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Owing to the rapid development and wide clinical application of direct acting antiviral (DAA) drugs in the treatment of hepatitis C virus (HCV) infection, the era of interferon-based therapy has almost come to an end. Cumulative studies show that DAA therapy renders high cure efficiency (>90%) and good safety profile, and may even bring some unexpected benefits to the patients. However, some issues of concern arise, one of which is the resistance mutation of HCV genome leading to failure of treatment. With the aim of providing some meaningful references for the treatment of chronic hepatitis C (CHC), this article summarizes the research progress on benefits of DAA accompanied by viral clearance in the treatment of chronic hepatitis and the drug resistance.

Background Respiratory viral infections (RSV) can induce acute asthma attacks, thereby destroying lung function and accelerating the progression of the disease. However, medications in the stable phase of asthma are often not effective for acute attacks induced by viral infections. We aimed to clarify the possible mechanism of viral infection–induced asthma through fatty acid metabolism. Methods and Results The airway resistances, inflammatory injuries, and oxidative stress in the RSV‐induced animal models were significantly higher than those in the control group at acute phase (7 days) and chronic phase (28 days). Moreover, the concentrations of the medium‐ and long‐chain fatty acids in lung tissue at (28 days) were significantly increased, including 14:0 (myristic acid), 16:0 (palmitic acid, PA), 18:1 (oleic acid, OA), and 18:2 (linoleic acid, LA) using non‐targeted metabonomics. Airway epithelial cells treated with RSV showed the reduced expression of FSP27, RAB8A, and PLIN5, which caused the fusion and growth of lipid droplet (LD), and increased expression of the LD dispersion gene perilipin 2. There was also a decrease in PPARγ expression and an increase in the fatty acid catabolism gene PPARα, causing lipid oxidation, free fatty acid releases, and an upsurge in IL‐1, IL‐2, IL‐4, and IL‐6 expression, which could be abrogated by GPR40 inhibitor. Treated mice or epithelial cells with C18 fatty acid exhibited inhibition of epithelial proliferation, increases of inflammation, and oxidative damage. Conclusions RSV promoted lipid dispersion and utilization, causing enlarged oxidative injuries and an upsurge in the pro‐inflammatory cytokines, leading to the progression of airway hyperresponsiveness (AHR).

ObjectiveSeveral studies have demonstrated the impacts of GTPases of immunity-associated proteins (GIMAPs) on malignant cells. However, the mechanisms through which Gimap5 regulates lung cancer cells are yet to be thoroughly investigated in the literature. Our study aimed to investigate the function of Gimap5 in the development of lung cancer.MethodsThe expression levels of the GIMAP family were analyzed in lung cancer patients of various cancer databases and lung cancer cell lines. After the survival rates of the cells were analyzed, we constructed Gimap5 over-expressed lung cancer cell lines and assessed the effects of Gimap5 on cell migration, cell invasion, cell proliferation and the epithelial-mesenchymal transition (EMT). We later screened the interacting proteins of Gimap5 using Co-IP combined with mass spectrometry and then analyzed the expression and distribution of M6PR, including its impacts on protein-arginine deiminase type-4 (PADI4).ResultsFindings indicated that GIMAP family expression decreased significantly in lung cancer cell lines. We also noticed that the downregulation of the GIMAP family was related to the poor prognosis of lung cancer patients. Our experimental results showed that Gimap5 could inhibit the migration, invasion, proliferation and EMT of lung cancer cell lines. Moreover, we found that Gimap5 promoted the transport of M6PR from the cytoplasm to the cell membrane, thereby inhibiting the enhancement of EMT-related PADI4.ConclusionOur research suggested that Gimap5 could inhibit the growth of lung cancer by interacting with M6PR and that it could be a potential biomarker for the diagnosis and prognosis of lung cancer.

The lung-brain axis is an emerging area of study that got its basis from the gut-brain axis biological pathway. Using Respiratory Synctial Virus (RSV) as the model of respiratory viral pathogen, this study aims to establish some biological pathways. After establishing the mice model, the inflammation in lung and brain were assayed using Hematoxylin-eosin staining, indirect immunofluorescence (IFA), and quantitative reverse-transcription polymerase chain reaction. The biological pathways between lung and brain were detected through metabolomics analysis. In lung, RSV infection promoted epithelial shedding and infiltration of inflammatory cells. Also, RSV immunofluorescence and titerss were significantly increased. Moreover, interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α) were also significantly increased after RSV infection.In brain, the cell structure of hippocampal CA1 area was loose and disordered.Inflammatory cytokines IL-6 and IL-1β expression in the brain also increased, however, TNF-α expression showed no differences among the control and RSV group. We observed an increased expression of microglia biomarker IBA-1 and decreased neuronal biomarker NeuN. In addition, RSV mRNA expression levels were also increased in the brains. 15 metabolites were found upregulated in the RSV group including nerve-injuring metabolite glutaric acid, hydroxyglutaric acid and Spermine. ɑ-Estradiol increased significantly while normorphine decreased significantly at Day 7 of infection among the RSV group. This study established a mouse model for exploring the pathological changes in lungs and brains. There are many biological pathways between lung and brain, including direct translocation of RSV and metabolite pathway.