2.Clinicopathological Characteristics and Therapeutic Effect of Patients with Non-small Cell Lung Cancer and Uncommon EGFR Mutations
Wenjia SUN ; Junqiu YUE ; Manxiang WANG
Cancer Research on Prevention and Treatment 2023;50(12):1221-1226
Objective To investigate the clinicopathological characteristics and treatment effect of patients with non-small cell lung cancer (NSCLC) and uncommon epidermal growth factor receptor (
3.A novel and low-toxic peptide DR3penA alleviates pulmonary fibrosis by regulating the MAPK/miR-23b-5p/AQP5 signaling axis.
Dan WANG ; Bochuan DENG ; Lu CHENG ; Jieru LI ; Jiao ZHANG ; Xiang ZHANG ; Xiaomin GUO ; Tiantian YAN ; Xin YUE ; Yingying AN ; Bangzhi ZHANG ; Wenle YANG ; Junqiu XIE ; Rui WANG
Acta Pharmaceutica Sinica B 2023;13(2):722-738
Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH2) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH2) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.