ARID3B Directly Regulates Ovarian Cancer Promoting Genes

The DNA-binding protein AT-Rich Interactive Domain 3B (ARID3B) is elevated in ovarian cancer and increases tumor growth in a xenograft model of ovarian cancer. However, relatively little is known about ARID3B''s function. In this study we perform the first genome wide screen for ARID3B direct target genes and ARID3B regulated pathways. We identified and confirmed numerous ARID3B target genes by chromatin immunoprecipitation (ChIP) followed by microarray and quantitative RT-PCR. Using motif-finding algorithms, we characterized a binding site for ARID3B, which is similar to the previously known site for the ARID3B paralogue ARID3A. Functionality of this predicted site was demonstrated by ChIP analysis. We next demonstrated that ARID3B induces expression of its targets in ovarian cancer cell lines. We validated that ARID3B binds to an epidermal growth factor receptor (EGFR) enhancer and increases mRNA expression. ARID3B also binds to the promoter of Wnt5A and its receptor FZD5. FZD5 is highly expressed in ovarian cancer cell lines, and is upregulated by exogenous ARID3B. Both ARID3B and FZD5 expression increase adhesion to extracellular matrix (ECM) components including collagen IV, fibronectin and vitronectin. ARID3B-increased adhesion to collagens II and IV require FZD5. This study directly demonstrates that ARID3B binds target genes in a sequence-specific manner, resulting in increased gene expression. Furthermore, our data indicate that ARID3B regulation of direct target genes in the Wnt pathway promotes adhesion of ovarian cancer cells.     

Association between cyclooxygenase-2 gene polymorphisms and risk of periodontitis: a meta-analysis involving 5653 individuals

There ?765G > C, ?1195G > A, and 8473T > C polymorphisms in cyclooxygenase-2 (COX-2) gene polymorphisms and periodontitis risk were investigated based on published studies; however, their results could not give a conclusive result. Hence, we performed this meta-analysis of six published studies with eight case–control studies including these three polymorphisms which searched from PubMed and Web of Science up to October 15th, 2013. Odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between the three polymorphisms of COX-2 and periodontitis risk. The results from 2,580 periodontitis patients and 3,073 healthy controls showed that none of ?765G > C, ?1195G > A, or 8473T > C polymorphism was not associated with periodontitis susceptibility [Take ?765G > C for example: OR = 0.94, 95 % CI = (0.57–1.53) for C vs. G; OR = 2.34, 95 % CI = (0.72–7.62) for CC vs. GG; OR = 0.68, 95 % CI = (0.46–1.01) for CG vs. GG; OR = 0.81, 95 % CI = (0.52–1.27) for (CG+GG) vs. GG; OR = 2.57, 95 % CI = (0.80–8.29) for CC vs. (GG+CG)]. In subgroup analyses according to the type of periodontitis and ethnicity for ?765G > C and ?1195G > A, and deviations in Hardy–Weinberg equilibrium for ?765G > C, we only observe a boundary association between ?1195G > A polymorphism and Asian population. However, due to limitations of this meta-analysis, the results should treat with caution and we suggest the further researches should be carried out to verify our results.     

Antibacterial Activity,Cytotoxicity and Mechanisms of action of Cathelicidin Peptides against Enteric Pathogens in Weaning Piglets

In the last few decades, long-term and high-dose usage of antibiotics in livestock diets has led to the emergence of antibiotic resistant bacteria, antibiotic residues in animal products and environmental pollution, adversely affecting animal health. Because of these concerns, a study screening cathelicidin peptides from different animal origins (i.e. protegrin-1 [PG-1], PMAP-23, LL-37, indolicidin and cathelicidin-BF [C-BF]) as antibiotic replacements with higher antimicrobial activity and lower cytotoxicity was designed to study their mechanisms towards enteric pathogens in weaning piglets. PG-1 and C-BF proved to be the most effective bacteriocids with the widest spectra of activity, with the MIC values equal to or lower than commonly used antibiotics towards several Escherichia and Salmonella strains, and showed a synergistic effect with aureomycin. Mechanism studies suggested the C-BF killing mechanism is based on membrane permeability, while multiple targets maybe exist for PG-1, including membrane and intracellular biomacromolecules. Cytotoxicity tests showed PMAP-23 and C-BF exhibited the lowest cytotoxic effects, while PG-1, LL-37 and indolicidin displayed cytotoxicity by dose. This study demonstrated that among the peptides tested, C-BF has the capacity to inactivate enteric pathogens with lower cytotoxicity and is potentially a novel anti-bacterial agent. The activity of PG-1 is highly efficient, with the potential to reduce cytotoxicity using molecular design.     

