Altered static and dynamic functional connectivity of the default mode network across epilepsy subtypes in children: A resting-state fMRI study.

BACKGROUND: Epilepsy is a chronic neurologic disorder characterized by abnormal functioning of brain networks, making it a complex research topic. Recent advancements in neuroimaging technology offer an effective approach to unraveling the intricacies of the human brain. Within different types of epilepsy, there is growing recognition regarding ongoing changes in the default mode network (DMN). However, little is known about the shared and distinct alterations of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in DMN among epileptic subtypes, especially in children with epilepsy. METHODS: Here, 110 children with epilepsy at a single center, including idiopathic generalized epilepsy (IGE), frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE), and parietal lobe epilepsy (PLE), as well as 84 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (fMRI) scan. We investigated both sFC and dFC between groups of the DMN. RESULTS: Decreased static and dynamic connectivity within the DMN subsystem were shared by all subtypes. In each epilepsy subtype, children with epilepsy displayed significant and distinct patterns of DMN connectivity compared to the control group: the IGE group showed reduced interhemispheric connectivity, the FLE group consistently demonstrated disturbances in frontal region connectivity, the TLE group exhibited significant disruptions in hippocampal connectivity, and the PLE group displayed a notable decrease in parietal-temporal connectivity within the DMN. Some state-specific FC disruptions (decreased dFC) were observed in each epilepsy subtype that cannot detect by sFC. To determine their uniqueness within specific subtypes, bootstrapping methods were employed and found the significant results (IGE: between PCC and bilateral precuneus, FLE: between right middle frontal gyrus and bilateral middle temporal gyrus, TLE: between left Hippocampus and right fusiform, PLE: between left angular and cingulate cortex). Furthermore, only children with IGE exhibited dynamic features associated with clinical variables. CONCLUSIONS: Our findings highlight both shared and distinct FC alterations within the DMN in children with different types of epilepsy. Furthermore, our work provides a novel perspective on the functional alterations in the DMN of pediatric patients, suggesting that combined sFC and dFC analysis can provide valuable insights for deepening our understanding of the neuronal mechanism underlying epilepsy in children.

Antibacterial Effect of 2R,3R-dihydromyricetin on the Cellular Functions of Staphylococcus aureus.

The C-3-OH, C-4 carbonyl oxygen and hydrogenation of C2=C3 bond on the C-ring of 2R,3R-dihydromyricetin (DMY) proved to be not necessary for the antibacterial activity against Staphylococcus aureus. DMY significantly decreased the intracellular ATP of S. aureus cells but had few effects on pHin, proline oxidation, succinate dehydrogenase activity or malate dehydrogenase activity.

Characterization of steryl glycosides in marine microalgae by gas chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS).

BACKGROUND: Steryl glycosides (SGs) are sterol conjugates found in various plants, especially in those making up human diets. It has been demonstrated that SGs have potential health benefits, and they could be used as food supplements in a variety of food matrixes. Marine microalgae are a potential resource for human food and ingredients. In this study, gas chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS) was used to characterize unknown SGs in eight microalgae belonging to different classes (Isochrysis galbana 3011, Pavlova viridis, Platymonas helgolandica, Conticribra weissflogii, Thalassiosira pseudonana, Nitzschia closterium, Gymnodinium sp., and Karlodinum veneficum). RESULTS: The SGs were first extracted from lyophilized algae with chloroform-methanol, purified by solid-phase extraction and analyzed as trimethylsilyl derivatives. Nine SGs have been identified. In particular, new SGs like occelasteryl glycoside and stellasteryl glycoside were found in Gymnodinium sp., 24-methylene cholesteryl glycoside was detected in P. helgolandica, and 4,24-dimethylcholestan-3-yl glycoside was identified as the main constituent of microalga K. veneficum. The results also showed that the compositions of SGs in different microalgae varied, with a range of 5.234 to 0.036 g kg-1 , and microalga P. viridis contained the most abundant SGs. CONCLUSION: GC-QQQ-MS is a powerful tool to detect SGs with different structures from a variety of microalgae. The compositions of SGs in different microalgae varied greatly. Microalgae are a good source of highly valued SGs. © 2017 Society of Chemical Industry.

Proximate, amino acid and lipid compositions in Sinonovacula constricta (Lamarck) reared at different salinities.

