1 H NMR-based metabonomic evaluation of the pesticides camptothecin and matrine against larvae of Spodoptera litura.

BACKGROUND: Camptothecin (CPT) and matrine (MAT) have potential as botanical pesticides against several pest species. However, the mechanisms of metabolic and physiological changes in pests induced by CPT and MAT are unknown. In this study, a toxicological test, an NMR-based metabolomic study, an enzymatic test, and an RT quantitative PCR (RT-qPCR) experiment were all conducted to examine the effect of CPT and MAT on Spodoptera litura. RESULTS: CPT (0.5-1%) exerted high toxicity against larvae of S. litura and caused growth stagnation and high mortality of larvae. A variety of metabolites were significantly influenced by 0.5% CPT, including several energy-related metabolites such as trehalose, lactate, succinate, citrate, malate, and fumarate. In contrast, MAT showed low toxicity against larvae and induced almost no changes in hemolymph metabolites of S. litura. Enzymatic tests showed that trehalase activity was significantly decreased in larvae after feeding with 0.5% CPT. RT-qPCR showed that the transcription levels of alanine aminotransferase, malate dehydrogenase, and isocitrate dehydrogenase were decreased while lactate dehydrogenase was increased in the 0.5% CPT-treated group. CONCLUSIONS: These data indicate that one of the important mechanisms of CPT against S. litura larvae is via the inhibition of trehalose hydrolysis and glycolysis. Our findings also suggest that CPT exhibits a stronger toxicological effect than MAT against S. litura, which provides basic information for the application of CPT in the control of S. litura or other lepidoptera pests.

FGL2 regulates IKK/NF-κB signaling in intestinal epithelial cells and lamina propria dendritic cells to attenuate dextran sulfate sodium-induced colitis.

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by an abnormal immune response. Fibrinogen-like protein 2 (FGL2) is known to have immunoregulatory and anti-inflammatory activity. The level of FGL2 is elevated in patients with IBD; however, its comprehensive function in IBD is almost unknown. In our study, we explored the effect of FGL2 on dextran sulfate sodium (DSS)-induced colitis in mice and on NF-κB signaling in intestinal epithelial cells (IECs) and lamina propria dendritic cells (LPDCs). We founded that FGL2-/- mice in the colitis model showed more severe colitis manifestations than WT mice did, including weight loss, disease activity index (DAI), and colon histological scores. FGL2-/- mice treated with DSS produced more proinflammatory cytokines (IL-1ß, IL-6, TNF-α) in serum than WT mice did and demonstrated upregulated expression of TNF-α and inflammatory marker enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) in the colon tissue. Our data suggested that DSS-treated FGL2-/- mice showed stronger activation of NF-κB signaling, especially in IECs. Next, we demonstrated that recombinant FGL2 (rFGL2) inhibited the production of proinflammatory cytokines and the expression of inflammatory marker enzymes by downregulating the NF-κB signaling in HT-29 cells. Finally, we discovered that LPDCs from the colon of DSS-treated FGL2-/- mice showed significantly upregulated expression of surface maturation co-stimulatory molecules, including CD80, CD86, CD40, and MHC class II molecules compared with that in WT mice. In addition, LPDCs in FGL2-/- treated with DSS exhibited excessive NF-κB activity and the administration of rFGL2 to FGL2-/- mice could rescue the aggravated results of FGL2-/- mice. Taken together, our findings demonstrated that FGL2 might be a target for further therapy of IBD.

Prognostic value of serum lactate kinetics in critically ill patients with cirrhosis and acute-on-chronic liver failure: a multicenter study.

Lactate clearance (Δ24Lac) was reported to be inversely associated with mortality in critically ill patients. The aim of our study was to assess the value of Δ24Lac for the prognosis of critically ill patients with cirrhosis and acute-on-chronic liver failure (ACLF). We analysed 954 cirrhotic patients with hyperlactatemia admitted to intensive care units (ICUs) in the United States and eastern China. The patients were followed up for at least 1 year. In the unadjusted model, we observed a 15% decrease in hospital mortality with each 10% increase in Δ24Lac. In the fully adjusted model, the relationship between the risk of death and Δ24Lac remained statistically significant (hospital mortality: odds ratio [OR] 0.84, 95% confidence interval [CI]: 0.78- 0.90, p < 0.001; 90-day mortality: hazard ratio [HR] 0.94, 95%CI 0.92- 0.97, p < 0.001; for Δ24Lac per 10% increase). Similar results were found in patients with ACLF. We developed a Δ24Lac-adjusted score (LiFe-Δ24Lac), which performed significantly better in the area under the receiver operating characteristic curves (AUROCs) than the original LiFe score for predicting mortality. Lactate clearance is an independent predictor of death, and the LiFe-Δ24Lac score is a practical tool for stratifying the risk of death.

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis.

BACKGROUND: Many factors are reported to be related to the prognosis of patients with esophageal adenocarcinoma (EAC), but few reliable and straightforward tools for clinicians to estimate individual mortalities have been developed. This study aimed to evaluate the probability of cancer-specific death for patients with EAC and to build nomograms for predicting long-term cancer-specific mortality and overall mortality for EAC patients. METHODS: Between 2004 and 2013, a total of 20,623 patients were identified from the surveillance, epidemiology, and end results (SEER) database and randomly divided into training (N=14,436) and validation (N=6,187) cohorts. The cumulative incidence functions (CIFs) of EAC-specific death and other causes were evaluated at the 1st, 3rd, and 5th year after diagnosis. We integrated the significant prognostic factors to construct nomograms and subjected them to internal and external validation. RESULTS: The CIFs of EAC-specific survival at 1, 3, and 5 years after diagnosis were 60.9%, 37.1%, and 31.3%, respectively. Predictors for cancer-specific mortality for EAC comprised tumor grade, tumor extension, the involvement of lymph nodes, distant metastasis, surgery of primary site, insurance recode, and marital status. For overall mortality, it also included the predictor of age at diagnosis. The nomograms were well-calibrated and had good discriminative ability with concordance indexes (c-indexes) of 0.733, 0.728, and 0.728 for 1-, 3- and 5-year prognosis prediction of EAC-specific mortality respectively, and 0.726, 0.720, 0.719 for 1-, 3-, and 5-year prognosis prediction of overall mortality respectively. CONCLUSIONS: We proposed and validated the effective and convenient nomograms to predict cancer-specific mortality and the overall mortality for patients with EAC, which only require the basic information available in clinical practice.