Autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations: a report of 8 cases and literature review / 中国当代儿科杂志

OBJECTIVES@#To summarize the clinical phenotype and genetic characteristics of children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations.@*METHODS@#A retrospective analysis was performed on the medical data of 8 children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University.@*RESULTS@#The mean age of onset was 9 months for the 8 children. All children had moderate-to-severe developmental delay (especially delayed language development), among whom 7 children also had seizures. Among these 8 children, 7 had novel heterozygous mutations (3 with frameshift mutations, 2 with nonsense mutations, and 2 with missense mutations) and 1 had 6p21.3 microdeletion. According to the literature review, there were 48 Chinese children with mental retardation caused by SYNGAP1 gene mutations (including the children in this study), among whom 40 had seizures, and the mean age of onset of seizures was 31.4 months. Frameshift mutations (15/48, 31%) and nonsense mutations (19/48, 40%) were relatively common in these children. In terms of treatment, among the 33 children with a history of epileptic medication, 28 (28/33, 85%) showed response to valproic acid antiepileptic treatment and 16 (16/33, 48%) achieved complete seizure control after valproic acid monotherapy or combined therapy.@*CONCLUSIONS@#Children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations tend to have an early age of onset, and most of them are accompanied by seizures. These children mainly have frameshift and nonsense mutations. Valproic acid is effective for the treatment of seizures in most children.

Effect of Bergapten on Apoptosis of HepG2 and Hep3B Cells Through PI3K/Akt Pathway / 中国实验方剂学杂志

Objective::To investigate the effect of bergapten on the apoptosis of HepG2 and Hep3B cells through phosphatidylinositol 3 kinase (PI3K)/protein kinase B(Akt) pathway. Method::Bergamot (5, 50, 200 μmol·L-1) groups and blank group were set up. The effect of bergapten at different concentrations on proliferation of HepG2 and Hep3B cells for 24, 48 h were detected by thiazolyl blue(MTT) assay. Apoptosis was detected by Annexin V-FITC/propidium iodide double staining. Quantitative real-time fluorescence reverse transcriptional polymerase chain reaction (Real-time PCR) and Western blot assay were used to detect relevant mRNA and proteins expressions. The clone formation rate and the effect of HepG2 and Hep3B cells in each group were evaluated by plate cell clone formation. Result::MTT assay showed that bergapten could significantly inhibit the proliferation activity of HepG2 and Hep3B cells in a time-dependent manner. Flow cytometry analysis showed that bergapten in 200 μmol·L-1 concentration groups had significant pro-apoptotic effect on HepG2 and Hep3B cells after 48 h (P<0.05). Western blot results showed that bergamolactone could up-regulate the protein expressions of Caspase-3, Caspase-8 (P<0.05), and down-regulate protein expressions of B-lymphocytoma-2 (Bcl-2), PI3K (P<0.05). Real-time PCR results showed that mRNA expressions of PI3K and Akt were decreased(P<0.05). The results of plate cell clone formation experiment showed that with the increase of the concentration of bergamolide, the cell clone formation rate of each group showed a decreasing trend, particularly in 200 μmol·L-1 concentration group (P<0.05). Conclusion::Bergapten can inhibit the proliferation of HepG2 and Hep3B cells, which may be induced through the PI3K/Akt signaling pathway.

FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in a O⁶-methylguanine-DNA methyltransferase-dependent manner

Glioma is the most common brain tumor with a dismal prognosis. While temozolomide (TMZ) based chemotherapy significantly improves survival in glioma patients, resistance against this compound commonly leads to glioma treatment failure. Overexpression of long-noncoding RNA (LncRNA) FoxD2 adjacent opposite strand RNA 1 (FoxD2-AS1) was identified to promote glioma development, but the role in TMZ resistance remains unclear. In this paper, we found that FoxD2-AS1 was overexpressed in recurrent glioma, high FoxD2-AS1 expression was significantly correlated with poor patient outcome. Methylation of O⁶-methylguanine-DNA methyltransferase (MGMT) is significantly less frequent in high FoxD2-AS1 expression patients. Knockdown of FoxD2-AS1 decreased the proliferation, metastatic ability of glioma cells and promote the sensitivity to TMZ in glioma cells. Furthermore, knockdown of FoxD2-AS1 induced hypermethylation of the promoter region of MGMT. Our data suggested that FoxD2-AS1 is a clinical relevance LncRNA and mediates TMZ resistance by regulating the methylation status of the MGMT promoter region.

Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes

Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with 50 µM curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%–8.05% to 27.63%–35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by 50 µM curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the editosome in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

Analysis of GCH1 gene mutation of close relatives marriage caused dopa reactive dystonia ( report of one family) / 临床神经病学杂志

Objective To analyze the characteristics of GCH1 gene mutation of close relatives marriage caused dopa reactive dystonia (DRD).Methods The data of 3 patients with DRD from the same family in our hospital and their families were analyzed.Genes related to hereditary dyskinesia in their families were detected and validated. Results In this family, the proband’s parents (Ⅲ3 and Ⅲ4) were close relatives.The proband (Ⅳ2) and her eldest daughter (Ⅴ2) and niece (Ⅴ7) were all DRD patients.All of them were young onset , mainly manifested as Parkinsonina-like symptoms and dystonia , and all responded well to dopamine therapy.Gene detection showed that the GCH1 gene had c.245T＞C (p.Leu82Pro) mutation.The second daughter (Ⅴ3), son (Ⅴ5), granddaughter (Ⅵ3) and brother (Ⅳ3) of the proband were carriers of abnormal genes.Conclusions Close relatives marriage increases the incidence of DRD.DRD may be considered in patients with a positive family history of dystonia.Gene detection is an effective diagnosis method.

Effects of squalene on expression of LDLR in HepG2 cells and its mechanism / 中国药理学通报

Aim To investigate the effect of squalene on LDLR expression in HepG2 cells and its mechanism of down-regulated cholesterol. Methods The prolifer-ation of HepG2 cells exposed to squalene at different concentrations was measured by MTT assay. The effect of squalene on the expression of LDLR in HepG2 cells was measured by flow cytometry and fluorescence mi-croscopy. The effect of different concentrations of squa-lene on the interaction between SCAP and Insig2, two key protein molecules of SREBP pathway, was assayed by FRET technology. Results MTT results showed that squalene had inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner. Flow cy-tometry and fluorescence microscopy results showed that squalene enhanced LDLR expression in HepG2 cells compared with the control group. The results of FRET technology revealed that compared with model control group, the YFP fluorescence value in Squalene group dramatically declined, and the YFP fluorescence value of each drug group decreased with the range of 5~25 μmol·L-1 squalene concentration. Conclusions Squalene may promote the expression of LDLR in HepG2 cells through inhibiting the interaction between SCAP and Insig2 proteins in SREBP pathway, which may confirm that squalene is a potential novel drug for the down-regulation of cholesterol level.

Analysis of alternative splicing pattern of ADAR2 pre-mRNA in human glioma cell lines / 中国肿瘤临床

Objective:This study aims to analyze the differences in the alternative splicing pattern of ADAR2 among glioma cell lines U87, U251, A172, and normal human astrocyte HA1800. Methods:A-to-I editing level at the Q/R-Site of GluR-2 was analyzed by RT-PCR and sequencing. Real-time PCR was performed to detect the expression level of each alternatively splicing variant using a specific primer that was confirmed to amplify only the targeted template and not other alternatively spliced variant fragments. Results:We verified that the Q/R-Site of GluR-2 is under-edited in glioma cell lines. Real-time PCR revealed that the ADAR2 pre-mRNA splic-ing pattern has no significant difference at exons 1a and 2 between glioma cell lines and normal human astrocyte. We also detected that the amount of alternative splicing variants, including exon 5a, was higher than that of alternative splicing variants not including exon 5a in human glioma cell lines. However, the expression of alternative splicing variants, including exon 5a, was lower than that of alterna-tive splicing variants not including exon 5a in human astrocyte. Conclusion:Evident differences in splicing were observed at the site of exon 5a between glioma cell lines and normal human astrocytes. The difference in the alternatively splicing pattern at exon 5a may be attributed to the decreased activity of ADAR2.