Aggravation Effect of Isoflurane on Aβ25–35-Induced Apoptosis and Tau Hyperphosphorylation in PC12 Cells

Some anesthetics have been suggested to induce Alzheimer??s disease (AD) neuro-pathogenesis. Increasing evidence indicates that hyperphosphorylated tau plays a key role in the pathogenic events that occur in AD. Isoflurane has been shown to induce apoptosis, which leads to accumulation of amyloid-?? (A??). We set out to investigate whether isoflurane can induce apoptosis by increasing hyperphosphorylated tau in A??_25?C35-induced cells and the underlying mechanism. Cultured rat pheochromocytoma cells (PC12) were exposed to 20?mM A??_25?C35 alone or with 2?% isoflurane for 6?h. The cell viability was determined by MTT assay, and the apoptosis rate was detected by flowcytometry. Western blotting and immunocytochemical staining were performed to observe the protein expression of Bcl-2 family, tau phosphorylation of different sites, tau protein kinases and phosphatases. Additionally, lithium chloride was administered to all above groups to investigate the changes of apoptosis rate and protein expression. The apoptosis rate was significantly increased in A??_25?C35 group compared with the others groups, which was accompanied by bcl-2 decline, and the phosphorylation of glycogen synthase kinase-3??(GSK-3??) and tau of two sites increased. LiCl attenuated the cellular apoptosis by inhibition the level of tau phosphorylation. Isoflurane upregulated the level of phosphorylated GSK-3??, which phosphorylate tau at different sites, and aggravated the apoptotic rate of the A??_25?C35-induced PC12 cells. It indicated that isoflurane-induced tau phosphorylation might play a role in the AD-like development.     

AMPK regulates homeostasis of invasion and viability in trophoblasts by redirecting glucose metabolism: Implications for pre‐eclampsia

Pre‐eclampsia (PE) is deemed an ischemia‐induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography–mass spectrometry (GC–MS). Trophoblast‐specific AMPKα1‐deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle‐delivered A769662. Trophoblast glucose uptake was measured by 2‐NBDG and 2‐deoxy‐d‐[³H] glucose uptake assays. Cellular metabolism was investigated by the Seahorse assay and GC–MS.PE complicated trophoblasts are associated with AMPK hyperactivation due not to energy deficiency. Thereafter, AMPK activation during placentation exacerbated PE manifestations but alleviated cell death in the placenta. AMPK activation in trophoblasts contributed to GLUT3 translocation and subsequent glucose metabolism, which were redirected into gluconeogenesis, resulting in deposition of glycogen and accumulation of phosphoenolpyruvate; the latter enhanced viability but compromised trophoblast invasion. However, ablation of AMPK in the mouse placenta resulted in decreased glycogen deposition and structural malformation. These data reveal a novel homeostasis between invasiveness and viability in trophoblasts, which is mechanistically relevant for switching between the ‘go’ and ‘grow’ cellular programs.

Pre‐eclampsia (PE) is associated with trophoblast AMPK hyperactivation, presumably due to LKB1 phosphorylation, and glucose uptake is consequently increased via trafficking of GLUT3 from the cytosol to the plasma membrane. Such translocation enhances glycolytic flux and redirects glucose metabolic intermediates into gluconeogenesis, resulting in PEP accumulation, which not only benefits cell survival but also suppresses invasion by repressing MMPs, and thus in turn modulates switching between the ‘go’ and ‘grow’ cellular programs.     

中国二种盗蛛的分类研究(蜘蛛目:盗蛛科)

本文对我国两种盗蛛：马蹄潮蛛Hygropoda hippocrepiforma Wang,1993和带形盗蛛Pisaura zonaformis Wang,1993的分类地位进行了修订。研究结果表明,马蹄溯蛛Hygropoda hippocrepiforma Wang,1993为长肢溯蛛Hygropoda higenaga(Kishida,1936)的新异名,移带形盗蛛Pisaura zonaformis Wang ,1993到东洋蛛属Polyboea,该属亦为我国新记录属。