Despite the critical role of microRNA in inflammatory response, little is known about its function in inflammation-induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS). To investigate the potential role of microRNA146a (miR-146a) in ALI, we used lipopolysaccharide (LPS)-induced ALI rat model. Our data revealed that LPS-induced lung injury in rats resulted in significant upregulation of proinflammatory cytokine tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, and miR-146a expression. LPS treatment also leads to higher expression of miR-146a as well as increase in secretion of TNF-α, IL-6, and IL-1β in alveolar macrophage (AM) NR8383 cells in a time-dependent manner. Manipulation with miR146a mimic significantly suppressed LPS-mediated TNF-α, IL-6, and IL-1β induction in NR8383 cells by repressing expression of IRAK-1 and TRAF-6. These data clearly indicate that the upregulation of miR146a suppresses inflammatory mediators in LPS induced-ALI model. Therefore, miR-146a may be therapeutically targeted as a mean to repress inflammatory response following ALI.

We propose that miR-132 functions as a negative regulator of the inflammatory response in alveolar macrophages by potentiating the cholinergic anti-inflammatory pathway, and represents a potential therapeutic leverage point in modulating inflammatory responses.

The current study observed a higher level of miR-155 in the BALF from sepsis patients with acute respiratory distress syndrome and demonstrated that miR-155 alleviated inflammation in septic lung injury in mouse and cell models by inducing autophagy via inhibition of TAB2.

Lung cancer is the leading cause of cancer mortality worldwide. Approximately 85% of all lung cancer cases are classified as non-small cell lung cancer (NSCLC). Currently, there is no standard method to predict the survival of patients with NSCLC. Insulin-like growth factor-binding proteins (IGFBPs) function as modulators of IGF signaling and are attracting increasing attention for their role in NSCLC. However, the prognostic values of individual IGFBPs in NSCLC, particularly at the mRNA level, remain unknown. In the present study, the distinct expression patterns and prognostic values of IGFBP family members in patients with NSCLC through bioinformatics analysis were reported using a series of databases, including Gene Expression Profiling Interactive Analysis, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, and the Database for Annotation, Visualization and Integrated Discovery. In patients with NSCLC, IGFBP2 and IGFBP3 were significantly upregulated, while IGFBP6 was downregulated. High IGFBP1/2/4 expression was correlated with poor overall survival (OS) in all NSCLC types, especially adenocarcinoma; however, high IGFBP2/5 expression was significantly correlated with favorable OS only in patients with squamous cell carcinoma. In addition, aberrant IGFBP1/2/3/4/5 mRNA levels were associated with the prognosis of subsets of NSCLC with different clinicopathological features. These results indicated that various IGFBPs can serve as useful prognostic biomarkers and as potential targets for NSCLC therapies.

No abstract

To investigate the association between circulating omentin-1 levels and polycystic ovary syndrome (PCOS) in women, a meta-analysis was performed. A systematic literature search using PubMed, Embase and Web of Science was carried out. Ten articles with 13 studies were included in this meta-analysis, which included a total of 1264 subjects (733 patients with PCOS and 531 controls). The pooled standard mean difference (SMD) and 95% confidence interval (CI) were used to estimate the association between omentin-1 levels and PCOS. Circulating omentin-1 levels were lower in PCOS with an SMD (95% CI) of -0.67 (-0.91, -0.43) and p = 0.000 (random-effects). However, significant heterogeneity was detected across studies (I=73.6% and p = 0.000). The subgroup analysis suggested that omentin-1 levels in PCOS patients were associated with HOMA-IR ratio. Meta-regression analysis indicated region was the main source of heterogeneity (p = 0.048). The results of this meta-analysis suggested that circulating omentin-1 levels are significantly lower in women with PCOS compared with controls, which indicated that omentin-1 may play a role in the pathologic processes of PCOS.

Epithelial–mesenchymal transition (EMT) has been shown to be linked to a poor prognosis, particularly in patients with non-small-cell lung cancer. Nevertheless, little is known regarding the existence of EMT-related gene signatures and their prognostic values in lung adenocarcinoma (LUAD). In the current study, we systematically profiled the mRNA expression data of patients with LUAD in The Cancer Genome Atlas and Gene Expression Omnibus databases using a total of 1,184 EMT-related genes. The prognostic values of the EMT-related genes used to develop risk score models for overall survival were determined using LASSO and Cox regression analyses. A prognostic signature that consisted of nine unique EMT-related genes was generated using a training set. A nomogram, incorporating this EMT-related gene signature and clinical features of patients with LUAD, was constructed for potential clinical use. Calibration plots, decision-making curves, and receiver operating characteristic curve analysis showed that this model had a good ability to predict the survival of patients with LUAD. The EMT-associated gene signature and prognostic nomogram established in this study were reliable in predicting the survival of patients with LUAD. Thus, we first identified a novel EMT-related gene signature and developed a nomogram for predicting the prognosis of patients with LUAD.

Background/aims Isoalantolactone (IATL) is one of multiple isomeric sesquiterpene lactones and is isolated from inula helenium. IATL has multiple functions such as antibacterial, antihelminthic and antiproliferative activities. IATL also inhibits pancreatic cancer proliferation and induces apoptosis by increasing ROS production. However, the detailed mechanism of IATL-mediated pancreatic cancer apoptosis remains largely unknown. Methods In current study, pancreatic carcinoma cell lines (PANC-1, AsPC-1, BxPC-3) and a mouse xenograft model were used to determine the mechanism of IATL-mediated toxic effects. Results IATL (20μM) inhibited pancreatic adenocarcinoma cell lines proliferation in a time-dependent way; while scratch assay showed that IATL significantly inhibited PANC-1 scratch closure (P<0.05); Invasion assays indicated that IATL significantly attenuated pancreatic adenocarcinoma cell lines invasion on matrigel. Signal analysis showed that IATL inhibited pancreatic adenocarcinoma cell proliferation by blocking EGF-PI3K-Skp2-Akt signal axis. Moreover, IATL induced pancreatic adenocarcinoma cell apoptosis by increasing cytosolic Caspase3 and Box expression. This apoptosis was mediated by inhibition of canonical wnt signal pathway. Finally, xenograft studies showed that IATL also significantly inhibited pancreatic adenocarcinoma cell proliferation and induced pancreatic adenocarcinoma cell apoptosis in vivo. Conclusions IATL inhibits pancreatic cancer proliferation and induces apoptosis on cellular and in vivo models. Signal pathway studies reveal that EGF-PI3K-Skp2-Akt signal axis and canonical wnt pathway are involved in IATL-mediated cellular proliferation inhibition and apoptosis. These studies indicate that IATL may provide a future potential therapy for pancreatic cancer.