Xijiao Dihuang decoction protects against sepsis-induced cardiac dysfunction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA891339 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21935471_1.fastq.gz | Fastqsanger.gz | |||
| SRR21935471_2.fastq.gz | Fastqsanger.gz | |||
| SRR21935472_1.fastq.gz | Fastqsanger.gz | |||
| SRR21935472_2.fastq.gz | Fastqsanger.gz | |||
| SRR21935473_1.fastq.gz | Fastqsanger.gz |
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Project description:The goals of this study is to identify the differential expressed genes in heart of C57BL/6 mice with or without LPS treatment, and compare the differential expressed genes in the heart of LPS injection C57BL/6 mice after Xijiao Dihuang decoction(XJDHT) treatment. Briefly, the mice were randomly divided into 3 groups: control, LPS and LPS + XJDHT groups (n=4 for each group). Mice in Control and LPS groups were intraperitoneal injection with saline and 10mg/kg of LPS respectively, and orally administrated with saline; the mice in LPS + XJDHT groups were intraperitoneal injection with LPS (10 mg/kg) and orally administrated with 50 mg/kg /day of XJDHT for total 3 days. Then the heart were used to identify differentially expressed genes among different groups.
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Project description:Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and improved viral infection-induced mouse weight loss but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction both dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection. Screening and profiling of known plant microRNA in HS and HS decoction
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Project description:Despite intensive research and constant medical progress, sepsis remains one of the most urgent unmet medical needs of today. Most studies have been focused on the inflammatory component of the disease, however, recent advances support the notion that sepsis is accompanied by extensive metabolic perturbations. During times of limited caloric intake and high energy needs, the liver acts as the central metabolic hub in which PPARa is crucial to coordinate the breakdown of fatty acids. The role of hepatic PPARa in liver dysfunction during sepsis has hardly been explored. We demonstrate that sepsis leads to a starvation response that is hindered by the rapid decline of hepatic PPARa levels, causing excess free fatty acids, leading to lipotoxicity, and glycerol. In addition, treatment of mice with the PPARa agonist pemafibrate protects against bacterial sepsis by improving hepatic PPARa function, reducing lipotoxicity and tissue damage. Since lipolysis is also increased in sepsis patients and pemafibrate protects after the onset of sepsis, these findings may point towards new therapeutic leads in sepsis.
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Project description:<h4><strong>INTRODUCTION:</strong> Sepsis is intricately linked to intestinal damage and barrier dysfunction. At present times, there is a growing interest in a metabolite-based therapy for multiple diseases.</h4><p><strong>METHODS:</strong> Serum samples from septic patients and healthy individuals were collected and their metabonomics profiling assessed using Ultra-Performance Liquid Chromatography-Time of Flight Mass Spectrometry (UPLC-TOFMS). The eXtreme Gradient Boosting algorithms (XGBOOST) method was used to screen essential metabolites associated with sepsis, and five machine learning models, including Logistic Regression, XGBoost, GaussianNB(GNB), upport vector machines(SVM) and RandomForest were constructed to distinguish sepsis including a training set (75%) and validation set(25%). The area under the receiver-operating characteristic curve (AUROC) and Brier scores were used to compare the prediction performances of different models. Pearson analysis was used to analysis the relationship between the metabolites and the severity of sepsis. Both cellular and animal models were used to HYPERLINK 'javascript:;' assess the function of the metabolites.</p><p><strong>RESULTS:</strong> The occurrence of sepsis involve metabolite dysregulation. The metabolites mannose-6-phosphate and sphinganine as the optimal sepsis-related variables screened by XGBOOST algorithm. The XGBoost model (AUROC=0.956) has the most stable performance to establish diagnostic model among the five machine learning methods. The SHapley Additive exPlanations (SHAP) package was used to interpret the XGBOOST model. Pearson analysis reinforced the expression of Sphinganine, Mannose 6-phosphate were positively associated with the APACHE-II, PCT, WBC, CRP and IL-6. We also demonstrated that sphinganine strongly diminished the LDH content in LPS-treated Caco-2 cells. In addition, using both <em>in vitro</em> and <em>in vivo</em> examination, we revealed that sphinganine strongly protects against sepsis-induced intestinal barrier injury.</p><p><strong>DISCUSSION:</strong> These findings highlighted the potential diagnostic value of the ML, and also provided new insight into enhanced therapy and/or preventative measures against sepsis.</p>
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