Exploring the molecular mechanism of Chlorella vulgaris in response to androstenedione exposure based on genes continuously up-regulated in transcription analysis.

Androstenedione (ADSD) is one of the widely detected androgens in diverse aquatic environments. However, there were few reports on the molecular mechanism of Chlorella vulgaris exposure to ADSD. In our previous research, we have investigated the genes associated with chlorophyll metabolism in Chlorella vulgaris response to ADSD. In this study, we focus on continuously up-regulated genes to explore the mechanism underlying Chlorella vulgaris resistance to ADSD toxicity. Chlorella vulgaris was exposed to ADSD with five concentration gradients. The continuously up-regulated genes were enriched by Series Test of Cluster (STC) analysis and verified by qRT-PCR. Microalgae Super Oxidase Dimutase (SOD) and Microalgae Malonic dialdehyde (MDA), two indicators of oxidative stress, were determined by ELISA after exposure to ADSD. The results showed that ADSD can stimulate the production of extracellular polymeric substances (EPS) and lead to enlargement in the cell body of Chlorella vulgaris. In addition, steroid biosynthesis and oxidoreductase activity processes were consistently up-regulated upon exposure to ADSD. In conclusion, our study highlighted the crucial role of phenotypic modification, hormone synthesis, and redox mechanisms in protecting Chlorella vulgaris cells from the harmful effects of ADSD contamination.

Identification of New Key Genes and Their Association with Breast Cancer Occurrence and Poor Survival Using In Silico and In Vitro Methods.

Breast cancer is one of the most prevalent types of cancer diagnosed globally and continues to have a significant impact on the global number of cancer deaths. Despite all efforts of epidemiological and experimental research, therapeutic concepts in cancer are still unsatisfactory. Gene expression datasets are widely used to discover the new biomarkers and molecular therapeutic targets in diseases. In the present study, we analyzed four datasets using R packages with accession number GSE29044, GSE42568, GSE89116, and GSE109169 retrieved from NCBI-GEO and differential expressed genes (DEGs) were identified. Protein-protein interaction (PPI) network was constructed to screen the key genes. Subsequently, the GO function and KEGG pathways were analyzed to determine the biological function of key genes. Expression profile of key genes was validated in MCF-7 and MDA-MB-231 human breast cancer cell lines using qRT-PCR. Overall expression level and stage wise expression pattern of key genes was determined by GEPIA. The bc-GenExMiner was used to compare expression level of genes among groups of patients with respect to age factor. OncoLnc was used to analyze the effect of expression levels of LAMA2, TIMP4, and TMTC1 on the survival of breast cancer patients. We identified nine key genes, of which COL11A1, MMP11, and COL10A1 were found up-regulated and PCOLCE2, LAMA2, TMTC1, ADAMTS5, TIMP4, and RSPO3 were found down-regulated. Similar expression pattern of seven among nine genes (except ADAMTS5 and RSPO3) was observed in MCF-7 and MDA-MB-231 cells. Further, we found that LAMA2, TMTC1, and TIMP4 were significantly expressed among different age groups of patients. LAMA2 and TIMP4 were found significantly associated and TMTC1 was found less correlated with breast cancer occurrence. We found that the expression level of LAMA2, TIMP4, and TMTC1 was abnormal in all TCGA tumors and significantly associated with poor survival.

Bioinformatics Analysis of Up-regulated Differential Genes in Rats post Spinal Cord Injury / 中国康复理论与实践

Objective:To investigate the differential expression and gene functions of up-regulated genes in rats with spinal cord injury. Methods:Female Sprague-Dawley rats' model of spinal cord injury was established with the modified Allen's method. Gene chip technology was used to detect the variation of differentially expressed genes in the spinal cord after spinal cord injury in rats. The differences in genes, functional localization and pathways were analyzed with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway database. Results:The results of total RNA quality in spinal cord segment were qualified. Gene chip results showed that there were 1874 differentially up-regulated genes and 2348 differentially down-regulated genes. Bioinformatics was used to analyze differentially up-regulated genes in terms of biological processes, cellular components, and molecular functions. The differentially up-regulated genes were involving apoptosis, immune response, inflammation, etc., pathway analysis mainly showed the differentially up-regulated genes involved phosphoinositide 3-kinase protein kinase B signaling pathway and Toll-like receptor signaling pathways. Conclusion:Differentially up-regulated genes may be involved in secondary reactions following spinal cord injury, such as inflammation, immune response and hypoxia, and then further affect motor function and sensory function.

African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.

BACKGROUND: Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. METHODS: To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. RESULTS: We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. CONCLUSION: Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.

Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens.

Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here.

Medicago truncatula genotypes Jemalong A17 and R108 show contrasting variations under drought stress.

Drought is one of the most significant abiotic stresses that restrict crop productivity. Medicago truncatula is a model legume species with a wide genetic diversity. We compared the differential physiological and molecular changes of two genotypes of M. truncatula (Jemalong A17 and R108) in response to progressive drought stress and rewatering. The MtNCED and MtZEP activation and higher abscisic acid (ABA) content was observed in Jemalong A17 plants under normal conditions. Additionally, a greater increase in ABA content and expression of MtNCED and MtZEP in Jemalong A17 plants than that of R108 plants were observed under drought conditions. A more ABA-sensitive stomatal closure and a slower water loss was found in excised leaves of Jemalong A17 plants. Meanwhile, Jemalong A17 plants alleviated leaf wilting and maintained higher relative water content under drought conditions. Exposed to drought stress, Jemalong A17 plants exhibited milder oxidative damage which has less H2O2 and MDA accumulation, lower electrolyte leakage and higher chlorophyll content and PSII activity. Furthermore, Jemalong A17 plants enhanced expression of stress-upregulated genes under drought conditions. These results suggest that genotypes Jemalong A17 and R108 differed in their response and adaptation to drought stress. Given the relationship between ABA and these physiological responses, the MtNCED and MtZEP activation under normal conditions may play an important role in regulation of greater tolerance of Jemalong A17 plants to drought stress. The activation of MtNCED and MtZEP may lead to the increase of ABA content which may activate expression of drought-stress-regulated genes and cause a series of physiological resistant responses.