Antibacterial Activity of Polymer Coated Cerium Oxide Nanoparticles

Cerium oxide nanoparticles have found numerous applications in the biomedical industry due to their strong antioxidant properties. In the current study, we report the influence of nine different physical and chemical parameters: pH, aeration and, concentrations of MgSO₄, CaCl₂, KCl, natural organic matter, fructose, nanoparticles and Escherichia coli, on the antibacterial activity of dextran coated cerium oxide nanoparticles. A least-squares quadratic regression model was developed to understand the collective influence of the tested parameters on the anti-bacterial activity and subsequently a computer-based, interactive visualization tool was developed. The visualization allows us to elucidate the effect of each of the parameters in combination with other parameters, on the antibacterial activity of nanoparticles. The results indicate that the toxicity of CeO₂ NPs depend on the physical and chemical environment; and in a majority of the possible combinations of the nine parameters, non-lethal to the bacteria. In fact, the cerium oxide nanoparticles can decrease the anti-bacterial activity exerted by magnesium and potassium salts.     

Attachment of a Frog Skin-Derived Peptide to Functionalized Cerium Oxide Nanoparticles

Peptide Brevinin-2R (B2R) has derived from frog skin secretions and possesses cytotoxic effects on cancer cells. Beside, cerium oxide nanoparticle (CNP) has antioxidant properties and could be used in anticancer studies. The purpose of this study is to investigate antioxidant and cytotoxicity of cerium oxide nanoparticle conjugated with B2R. First, cerium oxide nanoparticles were amine functionalized and peptide attached to it through establishment of peptide bond. Then, (1,1-diphenyl-2-picrylhydrazyl) DPPH and 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical scavenging activities of CNP-B2R were determined. MTT assay were used in order to compare cytotoxicity of CNP- B2R on two different cell lines. HFLF-pI5 cell and A549 cell lines were selected as representative of normal and cancer cells, respectively. Also, the cytotoxic effects of CNP, B2R and CNP-B2R were investigated on A549 cell line. Results of antioxidant evaluations showed that the antioxidant activity of CNP-Peptide increased at higher concentration of CNP-B2R with IC₅₀ of 0.2 and 0.54 (mg/mL) for DPPH and ABTS assays, respectively. The results of cytotoxicity effects showed that CNP-B2R was more potent in killing tumor cell line in comparison with normal cell line. Cytotoxicity of CNP, B2R and CNP-B2R demonstrated that CNP-B2R and B2R had the lower cell viability effects compared to CNP. Our findings showed cytotoxicity of CNP-B2R against cancer cell lines in comparison with normal cells indicating the potential anticancer properties of CNP-B2R.     

Cerium Oxide Nanoparticles Attenuate Oxidative Stress and Inflammation in the Liver of Diethylnitrosamine-Treated Mice

Biological Trace Element Research - The catalytic activity of cerium oxide nanoparticles (CeO2NPs) is responsible for its application as an antitumor agent. This activity may be due to its ability...     

Cerium Oxide Nanoparticles Protect Endothelial Cells from Apoptosis Induced by Oxidative Stress

Oxidative stress is well documented to cause injury to endothelial cells (ECs), which in turn trigger cardiovascular diseases. Previous studies revealed that cerium oxide nanoparticles (nanoceria) had antioxidant property, but the protective effect of nanoceria on ROS injury to ECs and cardiovascular diseases has not been reported. In the current study, we investigated the protective effect and underlying mechanisms of nanoceria on oxidative injury to ECs. The cell viability, lactate dehydrogenase release, cellular uptake, intracellular localization and reactive oxygen species (ROS) levels, endocytosis mechanism, cell apoptosis, and mitochondrial membrane potential were performed. The results indicated that nanoceria had no cytotoxicity on ECs but had the ability to prevent injury by H₂O₂. Nanoceria could be uptaken into ECs through caveolae- and clathrin-mediated endocytosis and distributed throughout the cytoplasma. The internalized nanoceria effectively attenuated ROS overproduction induced by H₂O₂. Apoptosis was also alleviated greatly by nanoceria pretreatment. These results may be helpful for more rational application of nanoceria in biomedical fields in the future.     

