Correlation analysis for alterations of intestinal flora in hepatocellular carcinoma patients: combinatorial detection of Coriobacterium, Atopobium, Coprococcus and Veillonella dispar may be a new method for HCC diagnosis.

Introduction. Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world. Due to the characteristics of low early diagnosis rate, high malignancy and rapid progression, the majority of diagnosed patients are in the middle or late stage. Accumulating evidence reveals that intestinal flora imbalance will aggravate HCC by disturbing immune regulation, especially interleukin expression. Therefore, intestinal flora-based methods have the potential to be new diagnostic or therapeutic methods for HCC.Hypothesis. Compositions of intestinal florae were different between HCC patients and healthy people. Further, intestinal florae may alleviate or aggravate HCCs.Methods. To determine which intestinal florae and interleukin aggravate HCCs, we studied the differences in intestinal florae composition and interleukin (IL) indices between HCC patients and healthy people. A total of 64 HCC patients and 24 healthy people were recruited, and their fresh stool samples and serum samples were collected for 16S rRNA sequencing and metabolite index measurement.Results. Data showed that 484 operational taxonomic units (OTUs) and 476 OTUs were detected in the HCC and control groups, respectively. From the phylum level to the species level, 5, 6, 10, 15, 23 and 19 colonies showed differential abundance between the HCC group and healthy people. Moreover, interleukin-6 expression and interleukin-10 expression were significantly different between two groups. Of note, differences of Coriobacterium, Atopobium and Coprococcus at genus level and Veillonella dispar at species level in two groups were significantly related to IL-6 and IL-10.Conclusion. The abundance of intestinal florae in the HCC group was different from the control group. Additionally, combinatorial detection of Coriobacterium, Atopobium and Coprococcus at genus level and V. dispar at species level may be a new method for HCC diagnosis.

Notoginsenoside R1 induces DNA damage via PHF6 protein to inhibit cervical carcinoma cell proliferation.

Notoginsenoside R1 (NGR1), a monomer of Traditional Chinese medicine, is from the Panax notoginsenoside complex, and has been reported to inhibit the proliferation of various types of cancer. However the mechanism underlying NGR1­mediated inhibition of cervical carcinoma cell proliferation remains unclear. Therefore, the current study aimed to investigate the antitumor effects of NGR1 on cervical carcinoma cell lines (CaSki and HeLa cells) in vitro. The Cell Counting Kit­8 and soft agar cell colony formation assay results revealed that NGR1 suppressed the viability and the number colonies of CaSki and HeLa cells, respectively. Furthermore, the DAPI staining, flow cytometry and western blotting results revealed that NGR1 induced cervical carcinoma cell apoptosis, cell cycle arrest in the S phase, upregulation of cyclin A2 and CDK2 expression levels, and downregulation of cyclin D1 expression levels. To further investigate the mechanisms of NGR1, DNA­damage­related proteins, including H2A.X variant histone (H2AX), ATR serine/threonine kinase (ATR) and p53, and the nucleolus protein, plant homeodomain finger protein 6 (PHF6) were analyzed. The results indicated that NGR1 triggered the phosphorylation of H2AX and ATR in a dose­ and time­dependent manner, and downregulated the expression level of PHF6 and upregulated the expression level of p53 in a dose­ and time­dependent manner. In conclusion, the findings of the present indicated that NGR1 may inhibit the viability of cervical carcinoma cells and induce cell apoptosis via DNA damage, which may be activated by the downregulation of PHF6 expression levels, and the subsequent triggering of the phosphorylation of H2AX and ATR. In addition, NGR1 may exert an ability to arrest cervical carcinoma cells in the S phase and upregulate the expression levels of cyclin A2 and CDK2. Therefore, NGR1 may serve as a novel chemotherapeutic agent for cervical carcinoma.

Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction.

Ketamine is a potent dissociative anesthetic and the most commonly used illicit drug. Many addicts are women at childbearing age. Although ketamine has been extensively studied as a clinical anesthetic, its effects on embryonic development are poorly understood. Here, we applied the Xenopus model to study the effects of ketamine on development. We found that exposure to ketamine from pre-gastrulation (stage 7) to early neural plate (stage 13.5) resulted in disruption of neural crest (NC) derivatives. Ketamine exposure did not affect mesoderm development as indicated by the normal expression of Chordin, Xbra, Wnt8, and Fgf8. However, ketamine treatment significantly inhibited Zic5 and Slug expression at early neural plate stage. Overexpression of Zic5 rescued ketamine-induced Slug inhibition, suggesting the blockage of NC induction was mediated by Zic5. Furthermore, we found Notch signaling was altered by ketamine. Ketamine inhibited the expression of Notch targeted genes including Hes5.2a, Hes5.2b, and ESR1 and ketamine-treated embryos exhibited Notch-deficient somite phenotypes. A 15 bp core binding element upstream of Zic5 was induced by Notch signaling and caused transcriptional activation. These results demonstrated that Zic5 works as a downstream target gene of Notch signaling in Xenopus NC induction. Our study provides a novel teratogenic mechanism whereby ketamine disrupts NC induction via targeting a Notch-Zic5 signaling pathway.

Antibiotic resistance and molecular epidemiology of the beta-lactamase-producing Haemophilus influenzae isolated in Chongqing, China.

This study aimed to determine the antibiotic resistance and molecular epidemiology of Haemophilus influenzae isolated from children with acute respiratory infection in Chongqing, China. To this end, 1967 H. influenzae isolates from 2006 to 2009 were analysed regarding ß-lactamase production and antibiotic resistance. Ninety-nine ß-lactamase-producing H. influenzae isolates from 2010 were analysed for antibiotic resistance and promoter regions of bla(TEM) (-1) . ß-lactamase production was found in 35.8% (705/1967) of the strains. All ninety-nine ß-lactamase-producing strains from 2010 were of the TEM-1 type as determined by PCR but did not produce the predicted 1075 bp product. According to PCR-SSCP and DNA sequencing, the promoter regions of bla(TEM) (-1) were categorized into 6 genotypes as SSCP1 (Pdel), SSCP2 (Pa/Pb), SSCP3 (P4), SSCP4 (Prpt.b), SSCP5 (2Prpt) and SSCP6 (P3.b). The Pdel, Pa/Pb and Prpt.b were common promoters of bla(TEM) (-1) for H. influenzae isolated from children in Chongqing. Strains with Prpt.b were more resistant to ampicillin (AMP) than strains with Pdel, Pa/Pb and P4 (p < 0.05). Therefore, bla(TEM-1) ß-lactamase is the main mechanism for resistance of H. influenzae to ampicillin in Chongqing. Furthermore, the Prpt.b promoters may be related to the high resistance of H. influenzae to AMP.