Glutathione alleviates acute intracerebral hemorrhage injury via reversing mitochondrial dysfunction.

Glutathione (GSH) has been studied for its neuroprotection value in several diseases, but the effect of GSH on intracerebral hemorrhage (ICH) is unclear. In this study, we examined the protective effects of GSH in an experimentally induced ICH model and investigated the relative mechanisms. Adult male C57BL/6j mice were randomized into Sham, ICH and GSH treatment groups. GSH was injected with the dose of 50, 100 or 200 mg/kg once per day for 3 days, starting immediately after operation. The results revealed a GSH-mediated improvement of neurological deficits score (NDS), motor and sensory functions impairment in a dose-dependent manner three days post ICH (p < 0.01, GSH 200 vs ICH. Sham, n = 12; ICH, n = 9; GSH 50, n = 10; GSH 100, n = 10; GSH 200, n = 11) in addition to significantly reduced mortality rate (p = 0.2632, GSH 200 vs ICH. n = 12 per group) and damage volume (p < 0.05, GSH 200 vs ICH. n = 12 per group). GSH treatment also attenuated injury measured by decreased brain edema (p < 0.05, GSH 200 vs ICH. Sham, n = 10; ICH, n = 10; GSH 200, n = 12), blood-brain barrier disruption (p < 0.05, GSH 200 vs ICH. Sham, n = 10; ICH, n = 10; GSH 200, n = 12), and histopathological damage (p < 0.05, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8) 72 h after ICH. In addition, GSH treatment also decreased cell apoptosis (p < 0.01, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8) and resulted in up-regulated protein expression of complex I (p < 0.01, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8), which was consistent with an overall up-regulation of complex I function in mitochondria using Oxygraph-2 K high resolution respirometry (p < 0.05, GSH 200 vs ICH. Sham, n = 4; ICH, n = 5; GSH 200, n = 6). In conclusion, GSH effectively improved the prognosis of ICH mice by attenuating neurological impairment, decreasing neural damage, and inhibiting apoptosis. The neuroprotection by GSH resulted from the up-regulation of mitochondrial oxidative respiration function. The results of our study suggest that GSH can be a potential therapeutic agent for ICH.

Changes in hormones of the hypothalamic-pituitary-gonadal axis in migraine patients.

The incidence of migraine is higher in women than in men. Abnormality of the hypothalamus-pituitary-gonadal (HPG) axis is believed to be implicated in the pathogenesis of migraine. The aim of this study was to detect serum hormone levels in the HPG axis of migraineurs and analyze the relationship between the hormone levels and migraine-related clinical characteristics. One hundred and nineteen migraineurs were enrolled. Serum FSH, LH, estradiol, progesterone, testosterone, prolactin and GnRH was detected. Pain intensity and migraine-related disability were evaluated using the visual analogue scale (VAS) and the Migraine Disability Assessment questionnaire (MIDAS). The relationships between sex hormone levels and the VAS score and the MIDAS score were also examined. Progesterone levels in male migraineurs were lower than those in healthy controls (P < .01). In female patients, in the follicular phase, testosterone levels were lower than in healthy controls (P < .01). In the luteal phase, estrogen and testosterone levels (P < .05) were lower than in healthy controls. Progesterone and testosterone levels (P < .01) were lower than in healthy controls in the postmenopausal phase. In male patients, estrogen levels were negatively associated with the MIDAS score (r = -0.602). In female patients, in the follicular phase, estrogen levels were positively correlated with headache duration and VAS score (r = 0.374, r = 0.331, respectively) and negatively related with MIDAS score (r = -0.334). In the luteal phase, estrogen and progesterone levels were negatively correlated with the MIDAS score (r = -0.772, r = -0.464, respectively). The levels of HPG axis hormones were abnormal in migraineurs and were associated with migraine-related clinical characteristics.

Water-dispersible, pH-stable and highly-luminescent organic dye nanoparticles with amplified emissions for in vitro and in vivo bioimaging.

