Effects of nanoparticle zinc oxide on spatial cognition and synaptic plasticity in mice with depressive-like behaviors

Background: Nanomaterials, as a new kind of materials, have been greatly applied in different fields due to their special properties. With the industrialization of nanostructured materials and increasing public exposure, the biosafety and potential influences on central nervous system (CNS) have received more attention. Nanosized zinc oxide (nanoZnO) was suggested to up-regulate neuronal excitability and to induce glutamate release in vitro. Therefore, we hypothesized nanoparticles of nanoZnO may lead to changes in balance of neurotransmitter or neuronal excitability of CNS. This study was to investigate if there were effects of nanoZnO on animal model of depression. Methods: Male Swiss mice were given lipopolysaccharides (LPS, 100 mu g/kg, 100 mu g/ml, every other day, 8 times, i.p.) from weaning to induce depressive-like behaviors. NanoZnO (5.6 mg/kg, 5.6 mg/ml, every other day, 8 times, i.p.) was given as the interaction. The mouse model was characterized using the methods of open field test, tail suspension test and forced swim test. Furthermore, the spatial memory was evaluated using Morris water maze (MWM) and the synaptic plasticity was assessed by measuring the long-term potentiation (LTP) in the perforant pathway (PP) to dentate gyrus (DG) in vivo. Results: Results indicated that model mice showed disrupted spatial memory and LTP after LPS injections and the behavioral and electrophysiological improvements after nanoZnO treatment. Conclusion: Data suggested that nanoZnO may play some roles in CNS of mental disorders, which could provide some useful direction on the new drug exploring and clinical researches.Peer reviewe

Inhibitory effect of tungsten carbide nanoparticles on voltage-gated potassium currents of hippocampal CA1 neurons

The effects of tungsten carbide nanoparticles (nano-WC) on the properties of voltage-dependent potassium currents and evoked action potentials were studied in the hippocampal CA1 pyramidal neurons of rats at the ages of postnatal days 10-14 using the whole-cell patch-clamp technique. The results indicated that: (1) the amplitudes of transient outward potassium current (I A) and delayed rectifier potassium current (I K) were significantly decreased by 10 -7g/ml nano-WC, while the current-voltage curves of I A and I K were significantly decreased by nano-WC from +10 to +90mV. (2) Nano-WC produced a depolarizing shift in the steady-state activation curve of I A and I K with increased slope factors, and delayed the recovery of I A from inactivation, but no significant effects were found on the inactivation of I A. (3) Nano-WC prolonged the evoked action potential duration and lowered the firing rate. These results suggest that 10 -7g/ml nano-WC can decrease the amplitudes of I A and I K currents by reducing the opening number of voltage-gated potassium channels and delaying the recovery of I A from inactivation, which indicate that nano-WC has the potential neurotoxicity.Peer reviewe

Attenuated effect of tungsten carbide nanoparticles on voltage-gated sodium current of hippocampal CA1 pyramidal neurons

Nanomaterials and relevant products are now being widely used in the world, and their safety becomes a great concern for the general public. Tungsten carbide nanoparticles (nano-WC) are widely used in metallurgy, aeronautics and astronautics, however our knowledge regarding the influence of nano-WC on neurons is still lacking. The aim of this study was to investigate the impact of nano-WC on tetrodotoxin (TTX)-sensitive voltage-activated sodium current (I(Na)) of hippocampal CA1 pyramidal neurons. Results showed that acute exposure of nano-WC attenuated the peak amplitudes of I(Na) in a concentration-dependent manner. The minimal effective concentration was 10(-5)g/ml. The exposure of nano-WC significantly decreased current amplitudes of the current-voltage curves of I(Na) from -50 to+50 mV, shifted the steady-state activation and inactivation curves of I(Na) negatively and delayed the recovery of I(Na) from inactivation state. After exposure to nano-WC, the peak amplitudes, overshoots and the V-thresholds of action potentials (APs) were markedly reduced. These results suggested that exposure of nano-WC could influence some characteristics of APs evoked from the hippocampal CA1 neurons by modifying the kinetics of voltage-gated sodium channels (VGSCs).Peer reviewe

Changes in phenolic profiles and antioxidant activity in rabbiteye blueberries during ripening

