Project description:<p>Neonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.</p><p><br></p><p><strong>Untargeted fecal metabolomics</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4932' rel='noopener noreferrer' target='_blank'><strong>MTBLS4932</strong></a>.</p><p><strong>Targeted SCFA brain metabolomics</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4933' rel='noopener noreferrer' target='_blank'><strong>MTBLS4933</strong></a>.</p>
Project description:Transcriptome analysis of murine foetal NSCs (E14) after short-term (48 hours) and long-term (13 days) hypoxic (3% oxygen) culture compared to normoxic culture (21% oxygen) We focused on whole-transcriptome analyses using gene chip microarrays to compare expression profiles of NSCs cultured at hypoxic conditions to those of normoxic cells. Therefore, we used NSCs derived from the mesencephalon and the cortex and cultured them for short- and long-term at hypoxia/normoxia.
Project description:<p>Neonatal hypoxic-ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic-ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels was observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathological of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.</p><p><br></p><p><strong>Targeted SCFA brain metabolomics</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4933' rel='noopener noreferrer' target='_blank'><strong>MTBLS4933</strong></a>.</p><p><strong>Untargeted fecal metabolomics</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4932' rel='noopener noreferrer' target='_blank'><strong>MTBLS4932</strong></a>.</p>
Project description:To address whether ELF-MF influences the epigenetic landscape in differentiating haematopoietic cells, we performed an in vitro haematopoietic differentiation under powerline-simulating ELF-MF exposure (50 Hz, 1 mT, 5’ on/10’ off) in comparison to sham exposure (50 Hz, 7 µT, 5’ on/10’ off) or no exposure. We differentiated CD34+ cells (allcells, CB008F, lot: CBC121009M) isolated from human cord blood into the neutrophilic lineage, and performed ChIP combined with next generation sequencing for the histone modifications H3K4me2 and H3K27me3 before (t0) and after 5 days (t5) of differentiation. Genome-wide profiling of active and repressive histone modifications did not reveal significant alterations. However, ELF MF exposure has an influence on the robustness of the epigenetic landscape during global chromatin programming of granulopoiesis. Our data suggests that ELF MF has a stochastic effect on the epigenetic landscape of individual cells.
Project description:Micro-environment played an important role in the disease progression and overall survival. More recently, hypoxic signature were identified as one of the key signatures of innate anti-PD1 resistance, however, relatively little had been done to identify the key molecular signature of hypoxic response in melanoma and how these may correlated with other know signatures which correlate with poor prognosis. In this study we performed large scale study which integrate ChIP-seq of HIF (in one cell line) and RNA-seq (in three commonly used melanoma cell lines) to identify a common melanoma hypoxic signature. The finding were used to further integrated with our other genome wide which focus on MITF (the master regulator of the melanocyte lineage and a melanoma lineage oncogene, GSE77609) to elucidate the intricate interplay between MITF and HIF and how this interplay define a melanoma specific response to hypoxia.
Project description:The primary aim of this study was to evaluate the changes in hepatocyte gene expression under short-term hypoxic conditions in wild type and HIF-1a null cultures. To this end, hypoxia treated cultures were subjected to incubation with 1% O2/5% CO2/94% N2 at 37° C for eight hours prior to RNA isolation. Duplicate normoxic controls were established from separate animals wherein cultures were untreated and treated with Adbgal. Biological triplicates of wild type and HIF-1a null cultures were placed under hypoxic conditions and subsequently processed for microarray analysis. A total of 10 microarray hybridizations were performed.
Project description:This SuperSeries is composed of the following subset Series: GSE38839: MicroRNA expression profiling after short-term exposure to TCDD in zebrafish embryos [agilent and exiqon array data] GSE39808: MicroRNA expression profiling after short-term exposure to TCDD in zebrafish embryos [miRNA-Seq data] Refer to individual Series
Project description:To address whether ELF-MF influences the epigenetic landscape in the T cell lymphoma cell line Jurkat , we exposed Jurkat cells in the exponential growth phase to ELF MF or a sham control for 72 h, applying intermittently (5’ on/10’ off) a 50 Hz sine ELF-MF at a flux density of 1 mT. Additionally, cells were treated with the histone deacetylation inhibitor trichostatin A (TSA) at a subtoxic dose of 10 nM. Genome-wide profiling of active and repressive histone modifications did not reveal significant alterations. However, ELF-MF exposure has an influence on the robustness of the epigenetic landscape in leukaemic cells. Our data suggests that ELF-MF has a stochastic effect on the epigenetic landscape of individual cells.
Project description:Aspergillus fumigatus strains CEA10 and srbA mutant expression patterns were compared after exposure to 24h of hypoxic conditions Goal of this study was to find genes that are directly and/or indirectly regulated by the transcription factor srbA, that is know to be crucial for growth under hypoxic conditions Keywords: hypoxic stress response