Dehydrocostus lactone inhibits BLM-induced pulmonary fibrosis and inflammation in mice via the JNK and p38 MAPK-mediated NF-κB signaling pathways.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible inflammatory disease with a high mortality rate and limited therapeutic options. This study explored the potential role and mechanisms of Dehydrocostus lactone (DHL) in the inflammatory and fibrotic responses in a bleomycin (BLM) induced model. Treatment with DHL significantly reduced pathological injury and fibrosis, the secretion of BLM-induced pro-fibrotic mediators TGF-ß and α-SMA, and components of the extracellular matrix (fibronectin). Additionally, in the early stages of inflammation, DHL administration inhibited the infiltration of inflammatory cells and downregulated the expression of TGF-ß, TNF-α, and IL-6, indicating that DHL treatment effectively alleviated BLM-induced pulmonary fibrosis and inflammation in a dose-dependent manner. Furthermore, BLM induced the production of IL-33 in vivo, which initiated and progressed pulmonary fibrosis by activating macrophages and enhancing the production of IL-13 and TGF-ß. In contrast, a significant decrease in the expression of IL-33 after DHL treatment in vitro showed that DHL strongly reduced IL-13 and TGF-ß. Regarding the mechanism, BLM-induced phosphorylation of JNK, p38 MAPK, and NF-κB were significantly reduced after DHL treatment, which further led to the down-regulation of IL-33 expression, thereby decreasing IL-13 and TGF-ß. Collectively, our data suggested that DHL could exert its anti-fibrosis effect via inhibiting the early inflammatory response by downregulating the JNK/p38 MAPK-mediated NF-κB signaling pathway to suppress macrophage activation. Therefore, DHL has therapeutic potential for pulmonary fibrosis.

A retrospective view of pediatric cases infected with SARS-CoV-2 of a middle-sized city in mainland China.

ABSTRACT: The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 had resulted in a global pandemic. A comprehensive analysis of pediatric COVID-19 cases is essential to decipher the natural features of children under the risk of this disease.In the epidemic period, all the children infected with SARS-CoV-2 in Wuxi, a city with a stable medical system during the COVID-19 outbreak in China, were enrolled for comprehensive data documenting their clinical, prognosis, follow-up, treatment and various tests results. Combing their family cluster characteristics, the epidemiological, hospitalization, and transmission features of children with SARS-CoV-2 were analyzed and discussed.A total of 7 children were enrolled, including 4 mild cases, 1 moderate case, and 2 asymptomatic cases. The common symptoms were fever and dry cough. The length of viral nucleic acid duration in nasopharynx varied and was irrelevant to the severity of the symptom, whether symptomatic or asymptomatic. Two cases showed viral nucleic acid positive recurrence after discharge from the hospital. A child with type 1 diabetes was also focused, for the elevated blood sugar during hospitalization. All these children had close contacts with their family members, some of those were confirmed COVID-19 cases.We provided a holistic and detailed portrayal of the pediatric COVID-19 cases in a typical city of timely response to the epidemic. While the family cluster exhibits the major transmission mode, attention should be paid for the potential risk since the expanded social space of children in future.