Abstract:Circular RNAs (circRNAs) represent a class of non-coding RNA widely spreading in eukaryotic cells, with the feathers of structural stability, high abundance, cell or tissue-specific expression and so on. They involve in the regulation gene expression by multiple acting mechanisms. For example, several circRNAs contain microRNAs (miRNAs) competition sites, acting as competing endogenous RNAs (ceRNAs) to sequester microRNAs and terminate their suppression of targets genes. Ever since 2013, circRNAs analysis has been a popular research in RNA fields. Recent studies show, circRNAs’ expression and action are related to the occurrence or progression of various diseases, development of biologic tissue and cell aging. Their different expression probably make them to be ideal biomarkers in disease diagnosis or identification tissue development. And the clarity of their mechanisms in diseases also make them to be with the potential of effective therapeutic targets. The construction of circRNA database, the development of prediction tools and the deeply studies of their mechanisms will give a more widely application foreground for circRNAs.

Abstract:The signal transduction and transcriptional activation factor 3 (STAT3) plays important roles in many physiological and pathological processes. Although STAT3 is not a classic member of master transcription factors of epithelial-mesenchymal transition (EMT), STAT3 has recently also been documented to be a mediator of tumor cell phenotypic plasticity, in turn affecting formation and phonotypic characteristic of circulating tumor cells, which are associated with invasion and metastases of tumor cells. Activation of STAT3 can translocate into the nucleus and bind to specific promoter sequences of various EMT master transcription factors such as Twist, Snail, and Slug, resulting in the initiation and resolution of EMT programs in malignant cells, which promotes invasion and metastases of developing tumors. On the other hand, inactivated STAT3 may also function as a molecular adaptor to inhibit EMT programs. Therefore, understanding of the interaction between STAT3 and EMT and its effects on circulating tumor cells may provide new approaches for treatment of metastatic carcinomas.

Abstract:Oncogene induced cell senescence is an important tumor suppressor mechanism in vivo and in vitro. Ras is one of the most frequently mutant oncogene in human cancers. However, Ras induced cell transformation and malignization happened sometimes even under the supervision of OIS, which implicated Ras may obtained some pathways to bypass OIS. This article took Ras signal pathway as the main clue, to summarize the key molecules involved in OIS progression induced by Ras and some potential OIS overcome mechanism of Ras.

Abstract:With the advance of mass spectrometry and experimental techniques, a huge amount of mass spectrometry (MS) data has been accumulated rapidly in the past few years. Usually, different database search engines are used to analyze the MS data for peptide and protein identification. Meanwhile, selection of all those assignments that are actually correct is one of the most daunting tasks in mass spectrometry based proteomics investigations. Target-decoy searching strategy has become one of the most popular strategies to control the fasle identification in MS/MS data analysis. In this paper, we first introduce the workflow of target-decoy database searching strategy. Then we summarize the quality control tools based on the target-decoy searching strategy. Besides, we point out the deficiency of target-decoy searching strategy and put forward mending measures. Finally, we carry on summary and outlook to target-decoy searching strategy.

Abstract:Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Many microRNAs (miRNAs) have been reported to be abnormally expressed in CRC. Recent studies have identified miR-92b as a potential oncogene in several types of cancer. However, the role of miR-92b in CRC has not been clarified. This study aimed to elucidate the role of miR-92b in CRC progression. Relative quantitative PCR revealed that miR-92b expression was significantly increased in human CRC tissues compared to the adjacent tissues. Overexpression of miR-92b in the colorectal cancer cell line SW620 substantially increased cell viability in vitro and xenograft tumor growth in vivo. Also, miR-92b was identified as a secreted miRNA, which can be detected in both cultured medium and the peripheral blood of xenograft mice. Furthermore, we demonstrated that c-MYC, which was also elevated in CRC tissues, promoted the transcription of miR-92b by regulating its promoter activity. Luciferase assay and Western blot analysis revealed that FBXW7 was a novel target of miR-92b and can be negatively regulated by c-MYC. As FBXW7 is a major E3 ligase of c-MYC, our data suggested a potential positive regulatory feedback loop among c-MYC, miR-92b and FBXW7 in CRC. Collectively, we partly provided evidence on how miR-92b is regulated and the potential implications of miR-92b in CRC diagnosis.

Abstract:Oxaliplatin is a third-generation platinum derivative which is especially efficient for gastric and colorectal cancer treatment. Most studies revealed that the target of oxaliplatin is DNA molecule. However, the key structures formed by oxaliplatin and DNA still controversial so far. In this study, the interactions between oxaliplatin and DNA in vitro have been studied by UV spectra and atomic force microscopy (AFM) so as to reveal the structural basis of its anticancer activity. The structural characteristic after the incubation oxaliplatin at different concentrations with DNA for different time was investigated on freshly cleaved highly ordered pyrolytic graphite (HOPG) surface by atomic force microscopy (AFM). Based on the observed results, the interaction mechanism between oxaliplatin and DNA was proposed. High resolution AFM observation indicated that oxaliplatin can induce structural changes of pUC19 DNA from the extended chains to the intertangled structures with many nodes, and finally to a compact particle after 24 h incubation. The present results revealed that electrostatic and coordination interactions are important to condense plasmid DNA to a compact particle which may significantly influence the activity and cytotoxicity of oxaliplatin.

