Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16202855_1.fastq.gz | Fastqsanger.gz | |||
| SRR16202855_2.fastq.gz | Fastqsanger.gz | |||
| SRR16202856_1.fastq.gz | Fastqsanger.gz | |||
| SRR16202856_2.fastq.gz | Fastqsanger.gz | |||
| SRR16202857_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Age-related macular degeneration (AMD) is a leading cause of blindness. Metabolic disorders and diets are risk factors. We compared lipid profiles and retinal phenotypes with long-term feeding of four diets in male Chinchilla rabbits. Animals were fed with normal diet (ND), high fat diet (HFD), high sucrose diet (HSD), or high-fat and high-sucrose diet (HFSD) for six months. The eyes were examined using multimodal imaging modalities and electroretinogram (ERG). Retinal sections were analyzed using H&E staining, toluidine blue staining, immunostaining, and transmission electron microscopy. Lipids and complement C3 in serum or aqueous humor were measured. RNA sequencing was performed to evaluate the retinal transcriptome changes. HFD and HSD had minor effects on lipid profiles but synergistically induced severe dyslipidemia. All diets did not cause obesity. HFSD induced reticular pseudo-drusen (RPD)-like lesions and pigmentary retinal abnormalities. The RPD-like lesions were mainly lipid droplets (retinosomes) in the RPE cells. HFSD induced elevated ocular C3 level and reduced retinal vessel branches, but not retinal inflammation. In conclusion, HFD and HSD can synergistically induce normal-weight dyslipidemia (NWD) and AMD-like retinal lesions. HFSD-fed male Chinchilla rabbits are a good model of early AMD and are valuable to studying NWD and retinosomes.
2024-09-05 | GSE276438 | GEO
Project description:Mutations in the metabolic enzyme fumarylacetoacetate hydrolase (FAH) cause hereditary tyrosinemia type I (HT1) in human. HT1 patients present acute and irreversible liver and kidney damage during infancy. CRISPR/Cas9-medated precise correction of disease-causing mutations in the liver of infant may provide a promising approach for the treatment of monogenetic liver metabolic disorders. However, to date, all previous precise gene therapy studies were conducted in adult HT1 rodent models (mice and rats), which are not able to recover irreversible pathological changes and result in less treatment effectiveness. In addition, rodent animals have very tiny livers comparing with that of humans, and HT1 rodent models do not authentically recapitulate some symptoms of human patients such as kidney damage. Therefore, to achieve the data which could be more translationable to medical practice of HT1 disease treatment by correcting gene mutation of hepatocytes, here, we chose a HT1 rabbit model, owning relatively large livers, and displaying liver and kidney damage as human patients, as the subject to test the gene therapy effectiveness starting from newborn stage. By delivery CRISPR/Cas9 system and donor templates to the livers by ear vein injection of adeno-associated virus (AAV), HT1 rabbits could be rescued the lethal phenotypes and were able to grow up to adult normally without NTBC treatment and give birth to offspring. In the livers of AAV-treated HT1 rabbits, both HDR-mediated and NHEJ-mediated gene corrections were occurred with the efficiencies ranged from 3.30% to 8.58%. Gene corrected HT1 rabbits showed normal structure and function of both livers and kidneys. This study in rabbits provides useful large-animal preclinical data to treat genetic metabolic disorders affecting the liver with gene therapy.
