Autoantibodies to NR2A Peptide of the Glutamate/NMDA Receptor in Patients with Seizure Disorders in Neuropsychiatric Systemic Lupus Erythematosus.

Objective. Seizure disorders are one of the most disabling, life-threatening, and the least understood syndromes associated with neuropsychiatric SLE (NPSLE). N-Methyl-D-aspartate (NMDA) receptors are a subgroup of the glutamate receptor family, whose NR2A subunit was found on neuronal cells (anti-NR2A) in NPSLE patients with different types of epilepsy. The present study was conducted to determine the serum levels of anti-NR2A antibodies in a large group of SLE patients, to investigate the possible correlation between the presence of the NR2A specific antibodies and NPSLE-related seizure disorders. Methods and Results. The study population consisted of 107 SLE patients and 43 age- and sex-matched healthy controls. 73 SLE patients had active disease. 36 of these had NPSLE. NMDA levels were measured by ELISA. Clinical and serological parameters were assessed according to routine procedures. The levels of anti-NR2A antibodies were significantly higher in NPSLE patients, compared with non-NPSLE patients and healthy controls. Furthermore, the levels of NPSLE in patients with seizure disorders were shown to be higher than in those with cognitive dysfunction and other CNS symptoms, however, without significance. Increase in serum anti-NR2A antibodies levels correlated to anti-dsDNA antibody and SLEDAI as well as complement levels. Conclusion. We suggest that anti-NR2A antibodies play a role in the pathogenesis of NPSLE with seizure disorders.

[Study on arsenic speciation changes in crude and processed traditional Chinese medicines by HPLC-ICP-MS].

A HPLC-ICP-MS method for simultaneous determination of As(III), As(V), MMA and DMA in traditional Chinese medicines (TCMs) was established, and the contents of As(III), As(V), MMA and DMA in a TCM with high total arsenic content (Cordyceps) and 5 crude and processed TCMs (Radix Astragali, Radix et Rhizoma Rhei, Radix Scutellariae, Radix Polygoni Multiflori and Radix Rehmanniae) were determined and analyzed. The method validation indicated that the correlative coefficients (r) for all speciations were bigger than 0.9984; the limits of quantitation (LOQ) were from 0.8 to 1.0 microg x L(-1); the reproducibility and stability were satisfactory with all RSDs less than 10%; the spiked recoveries ranged from 82.40% to 119.5%. The results of samples analysis showed that the inorganic arsenic (As(III) and As(V)) was the dominating speciation in the tested TCMs; MMA and DMA were not found in all plant resourced TCMs, but MMA was found in Cordyceps; all the tested TCMs indicated a content increasing of inorganic arsenic after processing.

The Metabolic Reprogramming Profiles in the Liver Fibrosis of Mice Infected with Schistosoma japonicum.

Disordered glucose and lipid metabolism contributes to the progression of several liver diseases, while the upregulation of phosphatase and tensin homology deleted on chromosome ten (PTEN), a well-known tumour suppressor gene, can improve the condition through metabolic programming. This study first characterized the metabolic profiles and the involvement of PTEN in the hepatic fibrosis induced by Schistosoma japonicum (S. japonicum) to provide a novel clue for metabolism-targeted treatment. Compared with control mice, infected mice showed infiltrated immune cells in their livers, increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased glucose levels in their sera. The expression of key enzymes in the glycolytic pathway was significantly increased, and the expression of gluconeogenic genes was distinctly decreased. Moreover, the infection upregulated the hepatic expression of enzymes involved in fatty acid oxidation, which was consistent with the decreased number of lipid droplets in livers and the lowered levels of triglyceride in sera. Consistently, PTEN and its downstream signalling were significantly inhibited. In vitro, soluble egg antigen (SEA) downregulated the expression of PTEN in both the macrophage RAW264.7 cell line and the murine hepatocellular carcinoma HEP1-6 cell line, and induced a metabolic phenotype similar to the in vivo results. Overall, this study showed that S. japonicum infection induced the reprogramming of glucose and lipid metabolism in mice during the period of liver fibrosis and that SEA could act as a modulator to trigger such a metabolic switch in macrophages and hepatocytes. PTEN might play an essential role in mediating these metabolic reprogramming events.

Suspiciousness in young minds: Convergent evidence from non-clinical, clinical and community twin samples.

