No abstract

Introduction: Glutamine metabolism is essential for the proliferation of cancer cells. Transported by SLC1A5, a Na + dependent transporter, glutamine is absorbed for further use. Recent studies have revealed the anti-tumor effect of berberine. The present study aimed to evaluate the effect of berberine on cancer cell glutamine metabolism. Materials and methods: The inhibitory effect of berberine on liver cancer cells was analyzed by CCK-8 and EdU assay. The glutamine concentrations were detected by ELISA and UHPLC-MRM-MS analysis. Glutamine metabolism-related proteins were determined by Western blot, immunofluorescent analysis and immunohistochemistry. Results: Berberine inhibited the proliferation of Hep3B and BEL-7404 cell in vitro. Berberine suppressed the glutamine uptake by inhibiting SLC1A5. The upregulation of SLC1A5 led to an increased glutamine uptake and improved tolerance to berberine. Berberine suppresses SLC1A5 expression by inhibiting c-Myc. Furthermore, berberine suppresses the growth of tumor xenografts, and the expression of SLC1A5 and c-Myc in vivo. The high expression of SLC1A5 in hepatocellular carcinoma (HCC) tissues is associated with poor prognosis. Conclusion: Berberine can suppress the proliferation of liver cancer cells by reducing SLC1A5 expression.

An argyrophilic technique (AgNOR) was applied to paraffin wax sections of 12 tubular adenomas, 17 villous adenomas with moderate and severe atypia, and 21 colonic adenocarcinomas. The range of the mean number of nucleolar organiser regions (NORS) per nucleus was 1-54-3-28 (99% Cl 229-3 04) for tubular adenomas 3O074-36 (2-98-443), and 360-5O02 (3 74-4 69) for villous adenomas with moderate and severe atypia, respectively, and 5 53-9-33 (6i15-8-54) for highly differentiated adenocarcinomas. The number of AgNORs permitted differentiation among the t-hree groups. The differences observed were significant. Malignant tumour cells were characterised by a large number of AgNORs which were small in size and showed a scattered distribution. Nuclei of tubular adenoma and villous adenoma with moderate atypia had only a small number of large sized AgNORs in a clustered distribution.It is suggested that this method distinguishes malignant epithelial cells from benign cells of colon, even those with severe atypia, and that it is a useful adjunct to diagnostic histopathology. loss of polarity, stratification and an increase in the number of mitotic figures, some of which may be abnormal forms. These features of atypia in villous adenomas vary in severity not only in different tumours but also within the same tumour.Tissues were fixed in 10°o formalin solution and processed to paraffin wax. Sections were cut at 3 gm thickness and submitted to AgNOR staining with slight modification.4 Briefly, sections were dewaxed and taken to water. The reaction mixture was made by dissolving gelatin in 10, aqueous formic acid to make a 1 0 solution. This was mixed with 500/ aqueous silver nitrate solution in a proportion of 1:2. Sections were incubated at room temperature in this mixture for 45 minutes, washed with tap water, taken to xylene and mounted.The AgNORs were seen as dots within the cell nuclei and counted using a x 100 oil immersion lens without previous knowledge of the histological diagnosis. Fields were selected at random and 100 cells were examined using a graticle to prevent recounting. Discrete black dots and dispersed AgNORs in the nuclei were counted and the mean number per nucleus calculated. Student's t test for unpaired data and calculation of 99% confidence interval (CI) was used for statistical analysis. Results TUBULAR ADENOMASThe mean number ofAgNORs per nucleus was 2-67 (range 1 543-28, 99% CI 2 29-3 04)

Translationally controlled tumor protein (TCTP), which is a protein characterized by its potent proliferation promoting activity, has been well studied in the area of growth and tumorigenesis. However, the specific role of TCTP in liver regeneration (LR) and its underlying mechanism remains unclear. In order to investigate the contribution of TCTP during LR, heterozygous TCTP mice were generated, and a mimic LR model was applied to TCTP-knockdown (KD) hepatic cell lines. The results revealed that TCTP-KD impaired LR in mice, and manifested as the following aspects: delayed proliferation of hepatocytes, accompanied by disruption of the mRNA expression of markers of the cell cycle, degenerated lipid metabolism, and abnormal immune response. Furthermore, it was found out that TCTP activated PI3K/AKT signaling by regulating mTORC2. Lastly, the increasing rate of serum TCTP positively correlated to the recovery of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) after liver resection in humans. In summary, the present study is the first to reveal the crucial role of intracellular TCTP in LR.