Inhibition of melanoma using a nanoceria-based prolonged oxygen-generating phototherapy hydrogel.

Tumor hypoxic environment is an inevitable obstacle for photodynamic therapy (PDT) of melanoma. Herein, a multifunctional oxygen-generating hydrogel loaded with hyaluronic acid-chlorin e6 modified nanoceria and calcium peroxide (Gel-HCeC-CaO2) was developed for the phototherapy of melanoma. The thermo-sensitive hydrogel could act as a sustained drug delivery system to accumulate photosensitizers (chlorin e6, Ce6) around the tumor, followed by cellular uptake mediated by nanocarrier and hyaluronic acid (HA) targeting. The moderate sustained oxygen generation in the hydrogel was produced by the reaction of calcium peroxide (CaO2) with infiltrated H2O in the presence of catalase mimetic nanoceria. The developed Gel-HCeC-CaO2 could efficiently alleviate the hypoxia microenvironment of tumors as indicated by the expression of hypoxia-inducible factor -1α (HIF-1α), meeting the "once injection, repeat irradiation" strategy and enhanced PDT efficacy. The prolonged oxygen-generating phototherapy hydrogel system provided a new strategy for tumor hypoxia alleviation and PDT.

Neuronal loss without amyloid-ß deposits in the thalamus and hippocampus in the late period after middle cerebral artery occlusion in cynomolgus monkeys.

Conflicting evidence exists regarding whether focal cerebral infarction contributes to cerebral amyloid-ß (Aß) deposition, as observed in Alzheimer's disease. In this study, we aimed to evaluate the presence of Aß deposits in the ipsilateral thalamus and hippocampus 12 months post-stroke in non-human primates, whose brains are structurally and functionally similar to that of humans. Four young male cynomolgus monkeys were subjected to unilateral permanent middle cerebral artery occlusion (MCAO), and another four sham-operated monkeys served as controls. All monkeys underwent magnetic resonance imaging examination on post-operative day 7 to assess the location and size of the infarction. The numbers of neurons, astrocytes, microglia and the Aß load in the non-affected thalamus and hippocampus ipsilaterally remote from infarct foci were examined immunohistochemically at sacrifice 12 months after operation. Thioflavin S and Congo Red stainings were used to identify amyloid deposits. Multiple Aß antibodies recognizing both the N-terminal and C-terminal epitopes of Aß peptides were used to avoid antibody cross-reactivity. Aß levels in cerebrospinal fluid (CSF) and plasma were examined using enzyme-linked immunosorbent assay. The initial infarct was restricted to the left temporal, parietal, insular cortex and the subcortical white matter, while the thalamus and hippocampus remained intact. Of note, there were fewer neurons and more glia in the ipsilateral thalamus and hippocampus in the MCAO group at 12 months post-stroke compared to the control group (all P < 0.05). However, there was no sign of extracellular Aß plaques in the thalamus or hippocampus. No statistically significant difference was found in CSF or plasma levels of Aß40 , Aß42 or the Aß40 /Aß42 ratio between the two groups (P > 0.05). These results suggest that significant secondary neuronal loss and reactive gliosis occur in the non-affected thalamus and hippocampus without Aß deposits in the late period after MCAO in non-human primates.

Nitrate and nitrite content in bottled beverages by ion-pair high-performance liquid chromatography.

Nitrate and nitrite levels in six types of beverages--total of 292 individual samples from 73 brands (four bottles each)--from Guangzhou city in China were evaluated by ion-pair high-performance liquid chromatography. All samples contained nitrate. Nitrate and nitrite ranges were 0.43-46.08 and <0.005-0.501 mg/L, respectively. The highest nitrate levels were detected in tea drinks (46.08 mg/L). For nitrite, the highest levels were found in fruit juice drinks (0.501 mg/L). Three brands of fruit juice drinks exceeded the Joint FAO/WHO Expert Committee on Food Additives provisional guideline value of 0.2 mg/L for nitrite and were considered to be hazardous for public health. This study supplies useful information on safety of Chinese bottled beverages.

Neuronal mechanisms of cortical alpha oscillations in awake-behaving macaques.

