A novel dNTP pyrophosphatase, Mj0226 from Methanococcus jannaschii, which catalyzes the hydrolysis of nucleoside triphosphates to the monophosphate and PPi, has been characterized. Mj0226 protein catalyzes hydrolysis of two major substrates, dITP and XTP, suggesting that the 6-keto group of hypoxanthine and xanthine is critical for interaction with the protein. Under optimal reaction conditions the k(ca)(t) /K(m) value for these substrates was approximately 10 000 times that with dATP. Neither endonuclease nor 3'-exonuclease activities were detected in this protein. Interestingly, dITP was efficiently inserted opposite a dC residue in a DNA template and four dNTPs were also incorporated opposite a hypoxanthine residue in template DNA by DNA polymerase I. Two protein homologs of Mj0226 from Escherichia coli and Archaeoglobus fulgidus were also cloned and purified. These have catalytic activities similar to Mj0226 protein under optimal conditions. The implications of these results have significance in understanding how homologous proteins, including Mj0226, act biologically in many organisms. It seems likely that Mj0226 and its homologs have a major role in preventing mutations caused by incorporation of dITP and XTP formed spontaneously in the nucleotide pool into DNA. This report is the first identification and functional characterization of an enzyme hydrolyzing non-canonical nucleotides, dITP and XTP.

Arylamine N-acetyltransferase (NAT) activities with p-aminobenzoic acid (PABA) and 2-aminofluorene (AF) were determined in H. pylori collected from peptic ulcer patients. Cytosols or suspensions of H. pylori with or without different concentrations of aloe-emodin co-treatment showed different percentages of AF and PABA acetylation. The data indicate that there was decreased NAT activity associated with increased aloe-emodin in H. pylori cytosols. Inhibition of growth study from H. pylori demonstrated that aloe-emodin elicited dose-dependent growth inhibition in H. pylori cultures. The report is the first finding of aloe-emodin inhibition of arylamine NAT activity in a strain of H. pylori.

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Background: Although both chemotherapy and radiotherapy (RT) can sufficiently maintain tumor suppression of colorectal cancer (CRC), these treatments may trigger the expression of nuclear factor kappa B (NF-ĸB) and compromise patients' survival. Regorafenib suppresses NF-ĸB activity in various tumor types. However, whether regorafenib may act as a suitable radiosensitizer to enhance therapeutic efficacy of RT remains unknown. Materials and Methods: Here, we established a CRC-bearing animal model to investigate the therapeutic efficacy of regorafenib in combination with RT, through measurement of tumor growth, body weight, whole-body computed tomography (CT) scan and immunohisto-chemistry staining. Results: Smallest tumor size and weight were found in the combination treatment group. In addition, RT-induced upregulation of NF-ĸB and downstream proteins were diminished by regorafenib. Moreover, the body weight and liver pathology in the treated group were similar to those of the non-treated control group. Conclusion: Regorafenib may enhance the anti-CRC efficacy of RT.Recent innovative radiotherapy (RT) technologies, including intensity-modulated RT, image-guided RT, volumetric-modulated arc therapy, intraoperative RT, and stereotactic body RT (SBRT), are widely used to treat many types of cancer (1-3). RT as neoadjuvant strategy offers therapeutic benefits for patients with colorectal cancer (CRC). The combination of RT and surgical resection or chemotherapy has been shown to reduce the local recurrence rate and improve the survival of patients with CRC (4, 5). For increasing anti-CRC efficacy of RT, novel radiosensitizers that sensitize cancer cells to radiation have been developed (6).

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