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Exposure to nickel, an environmental respiratory toxicant, is associated with lung diseases including asthma, pulmonary fibrosis, bronchitis and cancers. Our previous studies have shown that a majority of the nickel-induced transcriptional changes are persistent and do not reverse even after the termination of exposure. This suggested transcriptional memory, wherein the cell 'remembers' past nickel exposure. Transcriptional memory, due to which the cells respond more robustly to a previously encountered stimulus has been identified in a number of organisms. Therefore, transcriptional memory has been described as an adaptive mechanism. However, transcriptional memory caused by environmental toxicant exposures has not been well investigated. Moreover, how the transcriptional memory caused by an environmental toxicant might influence the outcome of exposure to a second toxicant has not been explored. In this study, we investigated whether nickel-induced transcriptional memory influences the outcome of the cell's response to a second respiratory toxicant, nicotine. Nicotine, an addictive compound in tobacco, is associated with the development of chronic lung diseases including chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Our results show that nicotine exposure upregulated a subset of genes only in the cells previously exposed to nickel. Furthermore, our analyses indicate robust activation of interferon (IFN) signaling in these cells. IFN signaling is a driver of inflammation, which is associated with many chronic lung diseases. Therefore, our results suggest that nicotine exposure of lung cells that retain the transcriptional memory of previous nickel exposure could result in increased susceptibility to developing chronic inflammatory lung diseases. • This study investigates the consequences of nickel-induced transcriptional memory. • Nicotine upregulated a unique set of genes only in the cells previously exposed to nickel. • Nicotine activated IFN signaling in the cells that retain the memory of previous nickel exposure. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a known human lung carcinogen. In addition, Cd exposure is associated with several lung diseases including emphysema, chronic obstructive pulmonary disease (COPD), asthma and fibrosis. Although earlier studies have identified several processes dysregulated by Cd exposure, the underlying mechanisms remain unclear. Here, we examined the transcriptome of lung epithelial cells exposed to Cd to understand the molecular basis of Cd-induced diseases. Computational analysis of the transcriptome predicted a significant number of Cd-upregulated genes to be targets of miR-30 family miRNAs. Experimental validation showed downregulation of all the miR-30 family members in Cd exposed cells. We found SNAIL, an EMT master regulator, to be the most upregulated among the miR-30 targets. Furthermore, we found decrease in the levels of epithelial marker E - cadherin (CDH1) and increase in the levels of mesenchymal markers, ZEB1 and vimentin. This suggested induction of EMT in Cd exposed cells. Luciferase reporter assays showed that miR-30 repressed SNAIL by directly targeting its 3′ UTR. Over expression of miR-30e and transfection of miR-30e mimics reduced Cd-induced SNAIL upregulation. Our results suggest that miR-30 negatively regulates SNAIL in lung epithelial cells and that Cd-induced downregulation of miR-30 relieves this repression, resulting in SNAIL upregulation and EMT induction. EMT plays a major role in many diseases associated with Cd exposure including fibrosis, COPD, and cancer and metastasis. Therefore, our identification of miR-30 downregulation in Cd exposed cells and the consequent activation of SNAIL provides important mechanistic insights into lung diseases associated with Cd exposure. • A number of genes upregulated by Cd exposure are targets of miR-30 family miRNAs. • miR-30 family is downregulated in Cd exposed BEAS-2B and BEP2D cells. • Cd induced miR-30 repression caused upregulation of the EMT master regulator, SNAIL. • miR-30e overexpression and miR30e mimics prevented Cd-induced SNAIL upregulation. [ABSTRACT FROM AUTHOR]

Trehalose could protect the typical food microorganism Saccharomyces cerevisiae cell against environmental stresses; however, the other regulation effects of trehalose on yeast cells during the fermentation are still poorly understood. In this manuscript, different concentrations (i.e., 0, 2 and 5% g/v) of trehalose were respectively added into the medium to evaluate the effect of trehalose on growth, central metabolisms and division of S. cerevisiae CEN.PK113-7D strain that could uptake exogenous trehalose. Results indicated that addition of trehalose could inhibit yeast cell growth in the presence or absence of 8% v/v ethanol stress. Exogenous trehalose inhibited the glucose transporting efficiency and reduced intracellular glucose content. Simultaneously, increased intracellular trehalose content destroyed the steady state of trehalose cycle and caused the imbalance between the upper glycolysis part and the lower part, thereby leading to the dysfunction of glycolysis and further inhibiting the normal yeast cell growth. Moreover, energy metabolisms were impaired and the ATP production was reduced by addition of trehalose. Finally, exogenous trehalose-associated inhibition on yeast cell growth and metabolisms delayed cell cycle. These results also highlighted our knowledge about relationship between trehalose and growth, metabolisms and division of S. cerevisiae cells during fermentation. • Exogenous trehalose could inhibit S. cerevisiae CEN.PK113-7D cell growth. • Trehalose inhibited the glucose transporting efficiency of S. cerevisiae cells. • Trehalose caused imbalance between upper glycolysis part and lower part. • Exogenous trehalose impaired the energy metabolisms of S. cerevisiae cells. • Exogenous trehalose could delay yeast cell cycle. [ABSTRACT FROM AUTHOR]

