Blood microRNA signatures serve as potential diagnostic biomarkers for hepatic sinusoidal obstruction syndrome caused by Gynura japonica containing pyrrolizidine alkaloids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA691466 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Background & Aims: Gynura japonica-induced hepatic sinusoidal obstruction syndrome (HSOS) is closely related with pyrrolizidine alkaloids (PAs) and the prevalence is on the rise worldwide in recent years. However, there is no effective therapy for PA-induced HSOS in clinic, which is partially caused by the failure of quick diagnosis. The aim of the present study was to identify blood miRNAs signatures as the potential biomarkers for PA-induced HSOS in clinic. Methods: Microarray-based miRNA profiling was performed on blood samples of the discovery cohort, i.e. 9 HSOS patients and 9 healthy donors. The differentially expressed miRNAs were further confirmed using a validation cohort of 20 independent HSOS patients. In addition, rat model was also established by orally administration of total alkaloids extract (TA) from G. japonica to investigate the association of miRNAs biomarkers with the progression of HSOS. Bioinformatic analysis, including GO and KEGG enrichment analyses, receiver operating characteristics curve (ROC) analysis, correlation analysis, etc., were conducted to evaluate the accuracy of the potential miRNA biomarkers. Results: Three miRNAs, namely miR-148a-3p, miR-362-5p, and miR-194-5p, were over-expressed in PA-induced HSOS patients and rats. They were positively related to the severity of liver injury and displayed considerable diagnostic accuracy for HSOS patients with areas under the curve (AUC) over 0.87. Conclusions: In summary, the present study demonstrated that 3 miRNAs, i.e. hsa-miR-148a-3p, hsa-miR-362-5p, and hsa-miR-194-5p, might serve as potential biomarkers for PA-induced HSOS in clinic. Conclusions: In summary, the present study demonstrated that 3 miRNAs, i.e. hsa-miR-148a-3p, hsa-miR-362-5p, and hsa-miR-194-5p, might serve as potential biomarkers for PA-induced HSOS in clinic.
2021-03-10 | GSE164635 | GEO
Project description:RNA-seq was employed to detect hepatic differential expression genes between pyrrolizidine alkaloids-induced liver injury mice and the untreated ones.
2021-04-13 | GSE171874 | GEO
Project description:Background and Aims: The Gynura japonica-induced hepatic sinusoidal obstruction syndrome (HSOS) is closely related to pyrrolizidine alkaloids (PAs), and its prevalence has been increasing worldwide in recent years. However, no effective therapy for PA-induced HSOS in clinics is available, partially due to the failure of quick diagnosis. This study aims to identify blood microRNA (miRNA) signatures as potential biomarkers for PA-induced HSOS in clinics. Methods: The microarray-based miRNA profiling was performed on blood samples of the discovery cohort, which consisted of nine patients with HSOS and nine healthy donors. Differentially expressed miRNAs were further confirmed using a validation cohort, which consisted of 20 independent patients with HSOS. In addition, the rat model was established through the oral administration of the total alkaloid extract from G. japonica to investigate the association of miRNA biomarkers with the progression of HSOS. Bioinformatic analyses, including GO and KEGG enrichment, receiver operating characteristics curve, and correlation analyses were conducted to evaluate the accuracy of the potential miRNA biomarkers. Results: Three miRNAs, namely miR-148a-3p, miR-362-5p, and miR-194-5p, were overexpressed in patients and rats with PA-induced HSOS. These miRNAs were positively related to the severity of liver injury and displayed considerable diagnostic accuracy for patients with HSOS with areas under the curve over 0.87. Conclusion: In summary, this study demonstrated that three miRNAs, hsa-miR-148a-3p, hsa-miR-362-5p, and hsa-miR-194-5p, might serve as potential biomarkers for PA-induced HSOS in clinics.