Abstract:Glycosylation is a major modification process in post-translational modification of protein. Accurate prediction of O-linked glycosylation sites is a big challenging faced by machine-learning, for the fixed-model of O-linked glycosylation is not yet known. In this paper, on the basis of the largest-ever Steentoft database up to now, a new feature——chi-square score difference table method based on position (χ²-pos) was first proposed, which combined with pseudo position-specific scoring matrix (PsePSSM) and undirected composition of k-spaced amino acid pairs (Undirected-CKSAAP) were used to present protein sequences. Then 5 support vector machines models were constructed with the same proportion of positive and negative samples. At last, by weighted voting, our results showed that the prediction accuracy, Matthew’s correlation coefficient and area under ROC curve reached 89.62%, 0.79 and 0.96 respectively. They were superior to the literature report. It also demonstrated that the combination of three different features χ²-pos, PsePSSM and Undirected-CKSAAP has extensive application prospect in protein sites prediction such as glycosylation and phosphorylation.

Abstract:To examine the effect of bamboo leaf flavonoids on isoflurane-induced neuronal apoptosis and cognitive impairment in aged rats. The primary hippocampal neurons were isolated and cultured. After hippocampal neurons were treated with 2% isoflurane for 6 h, and treated with 50, 80 and 100 mg/L of bamboo leaf flavonoids, the cell proliferation was measured by MTT method and cell apoptosis was measured by flow cytometry. The rats were inhaled with 1.4% isoflurane for 2 h, and injected intraperitoneally with 25, 50 and 100 mg/kg of bamboo leaf flavonoids for 5 consecutive days. The cognitive functions were examined by Morris water maze. The hippocampus were isolated for the determinations of Aβ_1-42, TNF-α and INF-γ by ELISA. Results showed that bamboo leaf flavonoids significantly increased the proliferation of hippocampal neurons and suppressed hippocampal neurons apoptosis compared with isoflurane treatment only. The result of Morris water maze showed that bamboo leaf flavonoids significantly decreased average escape latent period and increased the frequency of crossing platform. The results of ELISA showed that bamboo leaf flavonoids suppressed the expression of Aβ_1-42, TNF-α and INF-γ in hippocampus. Our findings suggested that bamboo leaf flavonoids enhanced immunity of aged rats and suppressed the expression of Aβ_1-42, leading to the inhibition of isoflurane-induced neuronal apoptosis and cognitive impairment.

Abstract:Current research has determined that many cloned animals have heterogeneous DNA methylation profiles. However, few studies have compared the methylation profiles of both naturally produced lambs and cloned lambs created using somatic cell nuclear transfer. The paucity of research in this area is because of insufficient resources to study limited cloned offspring, the ovine genome, and ovine genomic imprinting. In this study, to show the degree of reprogramming in cloned lambs, we cloned the putative differentially methylated regions (DMRs) of Peg3 from sheep and analyzed the DNA methylation patterns in CpG islands and DMRs of the putative imprinted genes Peg3, Cdkn1c and Gtl2 in cloned lambs. We have provided evidence that Peg3 was highly methylated. The degree of methylation was 95.45% in the kidney and 88.18% in the lung of a natural sheep and 98.18% in the kidney and 87.27% in the lung for one cloned sheep. The bisulphite sequencing results for Cdkn1c show complete non-methylation (0%, 0.53%, 0.53%, 0.53%) in all samples. In addition, Gtl2 was hypomethylated in all lambs, from a linear correlation analysis, there were some differences in the quantitative values from both groups (correlation r² = 0.77). These data show that the DNA methylation status of the three imprinted genes was similar in cloned and natural lambs.

Abstract:In this paper, a human ventricular acidotic model with pathophysiological consequences of acidosis, such as reduced pH and highly activated calcium/calmodulin dependent protein kinaseⅡ(CaMKⅡ), was developed to analyze the functional influence of acidosis on cardiac electrical activity and ventricular arrhythmia. Dynamic changes of cellular and tissue electrical activity were simulated and the acidosis-induced changes of electrocardiogram waveform were quantified. Results demonstrated that acidosis led to shortened action potential duration and decreased transmural dispersion of repolarization, resulting in reduced QT interval and shortened amplitude and width of T wave. In addition, acidosis also resulted in high resting membrane potential and reduced maximum upstroke velocity, leading to the generation of slow conduction and conduction block. Most importantly, at the early stage of the post acidosis, sarcoplasmic reticulum calcium load increased calcium leak, leading to delayed afterdepolarizations in the cellular membrane potential and premature ventricular contractions in the cardiac tissue model. Slow conduction, conduction block and delayed afterdepolarizations collectively promote and facilitate the formation and maintenance of ventricular re-entry, which may convert into ventricular tachycardia. Therefore, triggered activities induced during post acidosis period play an important role in the genesis of post acidosis arrhythmias.