C/EBP homologous protein (Chop) has been shown to have altered expression in patients with idiopathic pulmonary fibrosis (IPF), but its exact role in IPF pathoaetiology has not been fully addressed. Studies conducted in patients with IPF and Chop(-/-) mice have dissected the role of Chop and endoplasmic reticulum (ER) stress in pulmonary fibrosis pathogenesis. The effect of Chop deficiency on macrophage polarization and related signalling pathways were investigated to identify the underlying mechanisms. Patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis were affected by the altered Chop expression and ER stress. In particular, Chop deficiency protected mice against BLM-induced lung injury and fibrosis. Loss of Chop significantly attenuated transforming growth factor β (TGF-β) production and reduced M2 macrophage infiltration in the lung following BLM induction. Mechanistic studies showed that Chop deficiency repressed the M2 program in macrophages, which then attenuated TGF-β secretion. Specifically, loss of Chop promoted the expression of suppressors of cytokine signaling 1 and suppressors of cytokine signaling 3, and through which Chop deficiency repressed signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma signaling, the essential pathway for the M2 program in macrophages. Together, our data support the idea that Chop and ER stress are implicated in IPF pathoaetiology, involving at least the induction and differentiation of M2 macrophages.

Adenylate kinase 2 (AK2) is a wide-spread and highly conserved protein kinase whose main function is to catalyze the exchange of nucleotide phosphate groups. In this study, we showed that AK2 regulated tumor cell metastasis in lung adenocarcinoma. Positive expression of AK2 is related to lung adenocarcinoma progression and poor survival of patients. Knockdown or knockout of AK2 inhibited, while overexpression of AK2 promoted, human lung adenocarcinoma cell migration and invasion ability. Differential proteomics results showed that AK2 might be closely related to epithelial-mesenchymal transition (EMT). Further research indicated that AK2 regulated EMT occurrence through the Smad-dependent classical signaling pathways as measured by western blot and qPCR assays. Additionally, in vivo experiments showed that AK2-knockout in human lung tumor cells reduced their EMT-like features and formed fewer metastatic nodules both in liver and in lung tissues. In conclusion, we uncover a cancer metastasis-promoting role for AK2 and provide a rationale for targeting AK2 as a potential therapeutic approach for lung cancer.

The aim of the present study was to formulate the novel pediatric suspension containing nanoparticulate Zafirlukast (ZFR) for the treatment of pediatric asthma. The ZFR loaded nanoparticles (NPs) were formulated by ionotropic external gelation method using tripolyphosphate (TPP) and Tween 80. NPs were characterized for drug loading, encapsulation efficiency, surface morphology, saturation solubility, particle size, zeta potential and polydispersity index (PDI). The optimized NP formulation was used for the development of suspension. The suspensions were characterized for pH, viscosity, sedimentation volume, dissolution and drug content. The encapsulation efficiency of NPs was found between 93.24% and 98.57% with drug loading in the range of 26.50-35.90%. All formulations were found of nanosized in nature (150-220 nm) with zeta potential (19.18-21.41 mV). PDI of all NP formulations was found less than 0.3. The NPs were spherical and smooth in nature. The saturation solubility of ZFR was enhanced nearly 16 times as compared to pure ZFR. The optimized suspension showed almost 100% ZFR release within the period of 30 min. The reduction in lung resistance (RI) was found nearly four fold as compared to the control group animals. The study supported the efficacy of suspension containing nanoparticulate ZFR in asthmatic animals.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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