2019-12-31 | GSE142722 | GEO
Project description:Mutations in the metabolic enzyme fumarylacetoacetate hydrolase (FAH) cause hereditary tyrosinemia type I (HT1) in human. HT1 patients present acute and irreversible liver and kidney damage during infancy. CRISPR/Cas9-medated precise correction of disease-causing mutations in the liver of infant may provide a promising approach for the treatment of monogenetic liver metabolic disorders. However, to date, all previous precise gene therapy studies were conducted in adult HT1 rodent models (mice and rats), which are not able to recover irreversible pathological changes and result in less treatment effectiveness. In addition, rodent animals have very tiny livers comparing with that of humans, and HT1 rodent models do not authentically recapitulate some symptoms of human patients such as kidney damage. Therefore, to achieve the data which could be more translationable to medical practice of HT1 disease treatment by correcting gene mutation of hepatocytes, here, we chose a HT1 rabbit model, owning relatively large livers, and displaying liver and kidney damage as human patients, as the subject to test the gene therapy effectiveness starting from newborn stage. By delivery CRISPR/Cas9 system and donor templates to the livers by ear vein injection of adeno-associated virus (AAV), HT1 rabbits could be rescued the lethal phenotypes and were able to grow up to adult normally without NTBC treatment and give birth to offspring. In the livers of AAV-treated HT1 rabbits, both HDR-mediated and NHEJ-mediated gene corrections were occurred with the efficiencies ranged from 3.30% to 8.58%. Gene corrected HT1 rabbits showed normal structure and function of both livers and kidneys. This study in rabbits provides useful large-animal preclinical data to treat genetic metabolic disorders affecting the liver with gene therapy.
2019-12-31 | GSE142704 | GEO
Project description:Mutations in the metabolic enzyme fumarylacetoacetate hydrolase (FAH) cause hereditary tyrosinemia type I (HT1) in human. HT1 patients present acute and irreversible liver and kidney damage during infancy. CRISPR/Cas9-medated precise correction of disease-causing mutations in the liver of infant may provide a promising approach for the treatment of monogenetic liver metabolic disorders. However, to date, all previous precise gene therapy studies were conducted in adult HT1 rodent models (mice and rats), which are not able to recover irreversible pathological changes and result in less treatment effectiveness. In addition, rodent animals have very tiny livers comparing with that of humans, and HT1 rodent models do not authentically recapitulate some symptoms of human patients such as kidney damage. Therefore, to achieve the data which could be more translationable to medical practice of HT1 disease treatment by correcting gene mutation of hepatocytes, here, we chose a HT1 rabbit model, owning relatively large livers, and displaying liver and kidney damage as human patients, as the subject to test the gene therapy effectiveness starting from newborn stage. By delivery CRISPR/Cas9 system and donor templates to the livers by ear vein injection of adeno-associated virus (AAV), HT1 rabbits could be rescued the lethal phenotypes and were able to grow up to adult normally without NTBC treatment and give birth to offspring. In the livers of AAV-treated HT1 rabbits, both HDR-mediated and NHEJ-mediated gene corrections were occurred with the efficiencies ranged from 3.30% to 8.58%. Gene corrected HT1 rabbits showed normal structure and function of both livers and kidneys. This study in rabbits provides useful large-animal preclinical data to treat genetic metabolic disorders affecting the liver with gene therapy.
2019-12-31 | GSE142721 | GEO
Project description:Inhibition of AMPK is tightly associated with metabolic perturbations upon over nutrition, yet the molecular mechanism underneath that is not clear. Here, we demonstrate serine/threonine-protein phosphatase 6 regulatory subunit 3, SAPS3, is a negative regulator of AMPK. SAPS3 is induced under high fat diet (HFD) and recruits the PP6 catalytic subunit to deactivate phosphorylated-AMPK, thereby inhibiting AMPK-controlled metabolic pathways. Either whole-body or liver-specific deletion of SAPS3 protects male mice against the HFD-induced detrimental consequences and reverses HFD-induced metabolic and transcriptional alterations while loss of SAPS3 has no effects on mice under balanced diets. Furthermore, genetic inhibition of AMPK is sufficient to block the protective phenotype in SAPS3 knockout male mice under HFD. Together, our results reveal that SAPS3 is a negative regulator of AMPK and suppression of SAPS3 functions as a guardian when metabolism is perturbed and represents a potential therapeutic strategy to treat metabolic syndromes.
