Search

Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2‐mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell‐derived exosomes (AEC‐Exos), which potentially influence the development of asthma. However, the specific role of AEC‐Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC‐Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC‐Exos thorough transportation of hsa‐miR‐155‐5p–Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa‐miR‐155‐5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC‐Exos promote the enhanced Th2 inflammation through transportation of increased hsa‐miR‐155‐5p, which was mediated partly through SIRT1‐mediated pathway. hsa‐miR‐155‐5p is a potential biomarker for early prediction of acute asthma exacerbation. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a chronic inflammatory disease characterized by increased oxidative injury in vascular endothelial cells. Inhibiting the oxidative damage of vascular endothelial cells can effectively prevent the occurrence and development of AS. Of note, Genistein (GEN; ID no. 5280961) is phytochemical found in legume family which has flavonoid properties with multiple potential biological activities including antioxidant, anti-inflammatory and anticancer. Antioxidant capacity of GEN has a potential protective effect on vascular endothelial cells after oxidative stress. In the present study, the protective effect of GEN on H2O2-induced oxidation damage was investigated in human vascular endothelial cells (HUVECs). Following GEN pretreatment of HUVECs, H2O2 was added, and apoptosis was detected by flow cytometry, and the expression of relevant genes and proteins was detected by PCR and westerner blot. The results of the present study revealed that GEN significantly enhanced the cell survival rate and decreased the apoptotic rates of HUVECs after H2O2 stress. Besides, GEN reduced the accumulation of intracellular reactive oxygen species by enhancing activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD) and glutathione peroxidase. Moreover, GEN also inhibited the apoptosis of vascular endothelial cells and enhanced the activation of the nuclear factor erythroid2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/SOD pathway. Collectively, it was identified that GEN is an effective antioxidant which can reduce the oxidative damage by H2O2 through the Nrf2/HO-1/SOD signaling pathway in HUVECs. [ABSTRACT FROM AUTHOR]

Aging is characterized by a progressive loss of physiological integrity, leading to impaired organ function and, ultimately, increased vulnerability to death. Many complex diseases are related to aging, including asthma. In the lung, the airway epithelium serves as the first barrier to prevent the access of inspired external stimuli and dictates the initial stress responses. Notably, in the airway mucosa of asthma patients, an increase in senescent airway epithelial cells has been detected. Although it has been speculated that the senescence of airway epithelial cells could increase asthma susceptibility and aggravate asthma severity, the role of cell senescence in the development of asthma remains unclear. Integrin β4 (ITGB4) is a structural adhesion molecule with complex physiological functions that is downregulated in airway epithelial cells of asthma patients. This study demonstrates that the expression of ITGB4 in airway epithelial cells is downregulated significantly under oxidative stress or upon inflammatory stimulation. Moreover, we show that ITGB4 deficiency induces the senescence of airway epithelial cells through the activation of the p53 pathway both in vitro and in vivo. Together, our results demonstrate that airway epithelial senescence induced by ITGB4 deficiency after oxidative stress or inflammatory stimulation may be involved in the pathogenesis of asthma. Understanding the contribution of ITGB4 deficiency to the senescence of airway epithelial cells in asthma patients may provide new therapeutic approaches for the treatment of asthma. Aging is related to many diseases including asthma. Senescence of airway epithelial cells is increased in asthma patients. Here, it is demonstrated that ITGB4 expression in airway epithelia is downregulated under oxidative stress or inflammation stimulation. ITGB4 deficiency induces the senescence of airway epithelia by activating the p53 pathway. These results indicate that oxidative stress or inflammatory stimuli may contribute to the senescence of airway epithelia and could contribute to the pathogenesis of asthma. [ABSTRACT FROM AUTHOR]

Airway remodeling is a critical factor determining the pathogenesis and treatment sensitivity of severe asthma (SA) or uncontrolled asthma (UA). The activation of epithelial-mesenchymal trophic units (EMTUs) regulated by airway epithelial cells (AECs) has been proven to induce airway remodeling directly. However, the triggers for EMTU activation and the underlying mechanism of airway remodeling are not fully elucidated. Here, we screened the differentially expressed gene Cathepsin C (CTSC)/dipeptidyl peptidase 1 (DPP-1) in epithelia of SA and UA patients using RNA sequencing data and further verified the increased expression of CTSC in induced sputum of asthma patients which was positively correlated with the severity and airway remodeling. Moreover, direct instillation of exogenous CTSC induced airway remodeling. Genetic inhibition of CTSC suppressed EMTU activation and airway remodeling in two asthma models with airway remodeling. Mechanistically, increased secretion of CTSC from AECs induced EMTU activation through p38-mediated pathway, further inducing airway remodeling. Meanwhile, inhibition of CTSC also reduced the infiltration of inflammatory cells and the production of inflammatory factors in the lungs of asthmatic mice. Consequently, targeting CTSC with compound AZD7986 protected against airway inflammation, EMTU activation and remodeling in asthma model. Based on the dual effects of CTSC on airway inflammation and remodeling, CTSC is a potential biomarker and therapeutic target for SA or UA.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by increased oxidative injury in vascular endothelial cells. Inhibiting the oxidative damage of vascular endothelial cells can effectively prevent the occurrence and development of AS. Of note, Genistein (GEN; ID no. 5280961) is phytochemical found in legume family which has flavonoid properties with multiple potential biological activities including antioxidant, anti‑inflammatory and anticancer. Antioxidant capacity of GEN has a potential protective effect on vascular endothelial cells after oxidative stress. In the present study, the protective effect of GEN on H2O2‑induced oxidation damage was investigated in human vascular endothelial cells (HUVECs). Following GEN pretreatment of HUVECs, H2O2 was added, and apoptosis was detected by flow cytometry, and the expression of relevant genes and proteins was detected by PCR and westerner blot. The results of the present study revealed that GEN significantly enhanced the cell survival rate and decreased the apoptotic rates of HUVECs after H2O2 stress. Besides, GEN reduced the accumulation of intracellular reactive oxygen species by enhancing activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD) and glutathione peroxidase. Moreover, GEN also inhibited the apoptosis of vascular endothelial cells and enhanced the activation of the nuclear factor erythroid2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1)/SOD pathway. Collectively, it was identified that GEN is an effective antioxidant which can reduce the oxidative damage by H2O2 through the Nrf2/HO‑1/SOD signaling pathway in HUVECs.