小胶质细胞的活化与阿尔茨海默病

小胶质细胞是中枢神经系统中一种巨噬细胞样吞噬细胞,具有重要的免疫细胞作用。它与阿尔茨海默病（AD）的发生和发展有关,目前认为它可能通过两种机制起作用。其一是伴随着阿尔茨海默病的特征性病理改变,小胶质细胞活化,进而引起局部炎症反应;其二是它参与了β淀粉样蛋白的清除。大量研究结果提示这两个过程是密切联系的,即：β淀粉样蛋白吸引并激活小胶质细胞,活化后小胶质细胞的一部分分泌炎症因子,引起炎症反应;而另一部分则具有吞噬β淀粉样蛋白的作用。关于这方面的研究目前还没有一致意见。     

Assessment the Exposure Level of Rare Earth Elements in Workers Producing Cerium,Lanthanum Oxide Ultrafine and Nanoparticles

In order to assess occupational exposure level of 15 rare earth elements (REEs) and identify the associated influence, we used inductively coupled plasma mass spectrometry (ICP-MS) based on closed-vessel microwave-assisted wet digestion procedure to determinate the concentration of Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu in urinary samples obtained from workers producing ultrafine and nanoparticles containing cerium and lanthanum oxide. The results suggest that La and Ce were the primary component, together accounting for 97 % of total REEs in workers. The urinary levels of La, and Ce among the workers (6.36, 15.32 μg.g^?1 creatinine, respectively) were significantly enriched compared to those levels measured in the control subjects (1.52, 4.04 μg.g^?1 creatinine, respectively) (p < 0.05). This study simultaneously identified the associated individual factors, the results indicate that the concentrations in over 5 years group (11.64 ± 10.93 for La, 27.83 ± 24.38 for Ce) were significantly elevated compared to 1–5 years group (2.58 ± 1.51 for La, 6.87 ± 3.90 for Ce) (p < 0.05). Compared the urinary levels of La and Ce at the separation and packaging locations (9.10 ± 9.51 for La, 22.29 ± 21.01 for Ce) with the other locations (2.85 ± 0.98 for La, 6.37 ± 2.12 for Ce), the results show urinary concentrations were significantly higher in workers at separation and packaging locations (p < 0.01). Inter-individual variation in levels of La and Ce in urine is the result of multi-factorial comprehensive action. Further researches should focus on the multiple factors contributing to the REEs levels of the occupationally exposed workers.     

Antibiotics and Light Responses in Superfused Bovine Retina

1. Our objective was to study effects of clindamycin and ciprofloxacin on the electroretinogram (ERG) of isolated bovine retinas.2. Electroretinograms of isolated superfused bovine retinas were recorded under normal conditions and during application of clindamycin and ciprofloxacin. The b-wave reduction was plotted against the drug concentration. In several cases retinal oxygen uptake was also measured. Clindamycin was available only in a preparation containing benzyl alcohol. To differentiate between effects caused by the antibiotic and the alcohol, ERGs were also recorded under superfusion with benzyl alcohol. To record drug effects on photoreceptors synaptic transmission was blocked using 1 mM aspartate.3. At concentrations between 0.3 and 10 mM clindamycin significantly reduced the amplitude of the b-wave of the ERG. A comparable reduction of retinal oxygen uptake was found at concentrations 10-fold higher. Clindamycin, 3 mM, did not affect the a-wave after preincubation with aspartate. Benzyl alcohol at concentrations of 0.3 and 1 mM did not affect the b-wave, whereas at higher concentrations the b-wave was found to be reduced. Considerable b-wave reductions were found with ciprofloxacin at concentrations of between 0.03 and 0.6 mM. All effects proved to be fully reversible and dose-dependent.4. Ciprofloxacin and clindamycin did both alter neural function in the isolated superfused bovine retina. The nontoxic dosages found here differ considerably from results in rabbits after intravitreal injections. This is probably due to species differences.     

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, ¹⁸F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of ¹⁸F-DPA-714 was increased in ALS patients during the “time of diagnosis” phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.     