BACKGROUND: Sinonovacula constricta is an economically and nutritionally important bivalve native to the estuaries and mudflats of China, Japan and Korea. In the present study, S. constricta, cultured either under experimental conditions or collected directly from natural coastal areas with different seawater salinities, was investigated for changes in proximates, amino acids and lipids. RESULTS: When culture salinity was increased, levels of moisture, carbohydrate, crude protein and crude lipid were significantly decreased, whereas the level of ash was significantly increased. The level of Ala was increased by 1.5- to 2-fold, whereas the contents of most lipids were significantly decreased, and the proportion of phosphatidylethanolamine was significantly increased. Notably, a high proportion of ceramide aminoethylphosphonates was detected in S. constricta reared at all salinities. The energy content appears to be higher in S. constricta reared at higher salinity. In experimental S. constricta, when the salinity was enhanced, the changes of compositions were very close to those reared at constant high salinity. CONCLUSION: Sinonovacula constricta reared at higher salinities possesses a superior quality. A short period of exposure to a higher salinity for farmed S. constricta reared at a lower salinity before harvest would be useful with respect to improving its nutritive value. © 2017 Society of Chemical Industry.

Abnormal static and dynamic functional network connectivity of the whole-brain in children with generalized tonic-clonic seizures.

Introduction: Generalized tonic-clonic seizures (GTCS) are a subtype of generalized seizures exhibiting bursts of bilaterally synchronous generalized spike-wave discharges. Numerous neuroimaging studies have reported aberrant functional activity and topological organization of brain network in epilepsy patients with GTCS, but most studies have focused on adults. However, the effect of GTCS on the spatial and temporal properties of brain function in children remains unclear. The present study aimed to explore whole-brain static (sFC) and dynamic functional connectivity (dFC) in children with GTCS. Methods: Twenty-three children with GTCS and 32 matched healthy controls (HCs) were recruited for the present study. Resting-state functional magnetic resonance imaging (MRI) data were collected for each subject. The group independent component analysis method was used to obtain independent components (ICs). Then, sFC and dFC methods were applied and the differences in functional connectivity (FC) were compared between the children with GTCS and the HCs. Additionally, we investigated the correlations between the dFC indicators and epilepsy duration. Results: Compared to HCs, GTCS patients exhibited a significant decrease in sFC strengths among most networks. The K-means clustering method was implemented for dFC analysis, and the optimal number of clusters was estimated: two discrete connectivity configurations, State 1 (strong connection) and State 2 (weak connection). The decreased dFC mainly occurred in State 1, especially the dFC between the visual network (VIS) and somatomotor network (SMN); but the increased dFC mainly occurred in State 2 among most networks in GTCS children. In addition, GTCS children showed significantly shorter mean dwell time and lower fractional windows in stronger connected State 1, while GTCS children showed significantly longer mean dwell time in weaker connected State 2. In addition, the dFC properties, including mean dwell time and fractional windows, were significantly correlated with epilepsy duration. Conclusion: Our results indicated that GTCS epilepsy not only alters the connectivity strength but also changes the temporal properties of connectivity in networks in the whole brain. These findings also emphasized the differences in sFC and dFC in children with GTCS. Combining sFC and dFC methods may provide more comprehensive understanding of the abnormal changes in brain architecture in children with GTCS.

[Retracted] MicroRNA­326 inhibits cell proliferation and invasion, activating apoptosis in hepatocellular carcinoma by directly targeting LIM and SH3 protein 1.

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that various panels showing data from flow cytometric experiments in Figs. 2E, 5E and 6E, and the cell migration and invasion assay data shown in Fig. 2D and 6D, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere when it was submitted to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 1569­1578, 2017; DOI: 10.3892/or.2017.5810].

Pharmacogenomics of oxcarbazepine in the treatment of epilepsy.

Oxcarbazepine (OXC) is one of the preferred drugs for partial seizures and generalized tonic-clonic seizures. However, clinical studies have found that there are considerable differences among different populations in OXC therapeutic efficacy or safety that result from the function changes of metabolic enzymes, transporters and other receptors involved in pharmacokinetics and pharmacodynamics in vivo. The authors collected all the information on the clinically reported associations between variants of common genes (e.g., UGT1A9, HLA-B, ABCB1) and OXC. In conclusion, these associations based on variants are beneficial for adjusting the medication regimen, which could be useful for individualized treatment with OXC.