2023-01-26 | PXD039625 | Pride
Project description:Mutations in the metabolic enzyme fumarylacetoacetate hydrolase (FAH) cause hereditary tyrosinemia type I (HT1) in human. HT1 patients present acute and irreversible liver and kidney damage during infancy. CRISPR/Cas9-medated precise correction of disease-causing mutations in the liver of infant may provide a promising approach for the treatment of monogenetic liver metabolic disorders. However, to date, all previous precise gene therapy studies were conducted in adult HT1 rodent models (mice and rats), which are not able to recover irreversible pathological changes and result in less treatment effectiveness. In addition, rodent animals have very tiny livers comparing with that of humans, and HT1 rodent models do not authentically recapitulate some symptoms of human patients such as kidney damage. Therefore, to achieve the data which could be more translationable to medical practice of HT1 disease treatment by correcting gene mutation of hepatocytes, here, we chose a HT1 rabbit model, owning relatively large livers, and displaying liver and kidney damage as human patients, as the subject to test the gene therapy effectiveness starting from newborn stage. By delivery CRISPR/Cas9 system and donor templates to the livers by ear vein injection of adeno-associated virus (AAV), HT1 rabbits could be rescued the lethal phenotypes and were able to grow up to adult normally without NTBC treatment and give birth to offspring. In the livers of AAV-treated HT1 rabbits, both HDR-mediated and NHEJ-mediated gene corrections were occurred with the efficiencies ranged from 3.30% to 8.58%. Gene corrected HT1 rabbits showed normal structure and function of both livers and kidneys. This study in rabbits provides useful large-animal preclinical data to treat genetic metabolic disorders affecting the liver with gene therapy.
2019-12-31 | GSE142782 | GEO
Project description:Inhibition of AMPK is tightly associated with metabolic perturbations upon over nutrition, yet the molecular mechanism underneath that is not clear. Here, we demonstrate serine/threonine-protein phosphatase 6 regulatory subunit 3, SAPS3, is an essential negative regulator of AMPK. SAPS3 is induced under high fat diet (HFD) and recruits the PP6 catalytic subunit to deactivate phosphorylated-AMPK, thereby inhibiting AMPK-controlled metabolic pathways. Remarkably, either whole-body or liver-specific deletion of SAPS3 protects mice against the HFD-induced detrimental consequences and reverses HFD-induced metabolic and transcriptional alterations while loss of SAPS3 has no effects on mice under balanced diets. Furthermore, genetic inhibition of AMPK is sufficient to block the protective phenotype in SAPS3 knockout mice under HFD. Together, our results reveal that SAPS3 is a critical negative regulator of AMPK and suppression of SAPS3 functions as a guardian when metabolism is perturbed and represents a potential therapeutic strategy to treat metabolic syndromes.
2023-01-18 | GSE210333 | GEO
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5â halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of âepigenetic carrierâ that mediate intergenerational inheritance of acquired traits. Mature sperm small-RNA profiles between High-fat-diet (HFD) and Normal-diet (ND) males; Transcriptional profiles of 8-cell embryos and balstocysts that developed from zygotes that injected with sperm RNAs from HFD vs ND males. Transcriptional profiles and RRBS profiles of islets of F1 offsrping that generated from zygotes that injected with sperm RNAs from HFD vs ND males.
2015-12-31 | E-GEOD-75544 | biostudies-arrayexpress
Project description:Infection with hepatitis E virus (HEV) represents a global problem, with over 20 million people infected annually. No specific antiviral drugs are available for treating HEV infection, necessitating the development of novel targeted therapeutics. Here, we report that the N-methyl-D-aspartate receptor (NMDAR) antagonist ifenprodil, a clinically approved drug used to treat idiopathic pulmonary fibrosis (IPF), is an HEV inhibitor in liver-derived cells. In vitro investigation demonstrates that ifenprodil suppresses viral protein expression in a dose-dependent manner in human hepatoma cells by inhibiting early stages of viral infection. We also found that ifenprodil modulates host cell intrinsic biological processes distinct from virus-induced innate immunity, inhibiting HEV RNA accumulation in primary human hepatocytes. Finally, the inhibitory effect of ifenprodil in vivo was also tested in rabbits challenged with the HEV-3ra CHN-BJ-R14 strain. Fecal virus shedding was below the limit of detection in two animals for both ribavirin-treated and ifenprodil-treated rabbits compared to vehicle-treated control animals. Our data demonstrate that ifenprodil is an effective anti-HEV compound with potential as a therapeutic candidate for the treatment of HEV infection.
2024-09-30 | GSE274780 | GEO