BDNF promotes human neural stem cell growth via GSK-3ß-mediated crosstalk with the wnt/ß-catenin signaling pathway.

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/ß-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3ß expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and ß-catenin components were all downregulated, whereas GSK-3ß was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3'-oxime (BIO), a small molecule inhibitor of GSK-3ß. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/ß-catenin signaling pathway, and that this interaction may be mediated by GSK-3ß.

Intestinal flora alterations in patients with ulcerative colitis and their association with inflammation.

Ulcerative colitis (UC), which is a type of inflammatory bowel disease, is a chronic intestinal disorder of multifactorial etiology. Numerous studies have indicated an association between UC and intestinal bacteria. However, a limited number of studies regarding the expression of interleukin-17 (IL-17) and interleukin-23 (IL-23) in association with intestinal bacteria have been performed. The aim of the current study was to investigate the gut microbiota alterations in patients with UC, at a number of taxonomic levels, and their relationship with intestinal inflammation by analyzing the protein expression of IL-17 and IL-23. Specimens were collected from 10 healthy controls and 16 patients with UC. A histological examination was performed in colonic tissues, IL-17 and IL-23 protein expression was detected by immunohistochemistry, fecal samples were sequenced using 16S rDNA sequencing and bioinformatics analysis was performed. The UC group exhibited an increased histological score (P<0.01) and upregulated IL-17 and IL-23 expression (P<0.01). At the order level, the bacterial diversity of the UC group was decreased. ß-diversity analyses, including principal component analysis, principal coordinate analysis and non-metric multidimensional scaling, demonstrated that the two groups of samples were separated into two taxonomic categories, as distinct variations were observed in the analysis of group differences (P=0.001). Regarding the differences in species composition between the groups, Enterococcus was indicated to be the species with the greatest difference in abundance compared with the healthy control group (P<0.01), followed by Lactobacillus (P<0.05), Escherichia-Shigella (P<0.05), Bifidobacterium and Bacteroides. In addition, the average optical density of IL-17 was positively correlated with the histological score (ρ=0.669; P=0.035), Enterococcus (r=0.843; P<0.001), Lactobacillus (r=0.737; P=0.001), Bifidobacterium (r=0.773; P<0.001) and Escherichia-Shigella (r=0.663; P=0.005), and the average optical density of IL-23 was positively correlated with the histological score (ρ=0.733; P=0.016), Enterococcus (r=0.771; P<0.001), Lactobacillus (r=0.566; P=0.022), Bifidobacterium (r=0.517; P=0.041) and Escherichia-Shigella (r=0.613; P=0.012). The results of the present study indicated that the intestinal microbiota of patients with UC differed from that of healthy controls at multiple taxonomic levels. The alterations of the intestinal microflora were closely associated with the degree of inflammation. The IL-23/IL-17 axis, as a key factor in the development of UC, maybe associated with the alterations of intestinal microflora. The interaction between intestinal microflora and the IL-23/IL-17 axis may serve an important role in the pathogenesis of UC.

Carbapenem-Resistant Enterobacter hormaechei ST1103 with IMP-26 Carbapenemase and ESBL Gene bla SHV-178.

PURPOSE: To investigate the occurrence and genetic characteristics of the bla IMP-26-positive plasmid from a multidrug-resistant clinical isolate, Enterobacter hormaechei L51. METHODS: Species identification was determined by MALDI-TOF MS and Sanger sequencing. Antimicrobial susceptibility testing was performed by the agar dilution and broth microdilution. Whole-genome sequencing was conducted using Illumina HiSeq 4000-PE150 and PacBio Sequel platforms, and the genome was annotated by the RAST annotation server. The ANI analysis of genomes was performed using OAT. Phylogenetic reconstruction and analyses were performed using the Harvest suite based on the core-genome SNPs of 61 publicly available E. hormaechei genomes. RESULTS: The E. hormaechei L51 genome consists of a 5,018,729 bp circular chromosome and a 343,918 bp conjugative IncHI2/2A plasmid pEHZJ1 encoding bla IMP-26 which surrounding genetic context was intI1-bla IMP-26-ltrA-qacE∆1-sul1. A new sequence type (ST1103) was assigned for the isolate L51 which was resistant to cephalosporins, carbapenems, but sensitive to piperacillin-tazobactam, amikacin, tigecycline, trimethoprim-sulfamethoxazole and colistin. Phylogenetic analysis demonstrated that E. hormaechei L51 belonged to the same subspecies as the reference strain E. hormaechei SCEH020042, however 18,248 divergent SNP were identified. Resistance genes in pEHZJ1 including aac(3)-IIc, aac(6') -IIc, bla SHV-178, bla DHA-1, bla TEM-1, bla IMP-26, ereA2, catII, fosA5, qnrB4, tet(D), sul1 and dfrA19. CONCLUSION: In our study, we identified a conjugative IncHI2/2A plasmid carrying bla IMP-26 and bla SHV-178 in E. hormaechei ST1103, a novel multidrug-resistant strain isolated from China, and describe the underlying resistance mechanisms of the strain and detailed genetic context of mega plasmid pEHZJ1.

