 microM arachidonic acid significantly increased the activity of Mn-SOD and catalase, and decreased the activities of Cu/Zn-SOD to control value after 3h incubation. These secondary changes of SOD during incubation can be reversed by indomethacine (10 microM; a nonspecific cyclooxygenase inhibitor) or AA 861 (20 microM; a 5-lipoxygenase inhibitor). Its neuroprotective effect was completely abolished by BADGE and CHX. These observations reveal that arachidonic acid can defense against oxidative stress by boosting the internal antioxidant system of hippocampal slices. Its neuroprotective effect may be mainly mediated by the activation of PPARgamma and synthesis of new protein in tissue.

Do Ureaplasma urealyticum infections in the genital tract affect semen quality?

UNLABELLED: To investigate the relationship between Ureaplasma urealyticum (UU) infection and semen quality. METHODS: From 2001 to 2003, 346 eligible patients aged 20-45 years were invited from two hospitals in Shanghai, China, to participate in an investigation which included questionnaires about general and reproductive health, an external genital tract examination, UU culture and semen analysis. Multiple linear regression models were used to examine whether UU had a significant effect on semen quality after adjustment for confounding factors. RESULTS: Findings suggested that UU infection was associated with higher semen viscosity and lower semen pH value. Sperm concentration was lower in UU positive subjects than that in UU negative subjects (54.04 X 10(6)/mL vs.70.58 X 10(6)/mL). However, UU did not significantly affect other semen quality indexes. CONCLUSION: UU infection of the male genital tract could negatively influence semen quality.