Corilagin alleviates LPS-induced sepsis through inhibiting pyroptosis via targeting TIR domain of MyD88 and binding CARD of ASC in macrophages.

Sepsis is a dysregulated systemic inflammatory response caused by infection that leads to multiple organ injury and high mortality without effective treatment. Corilagin, a natural polyphenol extracted from traditional Chinese herbs, exhibits strong anti-inflammatory properties. However, the role for Corilagin in lipopolysaccharide (LPS)-induced sepsis and the molecular mechanisms underlying this process have not been completely explored. Here we determine the effect of Corilagin on LPS-treated mice and use a screening approach integrating surface plasmon resonance with liquid chromatography-tandem mass spectrometry (SPR-LC-MS/MS) to further explore the therapeutic target of Corilagin. We discovered that Corilagin significantly prolonged the survival time of septic mice, attenuated the multi-organ injury and the expression of pyroptosis-related proteins in tissues of LPS-treated mice. In vitro studies revealed that Corilagin inhibited pyroptosis and NLRP3 inflammasome activation in LPS-treated macrophages followed with ATP stimulation, as reflected by decreased levels of GSDMD-NT and activated caspase-1, and reduced ASC specks formation. Mechanistically, Corilagin alleviated the formation of ASC specks and blocked the interaction of ASC and pro-caspase1 by competitively binding with the caspase recruitment domain (CARD) of ASC. Additionally, Corilagin interrupted the TLR4-MyD88 interaction through targeting TIR domain of MyD88, leading to the inhibition of NF-κB activation and NLRP3 production. In addition, Corilagin downregulated genes associated with several inflammatory responses and inflammasome-related signaling pathways in LPS-stimulated macrophages. Overall, our results indicate that the inhibitory effect of Corilagin on pyroptosis through targeting TIR domain of MyD88 and binding the CARD domain of ASC in macrophages plays an essential role in protection against LPS-induced sepsis.

A scoring model for diagnosis of tuberculous pleural effusion.

BACKGROUND: Due to the low efficiency of a single clinical feature or laboratory variable in the diagnosis of tuberculous pleural effusion (TBPE), the diagnosis of TBPE is still challenging. This study aimed to build a scoring diagnostic model based on laboratory variables and clinical features to differentiate TBPE from non-tuberculous pleural effusion (non-TBPE). METHODS: A retrospective study of 125 patients (63 with TBPE; 62 with non-TBPE) was undertaken. Univariate analysis was used to select the laboratory and clinical variables relevant to the model composition. The statistically different variables were selected to undergo binary logistic regression. Variables B coefficients were used to define a numerical score to calculate a scoring model. A receiver operating characteristic (ROC) curve was used to calculate the best cut-off value and evaluate the performance of the model. Finally, we add a validation cohort to verify the model. RESULTS: Six variables were selected in the scoring model: Age ≤ 46 years old (4.96 points), Male (2.44 points), No cancer (3.19 points), Positive T-cell Spot (T-SPOT) results (4.69 points), Adenosine Deaminase (ADA) ≥ 24.5U/L (2.48 point), C-reactive Protein (CRP) ≥ 52.8 mg/L (1.84 points). With a cut-off value of a total score of 11.038 points, the scoring model's sensitivity, specificity, and accuracy were 93.7%, 96.8%, and 99.2%, respectively. And the validation cohort confirms the model with the sensitivity, specificity, and accuracy of 92.9%, 93.3%, and 93.1%, respectively. CONCLUSION: The scoring model can be used in differentiating TBPE from non-TBPE.

Recent advances in bronchial thermoplasty for severe asthma: a narrative review.

Background and Objective: Severe asthma refers to asthma that requires step 4 or 5 therapy recommended by Global Initiative for Asthma (GINA) to prevent it from becoming uncontrolled or remaining "uncontrolled" despite this therapy. The poor treatment effect of severe asthma has been perplexing clinicians, which reduces the quality of life (QoL) of patients with asthma, and increases the mortality of such patients, so improving the therapeutic effect of severe asthma is an urgent problem to be solved in the clinic. Bronchial thermoplasty (BT) is a new non-drug therapy for severe asthma that is difficult to control with medications. It has been approved for clinical practice in China and the United States. The article aims at providing a new treatment option for patients with severe asthma that is poorly controlled by medications, thus improving the QoL in these patients. Methods: An extensive literature search was performed in the PubMed database, with "bronchial thermoplasty" as the key term. The full texts of all potentially relevant articles were obtained, and relevant information was extracted. Key Content and Findings: We find that BT is suitable for patients with severe asthma poorly controlled by medications. Conclusions: This paper reviews the mechanism of action, procedure, safety and effectiveness, adverse effects and complications, problems, and prospects of BT, with an attempt to guide the practical application of this technique.