Prognostic value of periostin in multiple solid cancers: A systematic review with meta-analysis

Previous studies have shown that the expression of periostin (POSTN) is significantly correlated with prognosis in multiple solid cancers. However, the function of POSTN in tumorigenesis and its relationship with clinical outcomes have not been systematically summarized and analyzed. Thus, a meta-analysis was performed to evaluate the prognostic pertinence of POSTN in solid cancer. We conducted a systematic search in the PubMed, EMBASE, Web of Science, and Cochrane library databases, and a total of 10 studies were used to assess the association of POSTN expression and patients’ overall survival (OS) and disease-free survival (DFS). The hazard ratio (HR) or odds ratio (OR) and their corresponding 95% confidence intervals (95% CIs) were further calculated to estimate the association between POSTN and relevant clinical parameters of solid cancer patients. The pooled results indicated that POSTN overexpression was associated with poor OS (HR = 2.35, 95% CI = 1.88–2.93, p < .00001) and DFS (HR = 2.70, 95% CI = 2.00–3.65, p < .00001) in a cohort of 993 patients with cancer. Subsequent analyses showed that the positive expression ratio of POSTN was evidently higher in cancer tissues than in normal tissues (OR = 7.44, 95% CI = 3.66–13.95, p < .00001). In addition, subgroup analysis showed that POSTN was related to microvascular invasion (OR = 5.09, 95% CI = 3.07–8.44, p < .00001), tumor differentiation (OR = 2.03, 95% CI = 1.41–2.91, p = .0001), and lymph node metastasis (OR = 3.05, 95% CI = 2.01–4.64, p < .00001). These data showed that POSTN could be a credible prognostic biomarker and a potential therapeutic target in human solid cancer.     

PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling

Plastin-3 plays a key role in cancer cell proliferation and invasion, but its prognostic value in pancreatic cancer (PACA) remains poorly defined. In this study, we show that PLS3 messenger RNA is overexpressed in PACA tissue compared with normal tissue. We accumulated 207 cases of PACA specimens to perform immunohistochemical analysis and demonstrated that PLS3 levels correlate with T-classification (p < .001) and pathology (p < .001). Furthermore, overall survival rates (p < .001) in tumors with high PLS3 expression were poor, as assessed through Kaplan–Meier survival analysis. PLS3 was found to be an independent prognostic factor for PACA through multivariate Cox regression analysis. Moreover, we found that PLS3 enhances the proliferation and invasion of tumor cells as assessed through Cell Counting Kit-8, wounding healing assays, and Transwell assays. The upregulation of PLS3 also led to enhanced phosphatidylinositol-3 kinase/protein kinase B signaling in PACA cells. These data suggest that PLS3 is a biomarker to estimate PACA progression and represents a molecular target for PACA therapy.     

The Helicobacter pylori Protein CagM is Located in the Transmembrane Channel That is Required for CagA Translocation

Helicobacter pylori (H. pylori) is a human gastric pathogen that colonizes the stomach in more than 50 % of the world’s human population. Infection with this bacterium can induce several gastric diseases ranging from gastritis to peptic ulcer and gastric cancer. Virulent H. pylori isolates harboring the cag pathogenicity island (cag PAI), which encodes a Type IV Secretion System (T4SS), form a pilus for the injection of its major virulence protein CagA into gastric cells. Several cag PAI genes have been identified as homologues of T4SS genes from Agrobacterium tumefaciens, while the other members in cag PAI still have no known function. We studied one of such proteins with unknown function, CagM, which was predicted to have a putative N-terminal signal sequence and at least three transmembrane helices. To determine the subcellular localization of CagM, we performed a cell fractionation procedure and produced rabbit anti-CagM polyclonal antibodies for immunoblotting assays. Furthermore, we generated an isogenic ΔcagM mutant to investigate the ability of CagA translocation compared with the wild-type NCTC 11637 strain using GES-1 and MKN-45 cell infection experiments. Our results indicated that CagM was mainly located in the bacterial membrane, partially located in the periplasm, and essential for CagA translocation both in GES-1 and MKN-45 cells, which suggested that CagM was one of the core members of Cag T4SS and localized in the transmembrane channel.     

The Expression Pattern of Classical MHC Class I Molecules in the Development of Mouse Central Nervous System

Classical major histocompatibility complex (MHC) class I, first identified in the immune system, is also expressed in the developing and adult central nervous system (CNS). Although the MHC class I molecules have been found to be expressed in the CNS of different species, a necessary step to elucidate the temporal and spatial expression patterns of MHC class I molecules in the brain development has never been taken. Frozen sections were made from the brains of embryonic and postnatal C57BL/6 J mice, and the expression of H-2D^b mRNA was examined by in situ hybridization. Immunofluorescence was also performed to define the cell types that express H2-D^b in P15 mice. At E10.5, the earliest stage we examined, H2-D^b was expressed in neuroepithelium of the brain vesicles. From E12.5 to P0, H2-D^b expression was mainly located at cerebral cortex, neuroepithelium of the lateral ventricle, neuroepithelium of aquaeductus and developing cerebellum. From P4 to adult, H2-D^b mRNA was detected at olfactory bulb, hippocampus, cerebellum and some nerve nuclei. The major cell types expressing H-2D^b in P15 hippocampus, cerebral cortex and olfactory bulb were neuron. H2-K^b signal paralleled that of H2-D^b and the expression levels of the two molecules were comparable throughout the brain. The investigation of the expression pattern of H-2D^b at both embryonic and postnatal stages is important for further understanding the physiological and pathological roles of H2-D^b in the developing CNS.     

DISC1-related signaling pathways in adult neurogenesis of the hippocampus

Disrupted-in-schizophrenia 1 (DISC1) is a multifunctional scaffold protein which plays an important role in neurogenesis and neural development in the adult brain, especially in the dentate gyrus (DG) of the hippocampus. Accumulated research has unveiled the role of DISC1 in several aspects of neural development and neurogenesis, such as neuronal maturation, proliferation, migration, positioning, differentiation, dendritic growth, axonal outgrowth, and synaptic plasticity. Studies on the function of this protein have explored multiple facets, including variants and missense mutants in genetics, proteins interactivity and signaling pathways in molecular biology, and pathogenesis and treatment targets of major mental illness, and more. In this review, we present several signaling pathways discussed in recent research, such as the AKT signaling pathway, GABA signaling pathway, GSK3β signaling pathway, Wnt signaling pathway, and NMDA-R signaling pathway. DISC1 interacts, directly or indirectly, with these signaling pathways and they co-regulate the process of adult neurogenesis in the hippocampus.     

Transactivation of Atg4b by C/EBPβ Promotes Autophagy To Facilitate Adipogenesis

Autophagy is a highly conserved self-digestion pathway involved in various physiological and pathophysiological processes. Recent studies have implicated a pivotal role of autophagy in adipocyte differentiation, but the molecular mechanism for its role and how it is regulated during this process are not clear. Here, we show that CCAAT /enhancer-binding protein β (C/EBPβ), an important adipogenic factor, is required for the activation of autophagy during 3T3-L1 adipocyte differentiation. An autophagy-related gene, Atg4b, is identified as a de novo target gene of C/EBPβ and is shown to play an important role in 3T3-L1 adipocyte differentiation. Furthermore, autophagy is required for the degradation of Klf2 and Klf3, two negative regulators of adipocyte differentiation, which is mediated by the adaptor protein p62/SQSTM1. Importantly, the regulation of autophagy by C/EBPβ and the role of autophagy in Klf2/3 degradation and in adipogenesis are further confirmed in mouse models. Our data describe a novel function of C/EBPβ in regulating autophagy and reveal the mechanism of autophagy during adipocyte differentiation. These new insights into the molecular mechanism of adipose tissue development provide a functional pathway with therapeutic potential against obesity and its related metabolic disorders.     

Association of two variants in the interleukin-6 receptor gene and premature coronary heart disease in a Chinese Han population

Two novel single nucleotide polymorphisms (SNPs; rs7529229 and rs2228145) in the interleukin-6 receptor (IL6R) gene have recently been associated with coronary heart disease (CHD) in a European population. We sought to replicate this finding and to investigate associations of these two SNPs with the severity and clinical phenotypes of premature CHD in a Chinese Han population. A total of 418 patients were studied, including 187 cases with coronary stenosis ≥50 % or acute myocardial infarction (males < 55 years and females < 65 years) and 231 controls without documented CHD. A ligase detection reaction was performed to detect rs7529229 and rs2228145. There were no differences between the controls and premature CHD groups in the frequencies for the three genotypes and alleles of rs7529229 and rs2228145 (all P > 0.05), nor did they differ between the two groups when grouped by gender (all P > 0.05). There were also no associations between these two SNPs and the severity of coronary lesions or clinical phenotypes of premature CHD (all P > 0.05). Our results do not support an association between rs7529229 or rs2228145 with premature CHD in the Chinese Han population. Further studies are warranted to elucidate the role of these two SNPs in the development of atherosclerosis and CHD.     

Genome-wide screen for aberrantly expressed miRNAs reveals miRNA profile signature in breast cancer

Dysregulation in the expression of miRNAs contributes to the occurrence and development of many human cancers. We herein attempted to obtain the potential association between miRNA expression profile and breast cancer by applying high-throughput sequencing technology. Small RNAs from seven paired tumor and adjacent normal tissue samples were sequenced. To determine the miRNA expression profiles in tissues and sera, another five equally pooled serum samples from 20 patients and 30 normal women were sequenced. Despite a similar number in abundantly expressed miRNAs across samples, we detected varying miRNA expression profiles. Some miRNAs showed inconsistent or opposite dysregulation trends across different tumor tissues, including some abundantly expressed miRNA gene clusters and gene families. Wilcoxon sign-rank test for paired samples analysis revealed that abnormal miRNAs showed a higher level of variation across the seven tumor samples. We also completely surveyed abnormal miRNAs expressed in tumor and serum tissues in the mixed datasets based on the relative expression levels. Most of these miRNAs were significantly down-regulated in tumor samples, but nine abnormal miRNAs (miR-18a, 19a, 20a, 30a, 103b, 126, 126*, 192, 1287) were consistently expressed in tumor tissues and serum samples. Based on experimentally validated target mRNAs, functional enrichment analysis indicated that these abnormal miRNAs and miRNA groups (miRNA gene clusters and gene families) have important roles in multiple biological processes. Dynamic miRNA expression profiles, various abnormal miRNA profiles and complexity of the miRNA regulatory network reveal that the miRNA expression profile is a potential biomarker for classifying or detecting human disease.     

HRAS: a webserver for early warning of human health risk brought by aflatoxin

Most people are aware that outdoor air pollution can damage their health, but many do not know that indoor air pollution can also exhibit significant negative health effects. Fungi parasitizing in air conditioning and ventilation systems can be one of indoor air pollution sources. Aflatoxin produced by Aspergillus flavus (A. flavus) became a central focus of indoor air pollution, especially in farmer markets. Therefore we developed an early warning system, Health Risk Assessment System, to estimate the growth rate of A. flavus, predict the amount of aflatoxin and provide early warning information. Firstly, the growth of A. flavus and the production of aflatoxin under different conditions were widely obtained through a comprehensive literature review. Secondly, three mathematical models were established to predict the A. flavus colony growth rate, lag phase duration and aflatoxin content, as functions of temperature and water activity based on present studies. Finally, all the results were evaluated by the user-supplied data using PHP programming language. We utilized the web page to show the results and display warning information. The JpGraph library was used to create a dynamic line chart, refreshing the warning information dynamically in real-time. The HARS provides accurate information for early warning purposes to let us take timely steps to protect ourselves.