Research Progress on the Relationship between miRNAs and Common Liver Diseases / 浙江中医药大学学报

[Obiective] To summarize the research development of the relationship between the occurrence and development of common liver diseases and miRNAs by reading and analysing the literature published in recent 10 years. [Method] By literature retrieval, we consult the literature about miRNA and the clinical research of relevant liver diseases since 2003 and summarize the regulatory mechanism of miRNAs in liver diseases. [Result] miRNAs regulate the expression of target genes at the post-transcriptional level, and they are involved in many important biological processes. In recent years, we can find that miRNAs take part in the regulation of many liver disease-related genes, and the expression level in hepatocellular carcinoma, viral hepatitis, liver fibro-sis, cirrhosis, alcoholic and non-alcoholic fatty liver change in different levels. Part of the regulatory mechanism of miRNAs has been clearly identified, suggesting that miRNAs wil be used as new therapeutic targets for liver diseases. [Conclusion] The regulatory mechanisms of miRNAs in liver diseases make a big difference for the prevention and treatment of liver diseases. These findings provide some novel thoughts about the detection, study and treat-ment about relevant liver diseases. However, many questions are stil vague and unknown, such as the net of its expression and regulation, its biological functions, and the relationship with liver diseases, and al of them are needed to get further attention.

Protective effects of glucagon-like peptide 2 on intestinal ischemia/reperfusion injury in mice / 中国应用生理学杂志

<p><b>AIM</b>To investigate the protective effects of glucagon-like peptide 2(GLP-2) on intestinal ischemia/reperfusion (I/R) injury in mice.</p><p><b>METHODS</b>Intestinal ischemia/reperfusion model in mice were set up and 32 mice of Kunming species were divided randomly into 4 groups (n=8): Sham group, I/R group, I/R + GLP-2 group and I/R + glutamine group. The morphologic changes of intestinal mucosa were observed under LM. The villus height and crypt depth of intestine, the activity of diamine oxidase (DAO) in intestine and bacterial translocation rates of mesenteric lymph nodes (MLN) were detected.</p><p><b>RESULTS</b>Compared with sham operation group, the intestinal villi were sloughed in I/R group with decreased villus height and crypt depth (P < 0.01), the DAO activities were decreased (P < 0.01), and MLN bacterial translocation rates were increased (P < 0.05). While GLP-2 administration improved the villus damage, increased DAO activity (P < 0.01), and decreased MLN bacterial translocation rates (P < 0.05), compared with I/R group.</p><p><b>CONCLUSION</b>GLP-2 have protective effects on intestinal morphology and barrier function after ischemia/reperfusion injury in mice.</p>

Effects of vagotomy on UCP2 mRNA expression and gastric acid secretion in rats / 中国应用生理学杂志

<p><b>AIM</b>The relationship between gastric acid secretion and ATP level, and regulation of uncoupling protein 2 (UCP2) mRNA expression by vagus nerve were studied in vagotomies rats.</p><p><b>METHODS</b>With the high selective vagotomy model, the gastric acidity was titrated to pH 7.0 with 0.1 mol/L NaOH solution and ATP contents were quantified by using fluorimetry. The expression of UCP2 mRNA was observed by using Northern blot in stomach of rats.</p><p><b>RESULTS</b>Both of gastric acidity and ATP contents in stomach body decreased significantly at 24 h after vagotomy. The expression of UCP2 mRNA was markedly increased as compared with sham operation group.</p><p><b>CONCLUSION</b>ATP contents decreased and vagus nerve down-regulates expression of UCP2 mRNA in stomach corpus in vagotomies rats. The results indicates that vagus nerve could underlay the gastric acidity by inhibiting expression of UCP2 mRNA and increasing ATP contents in rats.</p>