Identification of autophagy related genes in predicting the prognosis and aiding 5- fluorouracil therapy of colorectal cancer.

The emergence of 5-Fluorouracil (5-FU) resistance is the barrier to effective clinical outcomes for colorectal cancer (CRC) patients. Autophagy was found to be involved in protecting tumor cells from 5-FU. However, the specific role of autophagy-related genes in CRC 5-FU resistance remains unclear. In this study, HSPB8 among 34 differentially expressed ARGs in CRC was identified to be the hub ARGs in 5-FU resistant which was down-regulated in CRC samples when compared with normal samples but up-regulated in CRC samples with relatively higher lymphatic invasion, later stages and poor prognosis of CRC. Mechanistic analysis demonstrated that due to the recruitment of CAFs, HSPB8 expression was enhanced in CRC cells so that HSPB8 could act together with its co-chaperone BAG3 in autophagy drived 5-FU resistance. Furthermore, the augmented expression level of HSPB8 was found to be significantly correlated to the immune cell infiltration such as Treg cells, macrophages, monocyte and dendritic cells and so on. Our results suggested CAFs driving HSPB8 induced CRC 5-FU resistance by promoting tumor autophagy would provide a new strategy in seeking potential CRC therapeutic target.

Metabonomics Approach to Assessing the Modulatory Effects of Kisspeptin-10 on Liver Injury Induced by Heat Stress in Rats.

The protective effects of Kisspeptin on heat-induced oxidative stress in rats were investigated by using a combination of biochemical parameters and metabonomics. Metabonomic analyses were performed using gas chromatography/mass spectrometry in conjunction with multivariate and univariate statistical analyses. At the end point of the heat stress experiment, histological observation, ultrastructural analysis and biochemical parameters were measured. Metabonomic analysis of liver tissue revealed that Kisspeptin mainly attenuated the alteration of purine metabolism and fatty acid metabolism pathways. Futhermore, Kisspeptin also increased the levels of GSH, T-AOC as well as SOD activities, and upregulated MDA levels. These results provide important mechanistic insights into the protective effects of Kisspeptin against heat-induced oxidative stress.

[Myeloperoxidase in the plasma of patients with acute coronary syndrome].

OBJECTIVE: To determine the diagnostic value and efficacy for risk stratification of myeloperoxidase (MPO) levels in patients with acute coronary syndrome (ACS). METHODS: One hundred and sixty-two patients were enrolled in this study. All patients underwent coronary angiography. They were divided into 3 groups: ACS group (n=54), SAP group (n=54) and control group (n=54). Blood samples were taken from the artery before angiography in all patients and the concentrations of MPO, hsCRP and cTnI were measured. Each subject was asked details of history of hypertension, hyperlipidemia, diabetes and smoking habits. The efficacy of therapy, the cardiovascular events (myocardial infarction, the need for revascularization, or death) were recorded after 6 months of follow-up. RESULTS: The plasma MPO level in ACS group (30.98 ng/mL) was significantly higher than those in the SAP group (14.67 ng/mL) and the control group(14.23 ng/mL)(P<0.01), and the plasma MPO levels in patients of the SAP group and the control group were not significantly different (P=0.74). There was no obvious correlation between the levels of plasma MPO and the serum levels of cTnI, hsCRP,the prevalence of the 4 major risk factors for CHD. Multivariate logistic regression analysis showed that plasma MPO level, free plasma glucose and sex were the significant variables. The risk for subsequent cardiovascular events was higher in the patients with elevated level of MPO. CONCLUSION: Plasma MPO may be a new risk biomarker for ACS and may predict the incidence of subsequent cardiovascular events.