Bioinformatics analysis and identification of upregulated tumor suppressor genes associated with suppressing colon cancer progression by curcumin treatment

Tumor suppressor genes (TSGs) are commonly downregulated in colon cancer and play a negative role in tumorigenesis and cancer progression by affecting genomic integrity, the cell cycle, and cell proliferation. Curcumin (CUR), a Chinese herb-derived phytochemical, exerts antitumor effects on colon cancer. However, it remains unclear whether CUR exerts its antitumor effects by reactivating TSGs in colon cancer. Here, we demonstrated that CUR inhibited HT29 and HCT116 proliferation and migration by cell-counting kit-8, colony-formation, and wound-healing assays. Furthermore, the comprehensive bioinformatics analysis of mRNA sequencing revealed that 3,505 genes were significantly upregulated in response to CUR in HCT116 cells. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses showed that the most upregulated genes were enriched in cancer pathways containing 37 TSGs. Five (ARHGEF12, APAF1, VHL, CEBPA, and CASP8) of the 37 upregulated TSGs were randomly selected for real-time fluorescence polymerase chain reaction and the verification results showed that these five genes were significantly reactivated after CUR treatment, suggesting that TSGs are related to CUR-mediated colon cancer inhibition. ARHGEF12 is a newly identified TSG and a potential therapeutic target for colon cancer. Furthermore, molecular docking was performed to predict the binding sites of CUR and ARHGEF12, suggesting that CUR can prevent colon cancer cell invasion and metastasis by inhibiting ARHGEF12 and RhoA binding. In conclusion, the present study reveals that CUR inhibits colon cancer cell proliferation and migration by reactivating TSGs, revealing a new mechanism and potential target for colon cancer treatment

Genome-wide investigation and functional characterization of the β-ketoadipate pathway in the nitrogen-fixing and root-associated bacterium Pseudomonas stutzeri A1501

<p>Abstract</p> <p>Background</p> <p>Soil microorganisms are mainly responsible for the complete mineralization of aromatic compounds that usually originate from plant products or environmental pollutants. In many cases, structurally diverse aromatic compounds can be converted to a small number of structurally simpler intermediates, which are metabolized to tricarboxylic acid intermediates via the β-ketoadipate pathway. This strategy provides great metabolic flexibility and contributes to increased adaptation of bacteria to their environment. However, little is known about the evolution and regulation of the β-ketoadipate pathway in root-associated diazotrophs.</p> <p>Results</p> <p>In this report, we performed a genome-wide analysis of the benzoate and 4-hydroxybenzoate catabolic pathways of <it>Pseudomonas stutzeri </it>A1501, with a focus on the functional characterization of the β-ketoadipate pathway. The <it>P. stutzeri </it>A1501 genome contains sets of catabolic genes involved in the peripheral pathways for catabolism of benzoate (<it>ben</it>) and 4-hydroxybenzoate (<it>pob</it>), and in the catechol (<it>cat</it>) and protocatechuate (<it>pca</it>) branches of the β-ketoadipate pathway. A particular feature of the catabolic gene organization in A1501 is the absence of the <it>catR </it>and <it>pcaK </it>genes encoding a LysR family regulator and 4-hydroxybenzoate permease, respectively. Furthermore, the BenR protein functions as a transcriptional activator of the <it>ben </it>operon, while transcription from the <it>catBC </it>promoter can be activated in response to benzoate. Benzoate degradation is subject to carbon catabolite repression induced by glucose and acetate in A1501. The HPLC analysis of intracellular metabolites indicated that low concentrations of 4-hydroxybenzoate significantly enhance the ability of A1501 to degrade benzoate.</p> <p>Conclusions</p> <p>The expression of genes encoding proteins involved in the β-ketoadipate pathway is tightly modulated by both pathway-specific and catabolite repression controls in A1501. This strain provides an ideal model system for further study of the evolution and regulation of aromatic catabolic pathways.</p

Characterization of the Bafilomycin Biosynthetic Gene Cluster from Streptomyces lohii

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96305/1/301_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96305/2/cbic_201200743_sm_miscellaneous_information.pd

Analysis of noninvasive predictive indices of esophageal varices in patients with posthepatitic cirrhosis

ObjectiveTo investigate the clinical significance of noninvasive predictive indices of esophageal varices (EV) in patients with posthepatitic cirrhosis. MethodsSixty-four patients with posthepatitic cirrhosis, who were hospitalized in the Affiliated Hospital of Yan′an University from February 2011 to January 2013, were enrolled in this study. All patients underwent gastroscopy to evaluate EV. The diameter of portal vein (PV), spleen length (SL), spleen thickness (ST), and degree of ascites were determined by abdominal ultrasound, and the spleen index (SI) was calculated. Prothrombin time (PT), serum albumin (Alb), etc., were measured by laboratory testing. Liver function was assessed by Child-Pugh classification. The correlation between each index and EV or severe EV was analyzed based on area under the receiver operating characteristic curve. For normally distributed data, comparison of means between groups was made by one-way analysis of variance; for non-normally distributed data, comparison between groups was made by Kruskal-Wallis H test; correlation analysis was performed by Kendall′s rank correlation test. ResultsAmong the 64 patients, 48 (75%) had various degrees of EV, including 14 mild cases, 12 moderate cases, and 22 severe cases. There were significant differences in SI, Model for End-Stage Liver Disease (MELD) score, MELD-Na score between the patients with EV and those without EV (P＜0.05). PV and SI showed significant differences between the mild cases and severe cases (P＜0.05); SI showed significant differences between the mild cases and moderate cases and between the moderate cases and severe cases (P＜0.05 for both). Alb showed significant difference only between the patients without EV and severe cases (P＜0.01). No significant difference in PT was found between each two patient groups (P＞0.05). As the severity of EV increases, PV, SI, MELD score, and MELD-Na score tended to increase, Alb showed a downward trend, and PT demonstrated no significant changes. The degree of EV was positively correlated with Child-Pugh score (t=0483, P＜0.05), and there was no correlation between the degrees of ascites and EV (P＞005). When SI was higher than 58.96 cm2, its sensitivity, specificity, positive predictive value, and negative predictive value for EV were 91.7%, 100.0%, 100.0%, and 80.1%, respectively. When SI was higher than 70.56 cm2, its sensitivity, specificity, positive predictive value, and negative predictive value for EV were 86.4%, 90.5%, 96.5%, and 68.9%, respectively. ConclusionThere is a certain correlation between degree of EV and Child-Pugh score. PV, Alb, SI, MELD score, and MELD-Na score have predictive values for EV, and SI may be used as a sensitive noninvasive predictive index for EV and severe EV in patients with posthepatitic cirrhosis

CuAlO2/Bi2WO6: a novel p–n type composite with significantly enhanced visible-light photocatalytic reduction of Cr(VI)

The Bi _2 WO _6 and CuAlO _2 powders were synthesized through the method of solid-state reaction. This study prepared the newly and highly effective p–n type CuAlO _2 /Bi _2 WO _6 photocatalysts that had diverse CuAlO _2 compositions by employing an environmentally friendly and economical approach. X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy(SEM), photoluminescence (PL) emission spectra, and UV–vis diffuse reflectance spectroscopy were adopted to characterize the photocatalysts. The as-synthesized CuAlO _2 /Bi _2 WO _6 heterocatalyst was utilized to reduce toxic Cr (VI) ions into Cr (III) by means of photoreduction under visible light irradiation. When CuAlO _2 (1.0 wt.%)/Bi _2 WO _6 was used, the Cr (VI) photoreduction rate constant was 4.7 times as many as that of pure Bi _2 WO _6 . The study also investigated how the ball milling time and CuAlO _2 composition affected the performance of CuAlO _2 /Bi _2 WO _6 . In addition, the stability of composite was investigated. The results revealed that the high conductivity of CuAlO _2 , excellent crystalline quality, and the p–n heterojunction between CuAlO _2 and Bi _2 WO _6 exerted a vital role in enhancing the photoreduction performance. This work explores the design of other new heterocatalysts, especially the p–n type composites containing CuAlO _2