BACKGROUND: We validated the Social Mistrust Scale (SMS) and utilized it to examine the structure, prevalence, and heritability of social mistrust in a large sample of Chinese children and adolescents. METHODS: In Study 1, a large sample of healthy twins (N=2094) aged 8 to 14years (M=10.27years, SD=2) completed the SMS. Structural equation modeling (SEM) was conducted to assess the structure of the SMS and to estimate the heritability of social mistrust in a sub-sample of twins (n=756 pairs). In Study 2, 32 adolescents with childhood-onset schizophrenia were compared with 34 healthy controls on levels of suspiciousness and clinical symptoms to examine the associations between the SMS and the Positive and Negative Syndrome Scale (PANSS). RESULTS: We found a three-factor structure for social mistrust (home, school, and general mistrust). Social mistrust was found to be moderately - heritable (19%-40%), with mistrust at home most strongly influenced by genetic factors. Compared with 11.76% of the healthy controls, 56.25% of the adolescents with early-onset schizophrenia exhibited very high levels of social mistrust on all three subscales of the SMS. The SMS exhibited good discriminant validity in distinguishing adolescents with childhood-onset schizophrenia from healthy controls and showed associations with a broad range of symptoms assessed by the PANSS. CONCLUSIONS: Social mistrust assessed by the SMS may be heritable. The SMS demonstrates good discriminant validity with clinical diagnoses of schizophrenia. However, it seems to be correlated with multiple aspects of psychopathology in the schizophrenia group, rather than being specific to delusional ideation/paranoia.

Complete mitochondrial genome sequence and mutations of the Lung cancer model inbred athymic Rowett nude rat strain.

In the present work, we undertook the complete mitochondrial genome sequencing of an important Lung cancer model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one non-coding control region (D-loop region). The mutation events were also reported.

Relationships between behavioral symptoms of non-medicated Chinese children with attention deficit hyperactivity disorder and parenting stress: Comparison of different subtypes and comorbidities.

INTRODUCTION: To identify the characteristics of behavior problems among children with attention deficit hyperactivity disorder (ADHD) and their relation with parenting stress. METHODS: The Conners Parent Symptom Questionnaire (PSQ) and Parenting Stress Index (PSI) were used to assess the symptoms and parenting stress of 132 non-medicated children with ADHD as compared with 88 healthy controls. RESULTS: Every PSQ factor of ADHD children was higher than in the control group; children with the combined subtype of ADHD had the highest scores in conduct and learning problems, impulsivity/hyperactivity, and overall hyperactivity index; the PSI total stress, child domain, and parent domain scores were all higher in the ADHD group than in the control group; children with the combined subtype of ADHD had the highest score in the competence subscale of the parent domain, whereas the PSI total stress score of parents of children with ADHD and comorbid oppositional defiant disorder (ODD) was higher than that of parents of children with only ADHD. The PSI total stress score was positively correlated with all PSQ factor scores. The PSQ factors of conduct problems and learning problems were found to be significant predictors in a regression analysis. DISCUSSION: The children with ADHD exhibited abnormal parenting stress compared with healthy controls, which was much more pronounced when the children had comorbid ODD. Furthermore, parenting stress was related with the severity of ADHD symptoms, suggesting that children with the combined subtype of ADHD require particular attention in the future.

Comparison of psychological symptoms and serum levels of neurotransmitters in Shanghai adolescents with and without internet addiction disorder: a case-control study.

BACKGROUND: Internet addiction disorder (IAD) is now recognized internationally and is known to be linked with academic and social impairment. To date, we know little about its associated main biological factors. This study aimed to collect a carefully defined group of adolescents with IAD and an age- and gender-matched typically developing comparison group. We hypothesized that the young people with IAD would have higher rates of self-reported anxiety and depressive symptoms, have altered levels of peripheral blood dopamine, norepinephrine and serotonin. In addition, we hypothesized the hours spent online are correlated with the severity of depression and anxiety among these young people with IAD. METHODOLOGY/PRINCIPAL FINDING: A cross-sectional study of 20 adolescents who met Beard's criteria for IAD and 15 typically developing adolescents (comparison group) was conducted. All the participants completed the Self Rating Depression Scale (SDS), Self Rating Anxiety Scale (SAS), and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Peripheral blood dopamine, serotonin and norepinephrine were assayed. The mean level of norepinephrine was lower in the IAD group than that in the typically developing participants, while dopamine and serotonin levels did not differ. The SDS, SAS and SCARED symptom scores were increased in the adolescents with IAD. A logistic regression analysis revealed that a higher SAS score and lower level of norepinephrine independently predicted IAD group membership. There was no significant correlation between hours spent online and scores of SAS/SDS in IAD group. CONCLUSIONS/SIGNIFICANCE: Increased self-reported anxiety and lower peripheral blood norepinephrine are independently associated with IAD.

Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases.

IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as α-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.