Effects of Cerium Oxide Nanoparticles on the Proliferation, Differentiation, and Mineralization Function of Primary Osteoblasts In Vitro

The effects of cerium oxide nanoparticles on the proliferation, differentiation, and mineralization function of primary osteoblasts in vitro were evaluated. The results showed that the cell biological effects of cerium oxide nanoparticles varied with different diameters. The cytotoxicity of cerium oxide nanoparticles on primary osteoblasts varies with the size and incubation time. Sixty-nanometer cerium oxide nanoparticles show significant cytotoxicity on primary osteoblasts at 48 h exposure. Cerium oxide nanoparticles with diameters of 40 nm promoted the differentiation of osteoblasts and the promotion rate was enhanced with increasing concentration. Cerium oxide nanoparticles with diameters of 60 nm promoted the differentiation of osteoblasts at lower concentrations, but turned to inhibit the differentiation at higher concentrations. Cerium oxide nanoparticles promoted the adipogenic transdifferentiation of osteoblasts at all tested concentrations. Moreover, the effects of 60-nm cerium oxide nanoparticles were stronger than that of 40-nm cerium oxide nanoparticles. Cerium oxide nanoparticles promoted the formation of mineralized matrix nodules of osteoblasts at all tested concentrations in a dose-dependent manner and the promotion rate increased with decreasing size. The results showed that cerium oxide nanoparticles had no acute cytotoxic effects on osteoblasts and could promote the osteogenic differentiation and mineralization of osteoblasts. Moreover, the size, concentration, and culture time of nanoparticles have significant influence on the proliferation, differentiation, and mineralization of osteoblasts.     

Role and Mechanism of Microglial Activation in Iron-Induced Selective and Progressive Dopaminergic Neurodegeneration

Parkinson’s disease (PD) patients have excessive iron depositions in substantia nigra (SN). Neuroinflammation characterized by microglial activation is pivotal for dopaminergic neurodegeneration in PD. However, the role and mechanism of microglial activation in iron-induced dopaminergic neurodegeneration in SN remain unclear yet. This study aimed to investigate the role and mechanism of microglial β-nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activation in iron-induced selective and progressive dopaminergic neurodegeneration. Multiple primary midbrain cultures from rat, NOX2^+/+ and NOX2^?/? mice were used. Dopaminergic neurons, total neurons, and microglia were visualized by immunostainings. Cell viability was measured by MTT assay. Superoxide (O₂ ^·?) and intracellular reactive oxygen species (iROS) were determined by measuring SOD-inhibitable reduction of tetrazolium salt WST-1 and DCFH-DA assay. mRNA and protein were detected by real-time PCR and Western blot. Iron induces selective and progressive dopaminergic neurotoxicity in rat neuron–microglia–astroglia cultures and microglial activation potentiates the neurotoxicity. Activated microglia produce a magnitude of O₂ ^·? and iROS, and display morphological alteration. NOX2 inhibitor diphenylene iodonium protects against iron-elicited dopaminergic neurotoxicity through decreasing microglial O₂ ^·? generation, and NOX2^?/? mice are resistant to the neurotoxicity by reducing microglial O₂ ^·? production, indicating that iron-elicited dopaminergic neurotoxicity is dependent of NOX2, a O₂ ^·?-generating enzyme. NOX2 activation is indicated by the increased mRNA and protein levels of subunits P47 and gp91. Molecules relevant to NOX2 activation include PKC-σ, P38, ERK1/2, JNK, and NF-КB_P65 as their mRNA and protein levels are enhanced by NOX2 activation. Iron causes selective and progressive dopaminergic neurodegeneration, and microglial NOX2 activation potentiates the neurotoxicity. PKC-σ, P38, ERK1/2, JNK, and NF-КB_P65 are the potential molecules relevant to microglial NOX2 activation.     

Neochlorogenic Acid Inhibits Lipopolysaccharide-Induced Activation and Pro-inflammatory Responses in BV2 Microglial Cells

Neurochemical Research - Microglia is the resident innate immune cells that sense pathogens and tissue injury in the central nervous system. Microglia becomes activated in response to injury,...     