As a new-generation aromatic antiepileptic drug, oxcarbazepine (OXC) is often used for epilepsy treatment. It is known that when OXC is absorbed, it is reduced to an active metabolite in the liver and enters the brain through the blood circulation to play an antiepileptic role. Therefore, the variations of proteins participating in the process, including drug metabolic enzymes, transporters, drug targets and other receptors, have an effect on the efficacy and safety of OXC in vivo. In this study, the associations of some variants of common genes with OXC are summarized to provide epileptic patients an appropriate dose of OXC or reduce the risk of OXC-induced toxicity, which are in favor of personalized OXC treatment for patients with epilepsy.

[Study on the genotoxicity of cefuroxime lactone--an impurity substance in antibiotics].

OBJECTIVE: To study the genotoxicity of cefuroxime lactone, a kind of impurity in cefuroxime sodium, and to provide experimental basis for the toxicological safety evaluation of cefuroxime sodium. METHODS: A set of efficient and convenient genetic toxicity tests were used to evaluate the genotoxicity of cefuroxime lactone, focusing on gene mutation, chromosomal aberration, DNA damage and repair. RESULTS: (1) Ames assay: The number of colonies with back mutation (revertant) in varied strains of Salmonella typhimurium (TA97, 98, 100 and 102) through all doses of cefuroxime lactone did not exceed the number of spontaneous mutation colony by two times with or without rat liver microsomal enzymes (S9). (2) Micronucleus test in Kunming mice: Micronucleus rate in mice treated with 40 mg/kg cyclophosphamide, which used as a positive control, was 19.74 per thousand, significantly higher than that of negative control (1.82 per thousand) (P < 0.05), and micronucleus rate in mice dosed by 125, 250 and 500 (mg/kg) of cefuroxime lactone were 3.06 per thousand, 2.83 per thousand and 3.24 per thousand, showing no significant difference when compared with the negative control (P > 0.05). (3) Chromosome aberration assay: In the conditions of S9 existence or not, the chromosomal aberration rate of positive control (20 microg/ml cyclophosphamide and 0.1 microg/ml mitomycin c) was significantly higher than that of negative control (P < 0.05), while chromosomal aberration rate from cefuroxime lactone revealed no significant difference compared with the negative control (P > 0.05). (4) TK gene mutation assay: The relative survival (RS), relative viability (RV), relative suspension growth (RSG) and relative total growth (RTG) was decreased along with the increase of cefuroxime lactone concentrations, however, no significant difference was discovered between the dosed groups and negative control for TK gene mutation frequency (P > 0.05). (5) Comet assay: Comet rate of positive control (5.0 microg/ml methyl methanesulfonate) was 94.5%, higher than that of negative control (7.0%) (P < 0.05), while comet rates in varying concentrations of cefuroxime lactone showed no statistically difference compared with the negative control (P > 0.05). CONCLUSION: genotoxicity was observed under our experimental conditions, which suggested that cefuroxime lactone has no mutagenic effect.

Neutrophil-to-lymphocyte ratio predicts prognosis of patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is one predictive factor for poor prognosis of patients with hepatocellular carcinoma (HCC). In response to contradictory data concerning the predictive ability of NLR, we performed a meta-analysis for the determination of its prognostic value in patients with HCC. METHODS: We systematically searched several databases including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang databases with the updated date of September 21, 2020. Inclusion criteria: RCT studies reporting the prognostic value of the serum levels of NLR in HCC patients receiving treatment were enrolled. Pooled estimates of odds ratio (OR) and diagnostic odds ratio (DOR) were used to assess the prognostic performance of NLR in HCC patients. Overall survival (OS) was the primary outcome and progression-free survival (PFS) was secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Furthermore, risk of bias assessment of included studies is specified by Cochrane Risk Bias Assessment Tool. RESULTS: This analysis included 9 studies containing a total of 3,862 HCC patients. High baseline NLR was significantly correlated with poor prognosis or recurrence. The patient-based analysis of pooled estimates was as follows: sensitivity, 0.68 (95% CI: 0.58-0.77); specificity, 0.73 (95% CI: 0.61-0.82); DOR, 6.347 (95% CI: 5.450-7.391). The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLHR) were 2.5 (95% CI: 1.8-3.6) and 0.43 (95% CI: 0.33-0.57). Furthermore, the area under the curve (AUC) of summary receiver operating characteristic (SROC) reflecting the prognostic accuracy was 0.76 (95% CI: 0.72-0.80). Results obtained from subgroup meta-analyses and overall meta-analyses were accordingly consistent with each other. CONCLUSIONS: Our findings suggested that NLR is an effective prognostic factor for patients with HCC, especially for those from East Asian populations with high incidence. In the future, trials with larger sample sizes and more high-quality evidence are needed to further improve patient outcomes.

