Project description:Resistant starches (RS), fed as high amylose maize starch (HAMS) or butyrylated HAMS (HAMSB), oppose dietary protein-induced colonocyte DNA damage in rats. In this study, rats were fed diets high in fat (19%) and protein (20%) with different forms of digestible starch (low amylose maize starch (LAMS) or low amylose whole wheat (LAW)) or RS (HAMS, HAMSB, or a whole high amylose wheat (HAW) generated by RNA interference (RNAi)) for 11 wk. A control diet contained 7% fat, 13% protein and LAMS. The aim of this study was to detect changes in the expression of DNA damage and repair genes in response to the above dietary treatments.
Project description:ε-poly-L-lysine (ε-PL) is a high value, widely used natural antimicrobial peptide additive for foods and cosmetic products that is mainly produced by S. albulus. In previous work, we developed the high-yield industrial strain S. albulus WG-608 through successive rounds of engineering. Here, we use integrated physiological, transcriptomic, and proteomics association analysis to resolve the complex mechanisms underlying high ε-PL production by comparing WG-608 with the progenitor strain M-Z18. Our results show that key genes in the glycolysis, glyoxylate, and L-lysine biosynthesis pathways are differentially upregulated in WG-608, while genes in the biosynthetic pathways for fatty acids, various branched amino acids, and secondary metabolite by-products are downregulated. This regulatory pattern results in the introduction of more carbon atoms into L-lysine biosynthesis and ε-PL production. Furthermore, transcriptional and translational upregulation of genes involved in the tricarboxylic acid cycle, oxidative phosphorylation, and pentose phosphate pathway also increase the pools of available NADH, ATP, and NADPH. In addition, significant changes in the regulation of DNA replication, transcription, and translation, two component systems, and quorum sensing may facilitate the adaptability to environmental pressure, thus further regulating the ε-PL biosynthesis. This study enables comprehensive understanding of the biosynthetic mechanisms of ε-PL in S. albulus WG-608, while providing a theoretical foundation development of advanced Streptomycetaceae microbial cell factories.
Project description:Wegener’s granulomatosis (WG) is a systemic inflammatory disease that can lead to substantial morbidity. This study seeks to further understanding of the biology underlying WG, and to discover markers of disease activity useful in prognosis and treatment guidance.
Project description:Senescence, a stable state of growth arrest, affects many physiological and pathophysiological processes, especially aging. Previous work has indicated that transcription factors (TFs) play a role in regulating senescence. However, a systematic study of regulatory TFs during replicative senescence (RS) using multi-omics analysis is still lacking. Here, we generated time-resolved RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets during RS of mouse skin fibroblasts, which demonstrated that an enhanced inflammatory response and reduced proliferative capacity were the main characteristics of RS in both the transcriptome and epigenome. Through integrative analysis and genetic manipulation, we found that transcription factors E2F4, TEAD1 and AP-1 are key regulators of RS. Overexpression of E2f4 improved cellular proliferative capacity, attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites (DMSs). Moreover, knockdown of Tead1 attenuated SA-β-Gal activity and partially altered the RS-associated transcriptome. In addition, knockdown of Atf3, one member of AP-1 superfamily TFs, reduced Cdkn2a (P16) expression in pre-senescent fibroblasts. Taken together, results of this study identified transcription factors regulating the senescence program through multi-omics analysis, providing potential therapeutic targets for anti-aging.
Project description:In the present study, we designed a 7-week rat model, consuming high-fat diet or heat-misture-treated high fat diet. The liver was used for microarray analyses. Transcriptome profiling reveal that high-fat diet with or with out heat-moisture treatment induced different transcriptome changes, mainly on lipid metabolism and inflammation.
Project description:Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). While RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the pre-existing CLL, mechanisms leading to RS have not been clarified yet. To better understand the pathogenesis of RS, we analyzed a series of cases including: 59 RS, 28 CLL-phase of RS, 315 CLL and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL-phase, being present in approximately half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. While RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL-phase preceding RS had not a generalized increase in genomic complexity when compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.
Project description:Metabolic Syndrome (MetS) is a strong predictor for diabetes and cardiovascular disease and is defined by a constellation of phenotypes including increased and adverse body fat distribution, insulin resistance, abnormalities in lipids and lipoproteins, malfunctional cardiovascular performance, and abnormal levels of adipokines and cytokines. We assayed in a subset of our family cohort phentoyped for MetS phentoypes, the genome-wde transcript levels using the Illumina Human WG-6 v3 expression arrays.
Project description:Metabolic Syndrome (MetS) is a strong predictor for diabetes and cardiovascular disease and is defined by a constellation of phenotypes including increased and adverse body fat distribution, insulin resistance, abnormalities in lipids and lipoproteins, malfunctional cardiovascular performance, and abnormal levels of adipokines and cytokines. We assayed in a subset of our family cohort phentoyped for MetS phentoypes, the genome-wde transcript levels using the Illumina Human WG-6 v2 expression arrays.
Project description:Purpose: Many young adults are in a state of stress due to social and psychological pressures, which may result in male reproductive dysfunction. To provide new insight into this phenomenon, we investigated the relationship between pathological changes in rat spermatogenic cells and the expression of genes specific to spermatogenic cell types under different stress conditions. Methods: After establishing rat stress models of different time durations, we observed pathological changes in testicular tissues through haematoxylin and eosin staining, and analysed gene expression in spermatogenic cells by RNA-seq, bioinformatic analysis, and reverse transcription qPCR (RT-qPCR).Three testicular samples were taken from each group to construct 12 cDNA libraries. For each sample, 3 μg RNA was used as the starting material. Ribosomal RNA was removed using the Epicentre Ribo-Zero™ Gold kit (Rat) (Epicentre, an Illumina company, Madison, WI, USA). Results:Compared with the control group, there were 1,194 DEGs in the 3-day RS+IS group , including 455 upregulated genes and 739 downregulated genes , 1,774 DEGs in the 14-day RS+IS group including 1,124 upregulated genes and 650 downregulated genes, and 2,267 DEGs in the 21-day RS+IS group including 1,366 upregulated genes and 901 downregulated genes. Mean-while, some same expression patterns were observed in three phenotypes.After comparison with single-cell sequencing data, 349 DEGs of spermatogenic cells at different developmental stages were found. Conclusions: Our study suggest that chronic psychosomatic stress can affect the spermatogenic transcriptome of the testes, leading to a significant change in the expression of the spermatogenic genes. At the same time, histopathological and immunohistochemical results showed that chronic stress may lead to pathological changes in spermatogenic cells and to a significant decrease in key regulatory proteins