Abstract A sensitive surface-enhanced Raman scattering (SERS) approach has been developed for detection of microRNA (miRNA) based on target-triggered dual signal amplification including strand displancement amplification (SDA) and hybridization chain reaction (HCR). With the assistant of polymerase and nicking endonuclease (NEase), target miRNA combines with the single stranded template DNA to generate a great amount of trigger DNA which can induce HCR. Coupled the dual cycle amplification of SDA and HCR with the dual enhancement of gold nanoparticles (AuNPs), a low detection limit of 0.5 fM for miRNA is obtained using the proposed strategy. With high sensitivity, universality, rapid analysis, and high selectivity, this method has a great potential for detecting biomolecules with trace amounts in bioanalysis and clinical biomedicine. Highlights • A novel method of dual cycle amplification and dual signal enhancement assisted SERS detection for miRNA is developed. • This method allows the transduction of miRNA detection into DNA-based signal amplification. • This assay has the advantages of wide dynamic range, high sensitivity and selectivity. [ABSTRACT FROM AUTHOR]

Detection of ultralow concentrations of nucleic acid sequences is a central challenge in the early diagnosis of genetic diseases. Herein, we developed a target-triggering cascade multiple cycle amplification for ultrasensitive DNA detection using quartz crystal microbalance (QCM) and surface plasmon resonance (SPR). It was based on the exonuclease Ⅲ (Exo Ⅲ)-assisted signal amplification and the hybridization chain reaction (HCR). The streptavidin-coated Au-NPs (Au-NPs-SA) were assembled on the HCR products as recognition element. Upon sensing of target DNA, the duplex DNA probe triggered the Exo Ⅲ cleavage process, accompanied by generating a new secondary target DNA and releasing target DNA. The released target DNA and the secondary target DNA were recycled. Simultaneously, numerous single strands were liberated and acted as the trigger of HCR to generate further signal amplification, resulting in the immobilization of abundant Au-NPs-SA on the gold substrate. The QCM sensor results were found to be comparable to that achieved using a SPR sensor platform. This method exhibited a high sensitivity toward target DNA with a detection limit of 0.70 fM. The high sensitivity and specificity make this method a great potential for detecting DNA with trace amounts in bioanalysis and clinical biomedicine. [ABSTRACT FROM AUTHOR]

Abstract: Methyl-CpG (mCpG) binding domain protein 4 (MBD4) is a member of mammalian DNA glycosylase superfamily. It contains an amino-proximal methyl-CpG binding domain (MBD) and a C-terminal mismatch-specific glycosylase domain, which is an important molecule believed to be involved in maintaining of genome stability. Herein, we determined the crystal structure of C-terminal glycosylase domain of human MBD4. And the structural alignments of other helix-hairpin-helix (HhH) DNA glycosylases show that the human MBD4 glycosylase domain has the similar active site and the catalytic mechanisms as others. But the different residues in the N-terminal of domain result in the change of charge distribution on the surface of the protein, which suggest the different roles that may relate some diseases. [Copyright &y& Elsevier]

Abstract: Enterocyte apoptosis in necrotizing enterocolitis is partly due to the elaboration of toxic intermediates of nitric oxide (NO), such as peroxynitrite (PN). Because p38 mitogen-activated protein kinase (MAPK) and serine–threonine kinase (AKT) are well-characterized pro- and anti-apoptotic mediators, respectively, we hypothesized that PN could induce enterocyte apoptosis via activation of p38 and deactivation of AKT. To test this hypothesis, the rat intestinal cell line, IEC-6, was treated with PN. PN caused phosphorylation of p38, its upstream activator, MKK3/6, and downstream effector, transcription factor ATF-2. PN-induced apoptosis was inhibited by the p38 inhibitor, SB202190, and by p38 siRNA. PN decreased AKT phosphorylation; this effect was abrogated by pre-treatment with SB202190 or p38 siRNA. PN exposure also increased the activity of the protein phosphatase 2A (PP2A). These data demonstrate that PN-mediated apoptosis depends on the p38 pathway and that p38 mediates deactivation of AKT survival pathways possibly by the involvement of PP2A. [Copyright &y& Elsevier]

Foods prepared by fermentation with Saccharomyces cerevisiae sometimes require co-cultivation with lactic acid bacteria (LAB) or other microorganisms. Co-cultured LAB could compete for nutrients, thereby affecting central metabolism of S. cerevisiae cells; as a result, the oxidative metabolism of yeast might also be influenced. Here, S. cerevisiae ATCC 204508 was co-cultivated with Lactobacillus plantarum ATCC 8014 to evaluate its regulation effects on the oxidative metabolism in yeast cells. Results indicated that co-cultured L. plantarum did not exacerbate membrane lipid peroxidation but reduced intracellular reactive oxygen species (ROS) content of yeast. L. plantarum initiated NADPH oxidase by activation of Ca2+ signaling and MAPK pathways, thereby promoting the ROS generation in S. cerevisiae cells. To cope with the increased ROS generation, both enzymatic and non-enzymatic defense systems were activated, accounting for the decreased intracellular ROS level in yeast cells that co-cultured with L. plantarum. At the same time, activated anti-oxidation system also conferred higher oxidative tolerance to yeast cells, which could be considered a desirable characteristic for fermentation using S. cerevisiae. The co-cultivation of L. plantarum also activated energy metabolism and promoted ATP production in yeast. These results will contribute to the understanding of the complex relationship between S. cerevisiae and LAB during fermentation. • Co-existed L. plantarum decreased intracellular ROS content of S. cerevisiae. • Co-existed L. plantarum activated ROS generation in S. cerevisiae cells. • Co-existed L. plantarum activated anti-oxidation system in S. cerevisiae cells. • Co-existed L. plantarum promoted oxidative tolerance of S. cerevisiae. • Co-existed L. plantarum activated energy metabolisms of S. cerevisiae cells. [ABSTRACT FROM AUTHOR]