Nek2B accelerates the progression of hepatocellular carcinoma through regulating SFRP1 to activate the Wnt/ß-catenin pathway.

PURPOSE: The purpose of this study was to clarify the expression pattern of Nek2B in hepatocellular carcinoma (HCC) and its influence on malignant phenotypes of HCC through regulating SFRP1 and the Wnt/ß-catenin pathway. METHODS: Nek2B levels in 64 paired HCC tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between Nek2B level and clinical parameters of HCC patients was analyzed. Regulatory effects of Nek2B and SFRP1 on clonality, proliferation and apoptosis of MHCC97H and Hep3B cells were determined through functional experiments. Western blot was conducted to detect protein levels of SFRP1, ß-catenin, c-myc, cyclinD1 and MMP7 in HCC cells with overexpression or knockdown of Nek2B. At last, rescue experiments were performed to clarify the role of Nek2B/SFRP1 regulatory loop in aggravating the progression of HCC. RESULTS: Nek2B was upregulated in HCC tissues and cells. HCC patients expressing a high level of Nek2B were in more advanced tumor stage and had worse prognosis. Overexpression of Nek2B in MHCC97H cells enhanced clonality, 5-Ethynyl-2'- deoxyuridine (EdU)-positive ratio and suppressed apoptosis. Besides, knockdown of Nek2B in Hep3B cells yielded the opposite results. SFRP1 was downregulated in HCC, and low level of SFRP1 predicted worse prognosis of HCC. Overexpression of Nek2B downregulated SFRP1, but upregulated ß-catenin, c-myc, cyclinD1 and MMP7 in HCC cells. Importantly, Nek2B/SFRP1 regulatory loop was identified to aggravate the progression of HCC. CONCLUSIONS: Nek2B is upregulated in HCC, and closely linked to tumor stage and poor prognosis in HCC patients. Through interaction with SFRP1, Nek2B aggravates the progression of HCC by activating the Wnt/ß-catenin pathway.

Multiomics Study Reveals Enterococcus and Subdoligranulum Are Beneficial to Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a life-threatening disease for premature infants with low body weight. Due to its fragile gut microbiome and successful treatment of fecal microbiota transplantation (FMT) for intestinal disease, we aimed to reveal the multiple-omics changes after FMT and/or sulperazone treatment. In this study, 2-week-old newborn rabbits were used to simulate the NEC model and grouped into healthy control, NEC, sulperazone treatment, FTM treatment, and FMT and sulperazone combination treatment. We evaluated the intestinal pathology and survival to define the benefit from each treatment and performed microbiome and transcriptome analysis to reveal the changes in microcosmic level, which could be helpful to understand the pathogenesis of NEC and develop new strategy. We found NEC rabbits benefit more from the combination of FMT and sulperazone treatment. Combination treatment reverses a lot of microorganisms dysregulated by NEC and showed the most similar transcript profiler with healthy control. Moreover, a combination of FMT and sulperazone significantly prolonged the survival of NEC rabbits. Function enrichment showed that metabolism and viral life cycle are the most significant changes in NEC. FMT is a common therapy method for NEC. Meanwhile, in the severe situation of NEC with intestinal infection, the first therapy strategy is preferred the third-generation cephalosporin, among which sulperazone is used widely and the effect is remarkable. So, we used sulperazone to treat the rabbits with the NEC. In this research, we aim to explore the different effects on NEC between FMT and sulperazone as well as the combination. Considering the microbiome and transcriptome result, we make a conclusion that the Enterococcus and Subdoligranulum benefits NEC by influencing the bacterial phages and butyrate production, respectively.