Field potential oscillations at approximately 10 Hz (alpha rhythm) are widely noted in the visual cortices, but their physiological mechanisms and significance are poorly understood. In vitro studies have implicated pyramidal neurons in both infragranular and supragranular layers as pacemakers. The generality of these observations for the intact brain in the behaving subject is unknown. We analyzed laminar profiles of spontaneous local field potentials and multiunit activity (MUA) recorded with linear array multielectrodes from visual areas V2, V4, and inferotemporal (IT) cortex of two macaque monkeys during performance of a sensory discrimination task. Current source density (CSD) analysis was combined with CSD-MUA coherence to identify intracortical alpha current generators and their potential for alpha pacemaking. The role of each alpha current generator was further delineated by Granger causality analyses. In V2 and V4, alpha current generators were found in all layers, with the infragranular generator acting as primary local pacemaking generator. In contrast, in IT, alpha current generators were found only in supragranular and infragranular layers, with the supragranular generator acting as primary local pacemaking generator. The amplitude of alpha activity in V2 and V4 was negatively correlated with behavioral performance, whereas the opposite was true in IT. The alpha rhythm in IT thus appears to differ from that in the lower-order cortices, both in terms of its underlying physiological mechanism and its behavioral correlates. This work may help to reconcile some of the diverse findings and conclusions on the functional significance of alpha band oscillations in the visual system.

[Effects of pricking blood therapy on ACTH contents in the hypothalamus-pituitary-adrenal axis in the rat of experimental allergic rhinitis].

OBJECTIVE: To explore the mechanism of pricking blood therapy (PBT) for allergic rhinitis (AR). METHODS: The model rat of experimental allergic rhinitis (EAR) was established by administration of ovoglohulin and they were divided into five groups randomly: a model group, a PBT group, a TCM point application group, a beclomethasone dipropionate (BDP) treatment group, and a health control group. Adrenocorticotrophic hormone (ACTH) contents in hypothalamus, pituitary gland, adrenal gland and plasma were determined by radioimmunoassay before and after treatment. RESULTS: The ACTH levels in the hypothalamus, pituitary gland, adrenal gland and plasma in the rat of EAR were lower than those in the health control group (P < 0.01). After treatment of pricking blood ther, ACTH levels in the above tissues increased significantly (P < 0.01), with very significant differences (P < 0.01) as compared with the model group, similar to those in the BDP group (P > 0.05). CONCLUSION: Pricking blood therapy has a regulatory action on ACTH in HPA axis of rats with experimental allergic rhinitis.

[Effect of mailuoning on C-Fos protein expression in rats with cerebral infarction].

OBJECTIVE: To investigate the protective effect of mailuoning (MLN) on nerve cells after cerebral infarction induced by photochemistry. METHODS: Eighty SD rats were divided into three groups, the control group (n = 20), the model group (n = 30) and the MLN group (n = 30). Focal cerebro-ischemia induced by photothrombosis in adult rat was used as a model. Changes of C-Fos protein expression before and after MLN treatment were observed using immunohistochemistry, computerized imaging technique and transmission electron microscopy (TEM). RESULTS: C-Fos positive cells located in the transitional zone between the necrotic core and normal cortex. C-Fos protein expression began to show 3 hrs after cerebral infarction, peaked at 6 hrs. As compared with the model group, C-Fos expression was significantly reduced in the MLN group (P<0.01). CONCLUSION: MLN could markedly reduce the injury of nerve cell in the transitional zone, the protection may be related with its inhibition on C-Fos protein expression.

[High throughput screening method of nitric oxide synthase inhibitors and enhancers].

AIM: In order to discover new inhibitors and enhancers of nitric oxide synthase (NOS), an in vitro assay to determine NOS activity was established for high throughput screening. METHODS: The activity of NOS was detected based on the change of nicotinamide-adenine dinucleotide phosphate (NADPH) concentration in the reaction system by the fluorescence density. The enzyme was prepared from bovine brain by gradient centrifugation. The reaction performed in black 96 well micro-plate with a final volume of 90 microL. Every factor which would affect the results such as the concentration of NADPH, L-arginine (L-Arg, used as substrate) and enzyme protein was optimized in different conditions. At last, 5,600 samples (compounds and extracts) were screened by the method. RESULTS: The test signal (fluorescence density) in the reaction system was influenced by many different factors such as temperature and concentration of substrates. The ideal system contains protein 1.50 mg.mL-1, L-Arg 1 mmol.L-1, NADPH 0.1 mmol.L-1 at 37 degrees C. In this method, there were about 2% samples which emit fluorescence, and about 0.5% samples which quench the fluorescence. So these samples were deleted from the sample library. The effects of these samples on activity of NOS were distributed in a normal manner. About 2% samples had potential effects on the NOS activity (including inhibitors and enhancers). CONCLUSION: The method can be performed by high throughput screening and gives the stable data, not only for inhibitors, but also for enhancers of NOS activity.