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ABSTRACT: RNA sequencing of OA rats after Shaoyao Gancao Decoction treatment

PROVIDER: PRJNA795135 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17465554_1.fastq.gz	Fastqsanger.gz
	SRR17465554_2.fastq.gz	Fastqsanger.gz
	SRR17465555_1.fastq.gz	Fastqsanger.gz
	SRR17465555_2.fastq.gz	Fastqsanger.gz
	SRR17465556_1.fastq.gz	Fastqsanger.gz

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Project description:BACKGROUND: Diarrhea is common in infants, particularly, children less than 2 years old. Intractable or protracted infancy diarrhea is typically associated with feeding intolerance and malabsorption that is lethal for newborns. This study aimed to evaluate the effectiveness of baizhu shaoyao decoction in reducing functional diarrhea induced by weaning stress, while also delving into its potential mechanisms of action.RESULTS: Piglets were allocated into 5 groups, with each group receiving designated medication for a continuous 14-day period: control, zaohu powder, as well as low-, medium- and high-dose baizhu shaoyao decoction groups (n = 6 piglets per group). To identify diarrhea-related biomarkers, microbial communities, functions and metabolites were compared between the early-weaned piglets (control group) and those treated with 1.28 g/kg baizhu shaoyao decoction (medium-dose baizhu shaoyao decoction group). Our findings revealed significant shifts in microbial composition, function and metabolic profiles in piglets from the medium-dose baizhu shaoyao decoction group, intricately associated with the host's diarrhea status. Furthermore, carbohydrate metabolism and biosynthesis, lipid and amino acid metabolism, glycan activity and carbohydrate digestive enzymes exhibited downregulation in piglets of the medium-dose baizhu shaoyao decoction group compared to those in the control group. Transcriptome analysis highlighted the pivotal role of the FoxO1/3 transcription factor in mitigating weaning stress, particularly through the augmentation of CD4+/CD8+ T cell proportions. Our findings underscored that baizhu shaoyao decoction's therapeutic effects on weaning stress involve intestinal barrier restoration, modulation of brain-gut peptide expression and a reduction in mast-cell activity in the ileum.CONCLUSIONS: The key metabolites (chenodeoxycholyglycine, chenodeoxycholyltaurine, dinoprost, chenodeoxyglycocholic acid, glycochenodeoxycholic acid, glycocholic acid, N-choloylglycine, 5-trans-PGE2, Pregnanediol 3-O-glucuronide, spermidine and spermine) exhibited strong correlations with the abundance of Clostridia_bacterium and Lachnospiraceae_bacterium, emphasizing the significance of Clostridia_bacterium and Lachnospiraceae_bacterium in gut metabolism and function. Besides, this study suggests the potential efficacy of baizhu shaoyao decoction in addressing early post-weaning stress-induced diarrhea in infants, showcasing promising prospects for translational and clinical applications.

Project description:Abstract Objective: Osteoarthritis (OA) is accompanied by severe and debilitating pain that current analgesics are unable to fully alleviate. A multitude of signaling molecules, pathways, and cells have been identified as regulators of OA pain. Fatty acid binding protein 5 (FABP5) regulates pain in other disease states and we hypothesized that it is involved in the regulation of OA pain. Design: This was a combined clinical and pre-clinical study. Human synovial and osteochondral tissues collected during total knee arthroplasty were subjected to immunohistochemical analyses to identify the spatial expression patterns of FAB5, COX1, COX2, and macrophages. In addition, synovial specimens were cultured the presence and absence of SBFI-103, a selective FABP5 inhibitor, and cytokines and chemokines levels were measured. The rat monoiodoacetate (MIA) model of OA was then enlisted to evaluate the efficacy of SBFI-103 in alleviating OA pain. Finally, RNAseq was performed to identify alterations in synovial gene expression in vehicle and SBFI-103 treated MIA rats. Results: FABP5 expression was present in clinical OA tissues, with higher expression seen higher grade OA and no apparent differences between genders. Furthermore, FABP5 staining colocalized with CD14+ cells, indicating a macrophage origin of FABP5. Synovial specimens secreted CCL2, IL6, IL8, CXCL1, MIF, and Serpin E1 in vitro and treatment with SBFI-103 attenuated CCL2, IL6, IL8, and CXCL1, but not MIF and Serpin E1. Twenty-eight days after MIA injection, rats exhibited histological joint degradation and significant incapacitance. Ketoprofen treatment partially reduced incapacitance and naproxen had no effect; however, SBFI-103 showed a dose dependent alleviation of incapacitance that was independent of cannabinoid or PPARα receptor activity. RNAseq analyses identified differential expression of >6,000 transcripts compared to contralateral controls in vehicle treated rats and only 513 after SBFI-103 treatment. Notably, CCL2, CCL7, CCL9, and CXCL1were upregulated in vehicle treated rats, but not those treated with SBFI-103, and this was confirmed with qPCR. Conclusions: Our results show that FABP5 is upregulated in clinical and preclinical OA tissues and that its inhibition lowers pronociceptive signaling and reduces OA pain, indicating that FABP5 inhibitors may constitute a novel class of analgesics to treat OA.

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