A comprehensive analysis of the microbiota composition and host driver gene mutations in colorectal cancer.

Studies of both, microbiota and target therapy associated with gene mutations in colorectal cancer, (CRC) have attracted increasing attention. However, only a few of them analyzed the combined effects on CRC. we analyzed differences in intestinal microbiota of 44 colorectal cancer patients and 20 healthy controls (HC) using 16S rRNA gene sequencing of fecal samples. For 39 of the CRC patients, targeted Next Generation Sequencing (NGS) was carried out at formalin fixed paraffin embedded (FFPE) samples to identify somatic mutation profiles. Compared to the HC group, the microbial diversity of CRC patients was significantly lower. In the CRC group, we found a microbiome that was significantly enriched for strains of Bifidobacterium, Bacteroides, and Megasphaera whereas in the HC group the abundance of Collinsella, Faecalibacterium, and Agathobacter strains was higher. Among the mutations detected in the CRC group, the APC gene had the highest mutation rate (77%, 30/39). We found that the KRAS mutant type was closely associated with Faecalibacterium, Roseburia, Megamonas, Lachnoclostridium, and Harryflintia. Notably, Spearman correlation analysis showed that KRAS mutations were negatively correlated with the existence of Bifidobacterium and positively correlated with Faecalibacterium. By employing 16S rRNA gene sequencing, we identified more unique features of microbiota profiles in CRC patients. For the first time, our study showed that gene mutations could directly be linked to the microbiota composition of CRC patients. We hypothesize that the effect of a targeted colorectal cancer therapy is also closely related to the colorectal flora, however, this requires further investigation.

Knockdown of LINC01224 Suppresses Colon Cancer Progression by Sponging miR-485-5p to Downregulate MCL1.

BACKGROUND: Colon cancer (CC) is the most commonly occurring malignant tumor in the world. The current cancer treatment options have been less effective especially in the advanced stages of CC and patients have poor overall survival. Hence, there is an urgent need to explore novel molecular therapeutic targets for CC treatment. METHODS: qRT-PCR was performed to detect the levels of lncRNA LINC01224 (LINC01224), microRNA-485-5p (miR-485-5p), MCL1 in CC tumor tissues or cell lines. Two si-RNAs against LINC01224 were used to silence the level of LINC01224, and CCK-8 assay, colony formation assay, and transwell assay were performed to explore the role of LINC01224 on the proliferation, migration, and invasion of CC cell lines. Kaplan-Meier method was applied for evaluating the association between LINC01224 level and the overall survival of CC patients. Through bioinformatics analysis, we found that LINC01224 sponged miR-485-5p and consequently targeted MCL1. Dual-luciferase reporter assay, RNA pull-down assay, qRT-PCR, and Western blot assay were conducted for verification of the interactions among LINC01224, miR-485-5p, and MCL1. Furthermore, the role of LINC01224/miR-485-5p/MCL1 axis in CC progression was investigated by CCK-8 assay, colony formation assay, and transwell assay. RESULTS: LINC01224 was highly expressed in CC tumor tissues and CC cell lines, and its expression was associated with the overall survival of CC patients. The LINC01224-siRNAs (si-LINC01224) markedly suppressed the level of LINC01224 in CC cell lines (HT29 and SW480 cells) and consequently significantly suppressed the proliferation, migration, and invasion of the HT29 and SW480 cells. LINC01224 was verified to sponge miR-485-5p and consequently targeted MCL1. MiR-485-5p inhibitor or MCL1 overexpression (MCL1 OE) markedly restored the repressive effect of the si-LINC01224 pool on MCL1 expression level, as well as proliferation, migration, and invasion of HT29 and SW480 cells. CONCLUSION: This study identified LINC01224/miR-485-5p/MCL1 axis as a novel molecular therapeutic target involved in CC progression.

The effects of calcination temperature of support on Au/CuO-ZrO2 catalysts for oxidation of glycerol to dihydroxyacetone.

