Tenuifolin is an effective compound from tenuigenin. We believe that this finding should lead the way for future experiments to determine the exact mechanism for tenuifolin's effect on Abeta secretion.

Edited by Xiao-Fan Wang Asthma is thought to be caused by malfunction of type 2 T helper cell (Th2)-mediated immunity, causing excessive inflammation, mucus overproduction, and apoptosis of airway epithelial cells. Heme oxygenase-1 (HO-1) functions in heme catabolism and is both cytoprotective and anti-inflammatory. We hypothesized that this dual function may be related to asthma's etiology. Using primary airway epithelial cells (pAECs) and an asthma mouse model, we demonstrate that severe lung inflammation is associated with rapid pAEC apoptosis. Surprisingly, NOD-like receptor protein 3 (NLRP3) inhibition, retinoid X receptor (RXR) deficiency, and HO-1 induction were associated with abrogated apoptosis. MCC950, a selective small-molecule inhibitor of canonical and noncanonical NLRP3 activation, reduced RXR expression, leading to decreased pAEC apoptosis that was reversed by the RXR agonist adapalene. Of note, HO-1 induction in a mouse model of ovalbumin-induced eosinophilic asthma suppressed Th2 responses and reduced apoptosis of pulmonary pAECs. In vitro, HO-1 induction desensitized cultured pAECs to ovalbumin-induced apoptosis, confirming the in vivo observations. Critically, the HO-1 products carbon monoxide and bilirubin suppressed the NLRP3-RXR axis in pAECs. Furthermore, HO-1 impaired production of NLRP3-RXR-induced cytokines (interleukin [IL]-25, IL-33, thymic stromal lymphopoietin, and granulocyte-macrophage colony-stimulating factor) in pAECs and lungs. Finally, we demonstrate that HO-1 binds to the NACHT domain of NLRP3 and the RXR␣ and RXR␤ subunits and that this binding is not reversed by Sn-protoporphyrin. Our findings indicate that HO-1 and its products are essential for pAEC survival to maintain airway epithelium homeostasis during NLRP3-RXRmediated apoptosis and inflammation.

Epithelial cells (ECs)‐derived cytokines are induced by different stimuli through pattern recognition receptors (PRRs) to mount a type‐2‐cell‐mediated immune response; however, the underlying mechanisms are poorly characterized. Here, we demonstrated asthmatic features in both primary bronchial epithelial cells (pBECs) and mouse model using several allergens including ovalbumin (OVA), house dust mite (HDM), or Alternaria alternata. We found that toll‐like receptor 2 (TLR2) was highly induced in ECs but not dendritic cells (DCs) by various allergens, leading to recruitment of circulating basophils into the lung via C‐C chemokine ligand‐2 (CCL2). TLR2 expression increased thymic stromal lymphopoietin (TSLP) production through the NF‐κB and JNK signaling pathways to extend the survival of recruited basophils and resident DCs in the lung, predisposing a type‐2‐cell‐mediated airway inflammation. Conversely, TLR2 deficiency impaired http://secretion of TSLP and CCL2, decreased infiltration of lung basophils, and increased resistance to Th2 response. Blocking TSLP also phenocopied these phenomena. Our findings reveal a pro‐inflammatory role of airway ECs through a TLR2‐dependent TSLP production, which may have implication for treating allergic asthma.

Our data suggest that HO-1 exerts its inhibitory effect on Th17 cell differentiation by directly associating and blocking STAT3 phosphorylation. We speculate that hemin may be a potential therapeutic candidate for the treatment of other types of immune and pulmonary inflammatory-related diseases.

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Alzheimer's disease (AD) is a progressively neurodegenerative disease characterized by cognitive deficits and alteration of personality and behavior. As yet, there is no efficient treatment for AD. 5HT2A receptor (5HT2AR) is a subtype of 5HT2 receptor belonging to the serotonin receptor family, and its antagonists have been clinically used as antipsychotics to relieve psychopathy. Here, we discovered that clinically first‐line antiallergic drug desloratadine (DLT) functioned as a selective antagonist of 5HT2AR and efficiently ameliorated pathology of APP/PS1 mice. The underlying mechanism has been intensively investigated by assay against APP/PS1 mice with selective 5HT2AR knockdown in the brain treated by adeno‐associated virus (AAV)‐ePHP‐si‐5HT2AR. DLT reduced amyloid plaque deposition by promoting microglial Aβ phagocytosis and degradation, and ameliorated innate immune response by polarizing microglia to an anti‐inflammatory phenotype. It stimulated autophagy process and repressed neuroinflammation through 5HT2AR/cAMP/PKA/CREB/Sirt1 pathway, and activated glucocorticoid receptor (GR) nuclear translocation to upregulate the transcriptions of phagocytic receptors TLR2 and TLR4 in response to microglial phagocytosis stimulation. Together, our work has highly supported that 5HT2AR antagonism might be a promising therapeutic strategy for AD and highlighted the potential of DLT in the treatment of this disease.

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer worldwide. However, operative diagnostic and prognostic systems for ESCC remain to be established. To improve assessment of the prognosis for patients with ESCC, the present study developed an online consensus survival tool for ESCC, termed OSescc. OSescc was built using 264 ESCC cases with gene expression data and relevant clinical information obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Kaplan-Meier survival plots with hazard ratios and P-values were generated by OSescc to predict the association between potential biomarkers and relapse free survival and overall survival. In addition, the current study integrated a function by which one could assess the prognosis based on an individual probe or the mean value of multiple probes for each gene, which helped improve the evaluation of the validity and reliability of the potential prognosis biomarkers. OSescc can be accessed at .

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