Lung diseases remain a serious problem for public health. The immune status of the body is considered to be the main influencing factor for the progression of lung diseases. HMGB1 (high‐mobility group box 1) emerges as an important molecule of the body immune network. Accumulating data have demonstrated that HMGB1 is crucially implicated in lung diseases and acts as independent biomarker and therapeutic target for related lung diseases. This review provides an overview of updated understanding of HMGB1 structure, release styles, receptors and function. Furthermore, we discuss the potential role of HMGB1 in a variety of lung diseases. Further exploration of molecular mechanisms underlying the function of HMGB1 in lung diseases will provide novel preventive and therapeutic strategies for lung diseases.

Type III phosphatidylinositol-4-kinase beta (PI4KIII␤) was previously implicated in hepatitis C virus (HCV) replication by small interfering RNA (siRNA) depletion and was therefore proposed as a novel cellular target for the treatment of hepatitis C. Medicinal chemistry efforts identified highly selective PI4KIII␤ inhibitors that potently inhibited the replication of genotype 1a and 1b HCV replicons and genotype 2a virus in vitro. Replicon cells required more than 5 weeks to reach low levels of 3-to 5-fold resistance, suggesting a high resistance barrier to these cellular targets. Extensive in vitro profiling of the compounds revealed a role of PI4KIII␤ in lymphocyte proliferation. Previously proposed functions of PI4KIII␤ in insulin secretion and the regulation of several ion channels were not perturbed with these inhibitors. Moreover, PI4KIII␤ inhibitors were not generally cytotoxic as demonstrated across hundreds of cell lines and primary cells. However, an unexpected antiproliferative effect in lymphocytes precluded their further development for the treatment of hepatitis C. C hronic hepatitis C virus (HCV) infection, a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma, afflicts approximately 3% of the world's population (24). The current standard of care for treating hepatitis C is pegylated interferon and ribavirin, which shows poor tolerability and is capable of achieving a sustained viral response in only half of genotype 1 patients (7). Two NS3 protease inhibitors, telaprevir and boceprevir, have been approved recently, and additional direct-acting antivirals are in clinical development. While triple therapy with interferon, ribavirin, and a protease inhibitor increases the percentage of patients showing a sustained viral response to 75% and can shorten the treatment time, it still has limitations: only genotype 1 patients are responsive, side effects (such as anemia) prevent the use in transplant patients, and the inconvenient dosing schedule (three times a day) might cause noncompliance. Development of viruses resistant to direct antivirals occurs very rapidly and leads to relapse and viral breakthrough. A possible exception might be nucleoside inhibitors, since viruses with resistance mutations are not viable. We therefore executed high-throughput small interfering RNA (siRNA) screens in order to identify novel cellular targets for the treatment of HCV. Type III phosphatidylinositol-4-kinases (PI4KIIIs) were identified from these studies and in screens performed in other laboratories (3,4,(20)(21)(22).Mammalian cells express a large number of lipid kinases, including four enzymes that phosphorylate phosphatidylinositol at position four of the inositol ring, the phosphatidylinositol-4-kinases (PI4Ks). Lipid kinases are involved in multiple functions of the cell, of which phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) signaling is the most thoroughly investigated process. The four PI4Ks (type II ␣ and ␤ and type III ␣ and ␤) are localized to different sites in the cell by pro...

BackgroundMalignant glioma is a common primary tumor of the central nervous system. Brevican, an abundant extracellular matrix component in the adult brain, plays a critical role in the process of glioma. The mechanisms for the highly invasive behavior of gliomas are still poorly understood. The aim of this study was to examine whether brevican is a predictor of glioma and its roles in glioma cell motility.MethodsIn this study, immunohistochemistry staining for brevican expression was performed in malignant gliomas and benign controls. We also explored the effects of brevican on cell adhesion and migration in brevican-overexpressed cells. Knockdown of brevican expression was achieved by stable transfection of U251 cells transduced with a construct encoding a short hairpin DNA directed against the brevican gene, which correspondingly, down-regulated the proliferation, invasion and spread of brevican-expressing cells. Moreover, the role of brevican in the growth and progression of glioma was demonstrated by in vivo studies.ResultsOur results provide evidence for the molecular and cellular mechanisms that may underlie the motility-promoting role of brevican in the progression of glioma. The role of brevican as a target for immunotherapy might be taken into consideration in future studies.ConclusionsThis study suggests that expression of brevican is associated with glioma cell adhesion, motility and tumor growth, and also is related to glioma cell differentiation, therefore it may be a marker for malignance degree of glioma

Background The new coronavirus (COVID-19) rapidly resulted in a pandemic. We report the characteristics of patients with severe or critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan city, China, and the risk factors related to infection severity and death. Methods We extracted the demographic and clinical data of 7283 patients with severe COVID-19 infection from designated Wuhan hospitals as of 25 February 2020. Factors associated with COVID-19 critical illness and mortality were analysed using logistic- and Cox-regression analyses. Results We studied 6269 patients with severe COVID-19 illness and 1014 critically ill patients. The median (IQR) age was 64 (53–71) years; 51.2% were male, 38.9% were retirees and 7.4% had self-reported histories of chronic disease. Up to the end of the study, 1180 patients (16.2%) recovered and were discharged, 649 (8.9%) died and the remainder were still receiving treatment. The number of daily confirmed critical cases peaked between 23 January and 1 February 2020. Patients with advanced age [odds ratio (OR), 1.03; 95% confidence intervals (CIs), 1.03–1.04], male sex (OR, 1.57; 95% CI, 1.33–1.86) and pre-existing diabetes (OR, 2.11), hypertension (OR, 2.72), cardiovascular disease (OR, 2.15) or respiratory disease (OR, 3.50) were more likely to be critically ill. Compared with those who recovered and were discharged, patients who died were older [hazard ratio (HR), 1.04; 95% CI, 1.03–1.05], more likely to be male (HR, 1.74; 95% CI, 1.44–2.11) and more likely to have hypertension (HR, 5.58), cardiovascular disease (HR, 1.83) or diabetes (HR, 1.67). Conclusion Advanced age, male sex and a history of chronic disease were associated with COVID-19 critical illness and death. Identifying these risk factors could help in the clinical monitoring of susceptible populations.