| S-EPMC7933570 | biostudies-literature
Project description:Recently, hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal preparations containing pyrrolizidine alkaloids (PAs), such as Gynura Rhizoma (Tusanqi), has gained global attention. However, the lack of a reliable and reproducible animal model has greatly hampered mechanistic studies. Therefore, we aimed to establish a reproducible HSOS mouse model and investigate the hepatotoxic mechanism. The model was established by intragastrical administration of Gynura Rhizoma extract, i.e., 1.0 g extract/kg per day (equal to 16.7 g crude drug/kg per day based on extraction rate and 49.1 mg PA/kg per day based on the total PA content in the extract determined) for 40 successive days. Then, the mice were sacrificed, and their blood samples and livers were collected for analyses. Using hematoxylin-eosin (HE) and Masson staining, scanning electron microscopy imaging, clinical biomarkers, and other assays, we showed that the HSOS was successfully induced in our mouse model. Furthermore, we detected the key factors involved in liver fibrosis in the mice, revealing significantly increased hydroxyproline concentration; elevated expression of α-smooth muscle actin (α-SMA) and fibrosis-related genes such as Collagen-1, Collagen-3, Mmp2, Mmp13, Timp1, Timp3, and Activin, upregulated Smad3 phosphorylation, and increased serum TGF-β levels. Moreover, pro-inflammatory cytokines, including Tnf-α, Il-1β, and Il-6, were also increased in the model. All these results demonstrate the key roles of the TGF-β-Smad3 and inflammatory signaling pathways in this Gynura Rhizoma-induced HSOS mouse model, suggesting that blockade of fibrosis and/or inflammation should be an effective treatment for HSOS.
| S-EPMC6786394 | biostudies-literature
Project description:Gynura divaricata (L.) DC. ,Gynura bicolor DC. ,Gynura pseudochina (L.) DC. and Gynura formosana Kitam. Raw sequence reads of their chloroplast genome
| PRJNA577159 | ENA
Project description:BackgroundThe intake of Gynura segetum, a traditional Chinese medicine, may be induce hepatic sinusoidal obstruction syndrome (HSOS). It has a high mortality rate based on the severity of the disease and the absence of therapeutic effectiveness. Therefore, the current study was designed to investigate the effects of bicyclol on HSOS induced by Gynura segetum and the potential molecular mechanisms.MethodsGynura segetum (30 g/kg) was administered for 4 weeks in the model group, while the bicyclol pretreatment group received bicyclol (200 mg/kg) administration. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (CHO), triglyceride (TG), and liver histological assays were detected to assess HSOS. The gene expressions of cytochrome P450 (CYP450) isozymes were quantified by real-time PCR. Moreover, hepatocellular apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, then apoptosis and autophagy-related markers were determined using Western blot.ResultsAs a result, bicyclol pretreatment is notably protected against Gynura segetum-induced HSOS, as observed by reducing serum ALT levels, inhibiting the reduction in CHO and TG levels, and alleviating the histopathological changes. Bicyclol pretreatment inhibited the changes in mRNA levels of CYP450 isozymes (including the increase in CYP2a5 and decrease in CYP2b10, 2c29, 2c37, 3a11, and 7b1). In addition, the upregulation of Bcl-2 and the downregulation of LC3-II/LC3-I proteins expression in HSOS were inhibited with bicyclol pretreatment.ConclusionBicyclol exerted a protective effect against HSOS induced by Gynura segetum, which could be attributed to the regulated expressions of CYP450 isozymes and alleviated the downregulation of autophagy.
| S-EPMC9757000 | biostudies-literature
Project description:Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS. This dataset is part of the TransQST collection.
2012-01-18 | E-MTAB-503 | biostudies-arrayexpress
Project description:Pyrrolizidine alkaloids (PAs) are secondary plant metabolites that can be found worldwide. They can have an impact to human health by inducing acute toxic effects like veno-occlusive disease in the liver and pulmonary arterial hypertension in the lung. The study focuses on the identification of gene expression changes in vivo in rat lungs after treatment with six structurally different PAs (echimidine, heliotrine, lasiocarpine, senecionine, senkirkine or platyphylline). Rats were treated by gavage daily with 3.3 mg/kg body weight PAs for 28 days. After this subacute exposure the transcriptional changes in the lung were investigated by whole genome microarray analysis. Transcriptomic analysis with six structurally different PA heliotrine, echimidine, lasiocarpine, senecionine, senkirkine, and platyphylline after subacute treatment of rats
2021-06-30 | GSE166195 | GEO