A new strategy is presented for using doped small-molecule organic nanoparticles (NPs) to achieve high-performance fluorescent probes with strong brightness, large Stokes shifts and tunable emissions for in vitro and in vivo imaging. The host organic NPs are used not only as carriers to encapsulate different doped dyes, but also as fluorescence resonance energy transfer donors to couple with the doped dyes (as acceptors) to achieve multicolor luminescence with amplified emissions (AE). The resulting optimum green emitting NPs show high brightness with quantum yield (QY) of up to 45% and AE of 12 times; and the red emitting NPs show QY of 14% and AE of 10 times. These highly-luminescent doped NPs can be further surface modified with poly(maleic anhydride-alt-1-octadecene)-polyethylene glycol (C18PMH-PEG), endowing them with excellent water dispersibility and robust stability in various bio-environments covering wide pH values from 2 to 10. In this study, cytotoxicity studies and folic acid targeted cellular imaging of these multicolor probes are carried out to demonstrate their potential for in vitro imaging. On this basis, applications of the NP probes in in vivo and ex vivo imaging are also investigated. Intense fluorescent signals of the doped NPs are distinctly, selectively and spatially resolved in tumor sites with high sensitivity, due to the preferential accumulation of the NPs in tumor sites through the passive enhanced permeability and retention effect. The results clearly indicate that these doped NPs are promising fluorescent probes for biomedical applications.

Carrier-free, functionalized drug nanoparticles for targeted drug delivery.

We demonstrate a new concept of carrier-free functionalized drug nanoparticles for targeted drug delivery. It exhibits significantly enhanced drug efficacy to folate receptor-positive cells with high selectivity and a high drug loading content up to more than 78%.

Carrier-free, water dispersible and highly luminescent dye nanoparticles for targeted cell imaging.

We develop a new strategy of using surface functionalized small molecule organic dye nanoparticles (NPs) for targeted cell imaging. Organic dye (2-tert-butyl-9,10-di(naphthalen-2-yl)anthracene, TBADN) was fabricated into NPs and this was followed by surface modification with an amphipathic surfactant poly(maleic anhydride-alt-1-octadecene)-polyethylene glycol (C18PMH-PEG) through hydrophobic interactions to achieve good water dispersibility and bio-environmental stability. It should be noted that no additional inert materials were added as carriers, thus the dye-loading capacity of the resulting TBADN NPs is obviously higher than those of previously reported carrier-based structures. This would lead to much larger absorption and then much higher brightness. The resulting TBADN NPs possess comparable, if not higher, brightness than CdSe/ZnS quantum dots under the same conditions, with favorable biocompatibility. Significantly, TBADN NPs are readily conjugated with folic acid, and successfully applied in targeted cell imaging. These results show that water dispersible and highly stable organic NPs would be a promising new class of fluorescent probe for bioapplications in cellular imaging and labeling. This strategy may be straightforwardly extended to other organic dyes to achieve water dispersible NPs for cell imaging and drug delivery.

Determination of iron monosulfide and iron disulfide in suspensions by an electrochemical method using a platinum-silver twin-electrode.

New electrochemical technique with a Pt-Ag twin electrode is proposed for the determining the contents of iron sulfides (FeS and FeS(2)) in a suspension. After electrolytic oxidation with a Pt electrode, Fe(2+) was measured by linear sweep voltammetry. From relations of the charge amount from the baseline to the peak in the voltammogram of Fe(2+) with the content of FeS or FeS(2), linear calibration curves (a) and (b) were prepared, respectively. After measurements of Fe(2+), Fe(2+) and S(0) were reduced with a Pt electrode to remove Fe(2+) and to produce S(2-). With an Ag electrode, Ag(2)S was deposited on Ag. A linear curve (c) was prepared from a relation between the charge amount of the Ag(2)S peak part and the FeS content. However, in the suspension of FeS(2), Ag(2)S can not be detected. When this method is applied to a mixed suspension of FeS and FeS(2), the content of FeS can be determined with curve (c), whereas curves (a) and (b) were not effective in the mixed suspension.