Effects of Light on Dopamine Metabolism in the Chick Retina

The effect of prolonged exposure to light on the activity of dopaminergic neurons and dopamine (DA) metabolism of chick retinae was investigated. alpha-Fluoromethyldopa, a potent and specific irreversible inactivator of aromatic amino acid decarboxylase, was used to assess DA turnover after inhibition of synthesis, and also to assess in vivo tyrosine hydroxylase activity by dihydroxyphenylalanine accumulation. After 48 h of light exposure, retinal DNA in 12-day-old chicks was about 30% higher (p less than 0.005) whereas dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were elevated two to three times (p less than 0.005) the level of controls kept in the dark for the same period. DA turnover was about twofold faster in the light (t 1/2 = 31 min) than in the dark (t 1/2 = 65 min). Tyrosine hydroxylase, assayed in vitro with saturating levels of cofactor and substrate, increased by about 50% after light exposure. The apparent tyrosine hydroxylase activity in vivo was approximately sixfold higher in the light than the dark. These results are interpreted and discussed in terms of the regulation of DA synthesis, and the use of DOPAC and HVA as indices of DA function in the retina.     

Attenuation of Dichlorvos-Induced Microglial Activation and Neuronal Apoptosis by 4-Hydroxy TEMPO

The neurotoxic consequences of acute high-level as well as chronic low-level organophosphates exposure are associated with a range of abnormalities in nerve functions. Previously, we have shown that after 24 h of dichlorvos exposure, microglia become activated and secrete pro-inflammatory molecules like nitric oxide, tumour necrosis factor-α and interleukin-1β. Here, we extended our findings and focused on the neuronal damage caused by dichlorvos via microglial activation. For this, neurons and microglia were isolated separately from 1-day-old Wistar rat pups. Microglia were treated with dichlorvos for 24 h and supernatant was collected (dichlorvos-induced conditioned medium, DCM). However, when 4-hydroxy TEMPO (4-HT) pretreatment was given, we observed significant attenuation of dichlorvos-induced microglial activation; we also collected the supernatant of this culture (4-HT + DCM, TDCM). Next, we checked the effects of DCM on neurons and found heavy loss in viability as evident from NF-H immunostaining and MTT results, whereas dichlorvos alone-treated neurons showed comparatively less damage. However, we observed significant increase in neuronal viability when cells were treated with TDCM. Semi-quantitative PCR and western blot results revealed significant increase in p53, Bax and cytochrome c levels along with caspase 3 activation after 24 h of DCM treatment. However, TDCM-treated neurons showed significant decrease in the expression of these pro-apoptotic molecules. Taken together, these findings suggest that 4-HT can significantly attenuate dichlorvos-induced microglial activation and prevent apoptotic neuronal cell death.     

Melatonin Alters the miRNA Transcriptome of Inflammasome Activation in Murine Microglial Cells

Neurochemical Research - Systemic inflammation can have devastating effects on the central nervous system via its resident immune cells, the microglia. One of the primary mediators of this...     

Iron Oxide Nanoparticles Induce Oxidative Stress,DNA Damage,and Caspase Activation in the Human Breast Cancer Cell Line

Broad applications of iron oxide nanoparticles require an improved understanding of their potential effects on human health. In the present study, we explored the underlying mechanism through which iron oxide nanoparticles induce toxicity in human breast cancer cells (MCF-7). MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) and lactate dehydrogenase assays were used to examine mechanisms of cytotoxicity. Concentration- and time-dependent cytotoxicity was observed in MCF-7 cells. Iron oxide nanoparticles were found to induce oxidative stress evidenced by the elevation of reactive oxygen species generation, lipid peroxidation, and depletion of superoxide dismutase, glutathione, and catalase activities in MCF-7 cells. Nuclear staining was performed using 4′, 6-diamidino-2-phenylindole (DAPI), and cells were analyzed with a fluorescence microscope. Iron oxide nanoparticles (60 μg/ml) induced substantial apoptosis that was identified by morphology, condensation, and fragmentation of the nuclei of the MCF-7 cells. It was also observed that the iron oxide NPs induced caspase-3 activity. DNA strand breakage was detected by comet assay, and it occurred in a concentration- and time-dependent manner. Thus, the data indicate that iron oxide nanoparticles induced cytotoxicity and genotoxicity in MCF-7 cells via oxidative stress. This study warrants more careful assessment of iron oxide nanoparticles before their industrial applications.