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Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures

ABSTRACT: Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures

PROVIDER: PRJNA1102022 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28740067_1.fastq.gz	Fastqsanger.gz
	SRR28740067_2.fastq.gz	Fastqsanger.gz
	SRR28740068_1.fastq.gz	Fastqsanger.gz
	SRR28740068_2.fastq.gz	Fastqsanger.gz
	SRR28740069_1.fastq.gz	Fastqsanger.gz

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Investigation of parenteral nutrition-induced hepatotoxicity using human liver spheroid co-cultures

Project description:Parenteral nutrition (PN) is typically administered to individuals with gastrointestinal dysfunction, a contraindication for enteral feeding and a need for nutritional therapy. When PN is the only energy source in patients, it is defined as total parenteral nutrition (TPN). TPN is a life-saving approach for different patient populations, both in infants and adults. However, despite numerous benefits, TPN can cause adverse effects, including metabolic disorders and liver injury. TPN-associated liver injury, known as intestinal failure-associated liver disease (IFALD), represents a significant problem affecting up to 90% of individuals receiving TPN. IFALD pathogenesis is complex, depending on the TPN components as well as on the patient’s medical conditions. Despite numerous animal studies and clinical observations, the molecular mechanisms driving IFALD remain largely unknown. The present study was set up to elucidate the mechanisms underlying IFALD. For this purpose, human liver spheroid co-cultures were treated with TPN mixture followed by RNA sequencing analysis. It was found that prolonged exposure to TPN substantially changes the transcriptome profile of liver spheroids and affects multiple metabolic and signaling pathways contributing to liver injury.

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Project description:Preterm Yorkshire piglets were provided parenteral nutrition for 14 days and developed cholestasis and histologic liver injury. Bottle-fed age-matched controls were provided sow milk replacer every 2-3 hours for 14 days.

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Project description:We reported altered RNA expression profiles in wild-type (WT) C57BL/6J mice upon parenteral nutrition treatment compared to saline infusion controls. RNA samples used were isolated from the livers of PN or saline infused mice. RNA samples from 3 saline or 3 PN mouse livers were pooled, respectively. Final fold change were calculated by normalize the signal intensity of each probe in PN sample to that of the saline sample.

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