Blueberry (Vaccinium spp.) is a widely consumed fruit worldwide. Anthocyanins, phenolic acids, and flavonoids are the main bioactive compounds of blueberry. However, little information is available about the changes in phenolic profiles of blueberries during fruit maturation. The aim of this work was to assess the effects of genotype and maturity on phenolic compounds and antioxidant ability of four rabbiteye blueberry cultivars grown in Guizhou, China. The total phenolics, total flavonoid and individual phenolic compound in the rabbiteye blueberries were investigated at five ripening stages based on color. Derivatives of phenolic compounds (gallic acid, epicatechin, rutin, p-coumaric acid, quercetin, catechin, ellagic acid, chlorogenic acid, and ferulic acid) were determined by HLPC and quantified using calibration curves. Antioxidant capacity was evaluated by total reducing power assay (TRPA), 1,1-diphenyl-2- picrylhydrazyl (DPPH), ferric ion reducing antioxidant power (FRAP), and 2,2ʹ-Azinobis-(3-ethylbenzthiazoline-6-sulfonate (ABTS) assay. Gallic acid, ellagic acid, and ferulic acid were the main phenolic compounds in rabbiteye blueberries, and phenolic compound contents of different rabbiteye blueberries cultivars changed with ripening stage. The gallic acid content of all cultivars increased at first and then decreased. The ferulic acid contents of ‘Powderblue’ and ‘Gardenblue’ cultivars gradually increased during ripening. The ellagic acid content of ‘Powderblue’ blueberries increased with ripening but decreased in ‘Baldwin’ blueberries. The total phenolics, total flavonoid, and antioxidant capacity of all cultivars increased nonlinearly with ripening. Phenolic compounds were the main antioxidants found in rabbiteye blueberries. Notably, ‘Gardenblue’ had exceptionally higher phenolics compound and antioxidant activity compared with other cultivars

HDAC9 deficiency promotes tumor progression by decreasing the CD8+ dendritic cell infiltration of the tumor microenvironment

Background The tumor microenvironment (TME) contains a variety of immune cells, which play critical roles during the multistep development of tumors. Histone deacetylase 9 (HDAC9) has been reported to have either proinflammatory or anti-inflammatory effects, depending on the immune environment. In this study, we investigated whether HDAC9 in the tumor stroma regulated inflammation and antitumor immunity.Methods Hdac9 knockout mice were generated to analyze the HDAC9-associated inflammation and tumor progression. Immune cells and cytokines in TME or draining lymph nodes were quantified by flow cytometry and quantitative reverse transcription-PCR. The antigen presentation and CD8+ T cell priming by tumor-infiltrating dendritic cells (DCs) were evaluated in vitro and in vivo. HDAC9-associated inflammation was investigated in a mouse model with dextran sulfate sodium–induced colitis. Correlation of HDAC9 with CD8+ expression was assessed in tissue sections from patients with non-small cell lung cancer.Results HDAC9 deficiency promoted tumor progression by decreasing the CD8+ DC infiltration of the TME. Compared with wild-type mice, the tumor-infiltrating DCs of Hdac9-/- mice displayed impaired cross-presentation of tumor antigens and cross-priming of CD8+ T cells. Moreover, HDAC9 expression was significantly positively correlated with CD8+ cell counts in human lung cancer stroma samples.Conclusions HDAC9 deficiency decreased inflammation and promoted tumor progression by decreasing CD8+ DC infiltration of the TME. HDAC9 expression in the tumor stroma may represent a promising biomarker to predict the therapeutic responses of patients receiving CD8+ T cell-dependent immune treatment regimens

An engineered Cas12i nuclease that is an efficient genome editing tool in animals and plants

Summary: The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing. However, natural nucleases of this system often exhibit low efficiency, limiting their application. Here, we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease, Cas12i3. As a result, we developed Cas-SF01, a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian cells. Cas-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 nucleases. Compared to natural Cas12i3, Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN PAMs. In addition, we identified an amino acid substitution, D876R, that markedly reduced the off-target effect while maintaining high on-target activity, leading to the development of Cas-SF01HiFi (high-fidelity Cas-SF01). Finally, we show that Cas-SF01 has high gene editing activities in mice and plants. Our results suggest that Cas-SF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms