Microarray analysis reveals the changes of circular RNA expression and molecular mechanism in acute lung injury mouse model

Acute lung injury (ALI) is a severe disease with sudden onset, rapid progression, poor treatment response, and high mortality. An increasing number of studies had found that circular RNAs (circRNAs) has significant functions in various diseases, while the role of circRNAs in ALI is not yet clear. The purpose of this study was to find circRNAs related to ALI and their mechanism of action. Expression profiles of lung circRNAs and messenger RNAs (mRNAs) were analyzed by microarray in the ALI mice models and healthy controlled mice. Differentially expressed RNAs were identified, function and pathways were analyzed by bioinformatics analysis. Moreover, the results of the microarray were verified by real-time PCR. We identified 2262 differentially expressed mRNAs and 581 circRNAs between ALI mice and control. Validation of candidate circRNAs by real-time PCR indicates that the majority of circRNAs identified by microarray are reliable and worthy of further study. ALI induced circRNAs primarily function in the metabolic regulatory process. Moreover, differentially expressed circRNAs were mainly involved in signaling pathways of mitogen-activated protein kinases, focal adhesion, FoxO, neurotrophin, and Wnt. In addition, a competitive endogenous RNA network was constructed to further interpret the molecular mechanism of ALI. This study observed significantly changed circRNAs profiles in LPS-induced mouse model and revealed a potential role of circRNAs in ALI.     

Down-regulated expression of LINC00518 prevents epithelial cell growth and metastasis in breast cancer through the inhibition of CDX2 methylation and the Wnt signaling pathway

Breast cancer (BC)-related mortality is associated with the potential metastatic properties of the primary breast tumors. The following study was conducted with the main focus on the effect of LINC00518 on the growth and metastasis of BC epithelial cells via the Wnt signaling pathway through regulation of the methylation of CDX2 gene. Initially, differentially expressed long intergenic non-protein coding RNAs (lincRNAs) related to BC were screened out in the Cancer Genome Atlas (TCGA) database, after which we detected the LINC00518 expression and localization in BC tissues and cells. Then the CDX2 positive expression and methylation level were identified. The targeting relationship of LINC00518 and CDX2, and binding methyltransferase in the promoter region were examined. BC epithelial cell proliferation, colony formation ability, invasion, migration and apoptosis were further evaluated. The lincRNA expression data related to BC downloaded from the TCGA database revealed that there was a high expression of LINC00518 in BC, and a negative correlation between LINC00518 and CDX2. In addition, LINC00518 promotes CDX2 methylation by recruiting DNA methyltransferase through activating the Wnt signaling pathway. The down-regulation of LINC00518 inhibited proliferation, invasion, migration, and EMT of BC epithelial cells while enhancing apoptosis. The inhibitory effects of LINC00518 down-regulation was reversed by CDX2 down-regulation. In conclusion, our findings revealed that down-regulation of LINC00518 might have the ability to suppress BC progression by up-regulating CDX2 expression through the reduction of methylation and blockade of the Wnt signaling pathway, resulting in the inhibition of proliferation and promotion of apoptosis of BC epithelial cells.     

Paleoepidemiology,healing, and possible treatment of trauma in the medieval cemetery population of St. Helen-on-the-Walls,York, England

Traumatic lesions are commonly found in the archeological record and have potential to provide insight into the lives of past populations. This paper examines patterns of long bone fractures in the British medieval population of St. Helen-on-the-Walls from York (approximately 1100–1550) in an effort to determine patterns of healing and evidence for treatment. Long bones were macroscopically and radiologically examined. Clinical data were used to assess whether a fracture had successfully or unsuccessfully healed. The results indicate that fractures of the radius and ulna were most common. Males displayed more fractures than women. Most fractures were healed, well aligned, and without substantial deformity. Lack of evidence for deformity in bones likely to be severely affected by fracture implied that immobilization and possibly reduction was practiced on even the poorest residents of the medieval city. © 1996 Wiley-Liss, Inc.     

Downregulation of lncRNA APCDD1L-AS1 due to DNA hypermethylation and loss of VHL protein expression promotes the progression of clear cell renal cell carcinoma

Background: The current studies only indicated that long non-coding RNA (lncRNA) APCDD1L-AS1, as a novel lncRNA, may play a role in oral squamous cell carcinoma and lung cancer. However, its potential role in clear cell renal cell carcinoma (ccRCC) and its possible mechanism of action remain vague.Methods: TCGA-KIRC and GEO data and qRT-PCR and pyrosequencing results of clinical specimens were used to identify the expression level and DNA methylation status of APCDD1L-AS1. The effects of APCDD1L-AS1 overexpression on ccRCC growth and metastasis were determined by function experiments. Western blot and Tandem mass tags (TMT) were utilized to explore the relationship between APCDD1L-AS1 and VHL expression and its downstream underlying mechanisms.Results: The expression of APCDD1L-AS1 was downregulated in ccRCC. Decreased APCDD1L-AS1 expression was related to higher tumor stage and histological grade and shorter RFS (Relapse-free survival). Besides, APCDD1L-AS1 overexpression restrained the growth and metastasis of ccRCC cells in vitro and in vivo. Moreover, reduced APCDD1L-AS1 expression could be caused by DNA hypermethylation and loss of von Hippel Lindau (VHL) protein expression. Furthermore, the dysregulation of histones expression caused by APCDD1L-AS1 overexpression may be one of the important mechanisms to suppress the progression of ccRCC.Conclusion: APCDD1L-AS1 was able to inhibit the progression of ccRCC, and its decreased expression could be caused by DNA hypermethylation and loss of VHL protein expression. Therefore, APCDD1L-AS1 may serve as a new therapeutic target in the treatment of ccRCC.     

