Caspase-3/GSDME dependent pyroptosis contributes to offspring lung injury induced by gestational PFOS exposure via PERK/ATF4 signaling.

Perfluorooctane sulfonate (PFOS) is widely used in industry and consumer products. Previous studies have showed that PFOS gestational exposure is associated with offspring lung damage in rat. However, the underlying mechanisms remain poorly understood. In this study, we investigated the role of gasdermin E (GSDME) in lung injury of offspring and its underlying mechanisms using in vivo and in vitro approaches. Pregnant SD rats were exposed to PFOS (1 mg/kg BW/d) between gestational day 12-18, and the lung tissue of the offspring was evaluated on postnatal day 7. PFOS treated animals exhibited alveolar septal thickening and inflammation-related damages, with an increased expression of GSDME in alveolar type II epithelial cells (AECII). Furthermore, in vitro experiments demonstrated that PFOS exposure (with 225 µM and up) upregulated the caspase-3/GSDME signaling pathway in AECII. Also, ultrastructure analysis revealed significant changes in the endoplasmic reticulum (ER) structure in PFOS-induced pyroptotic cells, which is consistent with the ER stress detected in these cells. Additionally, PFOS exposure led to increased expression of ER stress-related proteins, including p-PERK, p-eIF2α, ATF4, and CHOP. Subsequently, using specific inhibitors, we found that the PERK/ATF4 pathway acted as an upstream signal regulating GSDME-dependent pyroptosis. Overall, our findings show that GSDME-dependent pyroptosis plays a crucial role in the lung injury induced by gestational PFOS exposure, and the PERK/ATF4 pathway may function as a possible mediator of this process.

Effective treatment of a child with adenoidal hypertrophy and severe asthma by omalizumab: a case report.

BACKGROUND: Childhood adenoid hypertrophy (AH) is common and is often associated with allergic asthma, resulting in complications like obstructive sleep apnea syndrome (OSAS). Management of the disease and its complications is often challenging. CASE PRESENTATION: We report here a case of a 10-year-old boy who suffered from severe allergic asthma and rhinitis and was treated with omalizumab. Before the treatment, the childhood asthma control test (C-ACT, 14), visal analog scale (VAS, 7) and lung function (mild obstructive ventilation dysfunction and moderate to severe dysfunction in ventilation in small airway) were seriously affected. Polysomnography showed OSAS (apnea hypopnea index, AHI, 6.4), low hypooxia saturation (lowest pulse oxygen saturation, LoSpO2, 70%), and adenoid hypertrophy (at grade III). After treating with omalizumab for 4 weeks (once treatment), the ventilation function, symptoms of asthma and allergic rhinitis (C-ACT, 24; VAS, 2), and OSAS (AHI: 1.8 and LoSpO2: 92.6%) were all improved, and the adenoids size was also significantly reduced to grade II. And during the following 3 times of treatment, the allergic symptoms continued improving, and the size of adenoid was reduced to grade I. Even 6.5 months after cessation of omalizumab, the size of adenoid remained at grade I. CONCLUSION: This is the first documented case that childhood adenoid hypertrophy can be significantly improved by omalizumab.

An Infant With Interstitial Lung Disease of Rare Cause.

CASE PRESENTATION: An 11-month-old boy was admitted to our hospital because of "recurrent cough with intermittent dyspnea for more than 8 months, aggravated for 1 month." The baby began experiencing a recurrent milk-choking problem within 1.5 months after birth. He had been hospitalized four times, but the symptoms recurred. One month previously, the symptoms were aggravated and a chest CT scan performed at outside hospital showed interstitial changes. Pediatric bronchoscopy revealed bronchial inflammatory features, with hemosiderin-laden macrophages being found in BAL fluid (BALF). Also, periodic acid-Schiff (PAS) staining showed positive results, which indicated the possibility of pulmonary alveolar proteinosis (PAP) or idiopathic pulmonary hemosiderosis (IPH).