Dihydroxyacetone (DHA) is a fine chemical and has been widely used in the cosmetics industry. In this work, DHA was synthesized with high selectivity over Au catalysts, also supported by Cu-Zr mixed oxide calcined at different temperatures. The effects of the calcination temperature of supports on the properties and catalytic performance for glycerol oxidation to dihydroxyacetone were also studied. BET and CO2-TPD measurements demonstrated that the increase in the support calcination temperature reduced the specific surface area of the catalyst and further reduced the surface basic sites of the catalysts. With increased support calcination temperature, the surface content of Au0 and the dispersion of Au first increase until the calcination temperature of the support was 600 °C and then decrease. It was also observed that the glycerol conversion is positively correlated with the surface content of Au0 and the dispersion of Au, while upon the increase of the amount of the basic sites, the catalytic activity increases first and then decreases. The suitable support calcination temperature is beneficial for the conversion of glycerol, and the best catalytic performance is obtained when the calcination temperature is 600 °C.

Selective Oxidation of Glycerol to Dihydroxyacetone over Au/CuxZr1-xOy Catalysts in Base-Free Conditions.

In this paper, a series of Cu-Zr mixed metal oxide-supported Au catalysts were prepared by deposition-precipitation and evaluated for selective oxidation of glycerol to dihydroxyacetone (DHA) in base-free conditions. The best catalytic performance was obtained with DHA selectivity of up to 95% and yield of 70% in 4 h, 50 °C and PO2 = 0.2 MPa over the Au/Cu0.95Zr0.05 and Au/Cu0.9Zr0.1 catalysts. Combined with the characterization results of Brunauer-Emmett-Teller, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and CO2 temperature programmed desorption, it was proposed that the content of Au0, the size of Au, and the basicity of the catalyst affected the glycerol conversion and DHA selectivity. After the catalyst was recycled four times, the glycerol conversion decreased by about 14% which might result from the carbon deposition or the byproduct adsorption and the agglomeration of Au particle.

Solvent-Free Production of Isosorbide from Sorbitol Catalyzed by a Polymeric Solid Acid.

A series of polymeric solid acid catalysts (PDSF-x) is prepared by grafting strong electron-withdrawing groups (-SO2 CF3 ) on a sulfonic acid-modified polydivinylbenzene (PDS) precursor synthesized hydrothermally. The effect of acid strength on sorbitol dehydration is investigated. The textural properties, acidity, and hydrophobicity are characterized by using Brunauer-Emmett-Teller analysis, elemental analysis, and contact angle tests. The results of FTIR spectroscopy and X-ray photoelectron spectroscopy show that both -SO3 H and -SO2 CF3 are grafted onto the polymer network. We used solid-state 31 P NMR spectroscopy to show that the acid strength of PDSF-x is enhanced significantly compared with that of PDS, especially for PDSF-0.05. As a result, PDSF-0.05 exhibits the highest isosorbide yield up to 80 %, a good turnover frequency of 231.5 h-1 (compared to other catalysts), and excellent cyclic stability, which is attributed to its large specific surface area, appropriate acid strength, hydrophobicity, and stable framework structure. In addition, a plausible reaction pathway and kinetic analysis are proposed.

Dynamic impact of inflammation-based indices in colorectal cancer patients receiving FOLFOX-based chemotherapy.

Background: Inflammatory cellular response is implicated in the pathogenesis of colorectal cancer (CRC). Nevertheless, the dynamic effects of inflammatory index coNLR (neutrophil-to-lymphocyte ratio)-PLR (platelet-to-lymphocyte ratio) during chemotherapy remain elusive. Methods: The baseline clinical data and laboratory parameters of 480 CRC patients who received palliative resection of primary tumors and FOLFOX-based chemotherapy from January 2007 to January 2013 were retrospectively analyzed. Receiver operating characteristic curves were plotted to obtain the predictive NLR and PLR values, and to calculate the coNLR-PLR score. The Kaplan-Meier method was used to estimate the rates of recurrence-free survival (RFS) and overall survival (OS), and the Cox proportional hazards model was employed for analysis. Results: The dynamic cut-off values of NLR during four periods of chemotherapy were 3.029, 2.466, 2.102 and 1.795, respectively, and those of PLR were 216.438, 187.572, 169.027 and 174.368, respectively. A higher coNLR-PLR was significantly associated with lower rates of RFS and OS (P<0.05). Both univariate and multivariate analyses showed that coNLR-PLR was a significant independent prognostic factor for RFS and OS (P<0.05). Conclusions: CoNLR-PLR was a significant prognostic predictor for CRC patients who received FOLFOX-based chemotherapy. Evaluating this index can accurately predict the clinical treatment outcomes after chemotherapy.