A non-invasive model for predicting liver fibrosis in HBeAg-positive patients with normal or slightly elevated alanine aminotransferase.

ABSTRACT: Early and accurate diagnosis of liver fibrosis is necessary for HBeAg-positive chronic hepatitis B (CHB) patients with normal or slightly increased alanine aminotransferase (ALT), Liver biopsy and many non-invasive predicting markers have several application restrictions in grass-roots hospitals. We aimed to construct a non-invasive model based on routinely serum markers to predict liver fibrosis for this population.A total of 363 CHB patients with HBeAg-positive, ALT ≤2-fold the upper limit of normal and liver biopsy data were randomly divided into training (n = 266) and validation groups (n = 97). Two non-invasive models were established based on multivariable logistic regression analysis in the training group. Model 2 with a lower Akaike information criterion (AIC) was selected as a better predictive model. Receiver operating characteristic (ROC) was used to evaluate the model and was then independently validated in the validation group.The formula of Model 2 was logit (Model value) = 5.67+0.08 × Age -2.44 × log10 [the quantification of serum HBsAg (qHBsAg)] -0.60 × log10 [the quantification of serum HBeAg (qHBeAg)]+0.02 × ALT+0.03 ×  aspartate aminotransferase (AST). The area under the ROC curve (AUC) was 0.89 for the training group and 0.86 for the validation group. Using 2 cut-off points of -2.61 and 0.25, 59% of patients could be identified with liver fibrosis and antiviral treatment decisions were made without liver biopsies, and 149 patients were recommended to undergo liver biopsy for accurate diagnosis.In this study, the non-invasive model could predict liver fibrosis and may reduce the need for liver biopsy in HBeAg-positive CHB patients with normal or slightly increased ALT.

Gene Mining and Sequence Analysis of Purine Nucleosidase Based on RNA-Seq.

Caterpillar fungus (Ophiocordyceps sinensis) is one of the most valued fungal Traditional Chinese medicine (TCM), and it contains plenty of active ingredients such as adenosine. Adenosine is considered as a biologically effective ingredient that has a variety of anti-tumor and immunomodulatory activities. In order to further elucidate the mechanism of purine nucleosidase (PN) in adenosine biosynthesis, a gene encoding PN was successfully mined and further analyzed based on the RNA-Seq database of caterpillar fungus. The full-length cDNA of PN was 855 bp, which encoded 284 amino acids. BLAST analysis showed the highest homology of 85.06% with nucleoside hydrolase in NCBI. ProtProm analysis showed that the relative molecular weight was 30.69 kDa and the isoelectric point was 11.55. The secondary structure of PN was predicted by Predict Protein; the results showed that alpha helix structure accounted for 28.17%, strand structure accounted for 11.97%, and loop structure accounted for 59.86%. Moreover, PN gene was further cloned from transcriptome and detected by agarose gel electrophoresis for verification. This study provides more sufficient scientific basis and new ideas for the genetic regulation of adenosine biosynthesis in fungal TCM.

Circulating S100A8/A9 Levels Reflect Intraocular Inflammation in Uveitis Patients.

Purpose: To investigate whether there is an association between circulating S100A8/A9 levels and uveitis activity.Methods: A total of 549 plasma samples were collected from uveitis patients and non-uveitic controls.Results: S100A8/A9 plasma levels were elevated in uveitis patients compared to non-uveitic controls (P < 0.001). S100A8/A9 plasma levels in patients with active acute anterior uveitis (AAU) were significantly elevated and remarkably decreased in parallel with the severity of intraocular inflammation after corticosteroid treatment (P < 0.001). S100A8/A9 plasma levels were also higher in AAU patients with ankylosing spondylitis (AS) than in patients without AS (P = 0.02). S100A8/A9 plasma levels were significantly increased in uveitis patients with elevated C-reactive protein (CRP, P = 0.004) or erythrocyte sedimentation rates (ESR, P = 0.049) levels compared to uveitis patients with normal CRP or ESR values.Conclusion: Circulating S100A8/A9 might be a useful biomarker for the measurement of intraocular inflammation.

Oxidative damage of the extracts of condensate, particulate and semivolatile organic compounds from gasoline engine exhausts on testicles of rats.