Innate,translation‐dependent silencing of an invasive transposon in Arabidopsis

Co‐evolution between hosts’ and parasites’ genomes shapes diverse pathways of acquired immunity based on silencing small (s)RNAs. In plants, sRNAs cause heterochromatinization, sequence degeneration, and, ultimately, loss of autonomy of most transposable elements (TEs). Recognition of newly invasive plant TEs, by contrast, involves an innate antiviral‐like silencing response. To investigate this response’s activation, we studied the single‐copy element EVADÉ (EVD), one of few representatives of the large Ty1/Copia family able to proliferate in Arabidopsis when epigenetically reactivated. In Ty1/Copia elements, a short subgenomic mRNA (shGAG) provides the necessary excess of structural GAG protein over the catalytic components encoded by the full‐length genomic flGAG‐POL. We show here that the predominant cytosolic distribution of shGAG strongly favors its translation over mostly nuclear flGAG‐POL. During this process, an unusually intense ribosomal stalling event coincides with mRNA breakage yielding unconventional 5’OH RNA fragments that evade RNA quality control. The starting point of sRNA production by RNA‐DEPENDENT‐RNA‐POLYMERASE‐6 (RDR6), exclusively on shGAG, occurs precisely at this breakage point. This hitherto‐unrecognized “translation‐dependent silencing” (TdS) is independent of codon usage or GC content and is not observed on TE remnants populating the Arabidopsis genome, consistent with their poor association, if any, with polysomes. We propose that TdS forms a primal defense against EVD de novo invasions that underlies its associated sRNA pattern.     

辽西褐土施肥及养分循环再利用中长期试验Ⅳ.土壤肥力变化

经12年田间试验,各施肥处理耕层土壤的肥力变化表明,在保持农业系统养分循环再利用基础上,施用适量化肥以平衡土壤养分收支,不仅可实现作物高产,减少过剩养分进入环境,并可改善土壤肥力,表现为明显提高了耕层的有机C,N浓度,不过,在本例中欲保持较高的土壤有效P水平,恐需在平均土壤P收支基础上适当增加P肥施用量。     

人骨髓基质细胞的长期培养及其对病毒的敏感性

为了长期培养骨髓基质细胞和研究其对病毒的敏感性,我们采用静置贴壁培养法,体外长期培养了胎儿、儿童和成人骨髓基质细胞,并将传至５代以上的肌样骨髓基质细胞采用微量细胞病变（ＣＰＥ）法,开展了对５种病毒的敏感性试验。结果表明,人骨髓基质肌样细胞对滤泡性口腔炎病毒,脊髓灰质炎病毒、Ⅰ型和Ⅱ型单纯疱疹病毒均敏感,能产生明显的ＣＰＥ,其效价（ＴＣＩＤ５０）可达１０＾－３～１０＾－４,其中胎儿骨髓基质肌样细胞对     

Identification of functional lncRNAs in gastric cancer by integrative analysis of GEO and TCGA data

Gastric cancer (GC) is a prevalent malignant cancer of digestive system, identification of novel diagnostic and prognostic biomarkers for GC is urgently demanded. The aim of this study was to determine potential long noncoding RNAs (lncRNAs) associated with the pathogenesis and prognosis of GC. Raw noncoding RNA microarray data (GSE53137, GSE70880, and GSE99417) was downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes between GC and adjacent normal gastric tissue samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Differentially expressed genes were further confirmed by The Cancer Genome Atlas (TCGA) database. Competing endogenous RNA (ceRNA) network, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway, survival analysis were extensively applied to identify hub lncRNAs and discover potential biomarkers related to diagnosis and prognosis of GC. In total of 246 integrated differential genes including 15 lncRNAs and 241 messenger RNAs (mRNAs) were obtained after intersections of differential genes between GEO and TCGA database. ceRNA network comprised of three lncRNAs (UCA1, HOTTIP, and HMGA1P4), 26 microRNAs (miRNAs) and 72 mRNAs. Functional analysis revealed that three lncRNAs were mainly dominated in cell cycle and cellular senescence. Survival analysis showed that HMGA1P4 was statistically related to the overall survival rate. For the first time, we identified that HMGA1P4, a target of miR-301b/miR-508, is involved in cell cycle and senescence process by regulating CCNA2 in GC. Finally, the expression levels of three lncRNAs were validated to be upregulated in GC tissues. Thus, three lncRNAs including UCA1, HOTTIP, and HMGA1P4 may contribute to GC development and their potential functions might be associated with the prognosis of GC.