Metagenomic and metabolomic analyses show correlations between intestinal microbiome diversity and microbiome metabolites in ob/ob and ApoE−/− mice DOI Creative Commons
Sashuang Dong, Chengwei Wu, Wencan He

et al.

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Oct. 13, 2022

Obesity and atherosclerosis are the most prevalent metabolic diseases. ApoE-/- ob/ob mice widely used as models to study pathogenesis of these However, how gut microbes, bacteriophages, metabolites change in two disease is unclear. Here, we wild-type C57BL/6J (Wt) normal controls analyze intestinal archaea, bacteria, microbial through metagenomics metabolomics. Analysis archaea showed that abundances Methanobrevibacter Halolamina were significantly increased decreased, respectively, group compared with those Wt groups (p < 0.05). Compared group, relative bacterial genera Enterorhabdus, Alistipes, Bacteroides, Prevotella, Rikenella, Barnesiella, Porphyromonas, Riemerella, Bifidobacterium decreased 0.05) mice, abundance Akkermansia was group. The A. muciniphila L. murinus increased, Lactobacillus_ prophage_ Lj965 Lactobacillus _ prophage Lj771 more abundant than mice. aminoacyl-tRNA biosynthesis pathway revealed enriched compounds phenylalanine, glutamine, glycine, serine, methionine, valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, tyrosine downregulated Aminoacyl-tRNA synthetases considered manifestations diseases closely associated obesity, atherosclerosis, type 2 diabetes. These data offer new insight regarding possible causes provide a foundation for studying regulation various food nutrients models.

Language: Английский

Mutations in DARS2 result in global dysregulation of mRNA metabolism and splicing DOI Creative Commons
Shouhong Guang,

B. M. O’Brien,

Albert S. Fine

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Aug. 10, 2023

Abstract Leukoencephalopathy with brainstem and spinal cord involvement lactate elevation (LBSL) is a rare neurological disorder caused by the mutations in DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase. The objective of this study was to understand impact on cell processes through evaluation LBSL patient stem derived cerebral organoids neurons. We generated human (hCOs) from induced pluripotent cells (iPSCs) seven patients three healthy controls using an unguided protocol. Single 70-day-old hCOs were subjected SMART-seq2 sequencing bioinformatic analysis acquire high-resolution gene transcript expression datasets. Global demonstrated dysregulation number genes involved mRNA metabolism splicing within hCOs. Importantly, there distinct divergent profiles based nature mutation. At level, pervasive differential usage spliced exon events that are protein translation identified Single-cell (exon 3) showed some exclusively express transcripts lacking 3, indicating not all can benefit “leaky” common splice site mutations. gene- transcript-level, we uncovered dysregulated RNA splicing, may underlie at least pathophysiological mechanisms LBSL. To confirm hCO findings, iPSC-derived neurons (iNs) overexpressing Neurogenin 2 lentiviral vector neuronal growth, 3 expression. Live imaging revealed growth defects iNs, consistent finding downregulated related differentiation iNs compared iPSCs, increased exclusion 3. scope complexity our data imply potentially transcription regulation beyond its canonical role aminoacylation. Nevertheless, work highlights transcript-level as critical, relatively unexplored, mechanism linking genetic neurodegenerative disorders.

Language: Английский

Citations

4
Doxorubicin-Induced Cardiotoxicity May Be Alleviated by Bone Marrow Mesenchymal Stem Cell-Derived Exosomal lncRNA via Inhibiting Inflammation DOI Creative Commons
Chao Tian, Yanyan Yang, Bing Li

et al.

Journal of Inflammation Research, Journal Year: 2022, Volume and Issue: Volume 15, P. 4467 - 4486

Published: Aug. 1, 2022

To explore the therapeutic mechanism of bone marrow mesenchymal stem cells derived exosomes (BMSC-Exos) for doxorubicin (DOX)-induced cardiotoxicity (DIC) and identify long noncoding RNAs' (lncRNAs') anti-inflammation function by BMSC-Exos.High-throughput sequencing transcriptome bioinformatics analysis lncRNA were performed between DOX group BEC (bone coculture) group. Elevated (ElncRNA) in cardiomyocytes compared with confirmed. Based on location co-expression relationship ElncRNA its target genes, we predicted two genes ElncRNA, named cis_targets trans_targets. The analyzed enrichment analyses. Then, identified key cellular biological pathways regulating DIC. Experiments to verify effects origin lncRNAs vitro vivo.Three hundred one differentially expressed groups (fold change >1.5 p < 0.05), which 169 elevated GO ElncRNAs showed that they predominantly involved inflammation-associated processes. KEGG indicated their regulatory mainly oxidative stress-induced inflammation proliferation cardiomyocyte. verification experiments stress cell deaths decreased groups. Moreover, from top 10 results, MSTRG.98097.4 MSTRG.58791.2 both While vivo, only expression is consistent result vitro.Our results show MSTRG.58791.2, possibly secreted BMSC-Exos able alleviate DIC suppressing inflammatory response inflammation-related death.

Language: Английский

Citations

7
Serine mistranslation induces the integrated stress response without accumulation of uncharged tRNAs DOI Creative Commons
Hong Zhang, Jiqiang Ling

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

Abstract Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that support robust and accurate protein synthesis. A rapidly expanding number of studies show mutations in aaRSs lead to multiple human diseases, including neurological disorders cancer. Much remains unknown about how aaRS impact health. In particular, aminoacylation errors affect stress responses fitness eukaryotic cells poorly understood. The integrated response (ISR) is an adaptive mechanism stresses. However, chronic activation the ISR contributes development diseases (e.g., neuropathies). Here we Ser misincorporation into Ala Thr codons, resulting from editing defects or tRNAs, constitutively active ISR. Such does not appear depend on accumulation uncharged implicating mistranslation may ribosome stalling collision.

Language: Английский

Citations

1
Mitochondrial dysfunction in lipid processing and gastrointestinal disorders DOI
Yan Hu, Hao Huang, Rong Xiang

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(5), P. 364 - 366

Published: Feb. 27, 2024

Language: Английский

Citations

1
Metagenomic and metabolomic analyses show correlations between intestinal microbiome diversity and microbiome metabolites in ob/ob and ApoE−/− mice DOI Creative Commons
Sashuang Dong, Chengwei Wu, Wencan He

et al.

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Oct. 13, 2022

Obesity and atherosclerosis are the most prevalent metabolic diseases. ApoE-/- ob/ob mice widely used as models to study pathogenesis of these However, how gut microbes, bacteriophages, metabolites change in two disease is unclear. Here, we wild-type C57BL/6J (Wt) normal controls analyze intestinal archaea, bacteria, microbial through metagenomics metabolomics. Analysis archaea showed that abundances Methanobrevibacter Halolamina were significantly increased decreased, respectively, group compared with those Wt groups (p < 0.05). Compared group, relative bacterial genera Enterorhabdus, Alistipes, Bacteroides, Prevotella, Rikenella, Barnesiella, Porphyromonas, Riemerella, Bifidobacterium decreased 0.05) mice, abundance Akkermansia was group. The A. muciniphila L. murinus increased, Lactobacillus_ prophage_ Lj965 Lactobacillus _ prophage Lj771 more abundant than mice. aminoacyl-tRNA biosynthesis pathway revealed enriched compounds phenylalanine, glutamine, glycine, serine, methionine, valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, tyrosine downregulated Aminoacyl-tRNA synthetases considered manifestations diseases closely associated obesity, atherosclerosis, type 2 diabetes. These data offer new insight regarding possible causes provide a foundation for studying regulation various food nutrients models.

Language: Английский

Citations

6