Oxidative damage induced by extracts of condensate, particulate matters and semivolatile organic compounds from gasoline engine exhausts were investigated in testicles of adult Sprague-Dawley rats. The results showed that gasoline engine exhaust could increase the contents of malondialdehyde and carbonyl protein, decrease activities of superoxide dismutase and glutathione peroxidase, and induce DNA damage in testicle of rat. Taking together, the gasoline engine exhaust could promote oxidative damage of bio-macromolecular in testicles of rat and oxidative stress might be an alternative mechanism for male reproductive function of male mammals.

[Changes of the life span and certain biochemical indexes on Drosophila melanogaster by ethanol exposure].

OBJECTIVE: To explore the effect of ethanol on the life span and the activities of SOD and GSH-Px as well as the contents of MBA in Drosophila melanogaster. METHODS: Newly trapped and not mated 7200 flies were collected within 8 hours and separated by sex. 2400 flies were selected and randomly divided into six groups (0, 9, 27, 90, 270 and 8l0 mmol/L). Each group contained 400 flies, 200 male flies and 200 female flies. The numbers of dead flies were counted everyday and the culture mediums were replaced every 4 days until all flies died. Another 4800 flies were randomly divided into 4 groups (0, 27, 90 and 270 mmol/L). Each group contained 1200 flies, half male and half female. The activities of SOD and GSH-Px as well as the contents of MBA were detected at the days of 0th, 10th, 20th and 30th after ethanol exposure. Results The life span of Drosophila exposed to high dose ethanol reduced obviously. Activities of SOD and GSH-Px and contents of MDA of Drosophila exposed to ethanol reduced and enhanced with increasing of ethanol doses. And at the same doses (90 mmol/L and 270 mmol/L), activities of SOD and GSH-Px reduced, while contents of MDA elevated with increasing of exposure time. Exposed to high dose of ethanol at the days of 20 or 30, activities of SOD and GSH-Px and contents of MDA in Drosophila reduced and enhanced significantly in comparison with control group. CONCLUSION: Ethanol could reduce the life span and the activities of SOD and GSH-Px, and enhance MBA content of Drosophila.

[Oxidative damage effects of A549 and A549-R cells induced by mainstream smoke].

OBJECTIVE: To explore the effects of oxidative damage induced by mainstream smoke (MS) on A549 and A549-R cells of hOGG1 deficient cell. METHODS: A549 cells and A549-R cells with down-regulated hOGG1 gene were treated at the concentrations of MS for 2h. The cellular sensitivities and DNA damages were measured by MTT assay and comet assay, respectively. The contents of ROS and 8-OHdG in both cells were examined by fluorescence method and HPLC-ECD. RESULTS: The cell viabilities decreased with increases of concentration of MS. The IC50 of hOGG1 deficient A549-R cell was more lower than that in A549 cell (P < 0.05). With dose increases of MS, the contents of ROS increased in both cell lines. When MS was more than or equal to 1.25 No. of cigarette/L, the contents of ROS in A549-R cells were much higher than those in A549 cells. The comet assay indicated that DNA damages of A549-R cells were more higher than those in A549 cells, and comet rate, tail length and OTM in A549-R cells were more higher in comparison with A549 cells (P < 0.05) at the levers of all concentrations. Furthermore, the levels of 8-OHdG in A549-R cells were higher than those of A549 cells at the doses of 2.5 and 5 No. of cigarette/L (P < 0.05). CONCLUSION: Mainstream smoke could induce oxidative damage in A549 and A549-R cells and hOGG1 deficiency cell could increase sensitivity to MS.

Elevated Plasma Levels of Drebrin in Glaucoma Patients With Neurodegeneration.

Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Aberrations in several cytoskeletal proteins, such as tau have been implicated in the pathogenesis of neurodegenerative diseases, could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Developmentally regulated brain protein (Drebrin or DBN1) is an evolutionarily conserved actin-binding protein playing a prominent role in neurons and is implicated in neurodegenerative diseases. However, the relationship between circulating DBN1 levels and RGC degeneration in glaucoma patients remains unclear. In our preliminary study, we detected drebrin protein in the plasma of glaucoma patients using proteomic analysis. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels. We observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonaxonopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients, elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, we conducted experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC. This result reinforces the potentiality of circulating DBN1 levels are increased in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may be a useful indicator for monitoring progression of neurodegenerative diseases.