miR­378a­3p inhibits cellular proliferation and migration in glioblastoma multiforme by targeting tetraspanin 17.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor and patients with this disease tend to have poor clinical outcome. MicroRNAs (miRs) are important regulators of a number of key pathways implicated in tumor pathogenesis. Recently, the expression of miR­378 was shown to be dysregulated in several different types of cancer, including gastric cancer, colorectal cancer and oral carcinoma. Additional studies have demonstrated that miR­378 may serve as a potential therapeutic target against human breast cancer. However, the underlying mechanisms and potential targets of miR­378a­3p involved in GBM remain unknown. The aim of the present of was to determine the effects of miR­378a­3p and its potential targets. Tetraspanin 17 (TSPAN17) is involved in the neoplastic events in GBM and is a member of the tetraspanin family of proteins. The tetraspanins are involved in the regulation of cell growth, migration and invasion of several different types of cancer cell lines, and may potentially act as an oncogene associated with GBM pathology. The results of the present study showed that high miR­378a­3p and low TSPAN17 expression levels were associated with improved survival in patients with GBM. Additionally, high levels of TSPAN17 were linked to the poor prognosis of patients with GBM aged 50­60, larger tumor sizes (≥5 cm) and an advanced World Health Organization stage. TSPAN17 was identified and confirmed as a direct target of miR­378a­3p using a luciferase reporter assay in human glioma cell lines. Overexpression of miR­378a­3p in either of U87MG or MT­330 cells decreased the expression of TSPAN17, promoted apoptosis and decreased proliferation, migration and invasion. Overexpression of TSPAN17 attenuated the aforementioned effects induced by miR­378a­3p overexpression. The present study indicated that miR­378a­3p suppresses the progression of GBM by reducing TSPAN17 expression, and may thus serve as a potential therapeutic target for treating patients with GBM.

Prevalence of major depressive disorder and socio-demographic correlates: Results of a representative household epidemiological survey in Beijing, China.

BACKGROUND: Major depressive disorder (MDD) is the most prevalent mental disorder in the general population and has been associated with socioeconomic factors. Beijing has undergone significant socioeconomic changes in last decade, however no large-scale community epidemiological surveys of MDD have been conducted in Beijing since 2003. AIMS: To determine the prevalence of MDD and its socio-demographic correlates in a representative household sample of the general population in Beijing, China. METHOD: Data were collected from the 2010 representative household epidemiological survey of mental disorders in Beijing. The multistage cluster random sampling method was used to select qualified subjects in 18 districts and counties, and then face-to-face interviews were administered using the Chinese version of Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P) during November 1, 2010 to December 31, 2010. RESULTS: 19,874 registered permanent residents were randomly identified and 16,032 (response rate=80.7%) completed face-to-face interviews. The time-point and life-time prevalence rates of MDD were estimated to be 1.10% (95% CI: 0.94-1.26%) and 3.56% (95% CI: 3.27-3.85%) respectively. Significant differences were found in sex, age, location of residence, marital status, education, employment status, personal/family monthly income, perception of family environment and relationship with others, when comparing residents with MDD to those without MDD. Those who were female, aged 45 or above, reported low family income, or reported an "average" or "poor" family environment were associated with a higher risk of MDD. CONCLUSIONS: The prevalence of MDD reported in this survey is relatively lower than that in other western countries. Female sex, age older than 45, low family income, and poor family environment appear to be independent risk factors for MDD.