The effects of the oral administration of graphene oxide on the gut microbiota and ultrastructure of the colon of mice.

Background: Graphene oxide (GO) has been widely used in the field of biomedicine and has shown great potential in drug delivery. Oral administration is an important mode of administration, but there are few studies on the effects of oral GO on gastrointestinal tract and gut microbiota. This study sought to explore the effects of oral GO on the gastrointestinal tract and gut microbiota. Methods: In total, 20 C57BL/6 male mice, aged 5 weeks old, were randomly divided into the following 4 groups (n=5): the control group, the GO30 group, the GO60 group, and the GO120 group. The GO sample solution was administered intragastrically at the doses of 30, 60, or 120 mg/kg every 3 days, and the control group was given an equal volume of distilled water. On the 16th day, mouse feces were taken for 16S ribosomal ribonucleic acid (rRNA) sequencing analysis, and the mice were dissected, and the heart, liver, kidney, and colon removed for histological analysis. Additionally, the ultrastructure of the colon was observed by transmission electron microscopy. Results: No obvious damage was observed in the hearts, livers, and kidneys of the mice. However, the intestinal ultrastructure of the mice in the GO group was damaged. The main manifestations were an uneven arrangement and local atrophy of the microvilli, swelling of the mitochondria and endoplasmic reticulum, and the widening of the intercellular spaces. The damage was positively correlated with increasing GO doses. The 16S rRNA sequencing results showed that the structure of the gut microbiota in the GO group was altered, and the contents of Alistipes, Enterobacteriaceae, Eubacterium, and Xanthobacteraceae were decreased. Conclusions: The oral administration of GO had no obvious toxicity effects on the hearts, livers, and kidneys of the mice. However, it did destroy the ultrastructure of the mouse colon and shift the structure of the gut microbiota, decreasing the contents of Alistipes, Enterobacteriaceae, Eubacterium, and Xanthobacteraceae.

Graphene oxide induces autophagy and apoptosis via the ROS-dependent AMPK/mTOR/ULK-1 pathway in colorectal cancer cells.

Aim: To investigate the anticancer effects and action mechanism of graphene oxide (GO) in colorectal cancer (CRC). Materials & methods: Anticancer effects and mechanisms of GO in CRC were investigated both in vivo and in vitro. Results: GO significantly inhibited tumor growth both in vitro and in vivo. GO was able to enter HCT116 cells through endocytosis. GO treatment resulted in cytotoxicity, reactive oxygen species (ROS) production, apoptosis, autophagy and activation of the AMPK/mTOR/ULK1 signal pathway. However, ROS scavenger N-acetylcysteine (NAC) attenuated the above effects and restored the effects of GO on protein expressions related to apoptosis, autophagy and AMPK/mTOR/ULK1 signal pathways. Conclusion: GO exerts anticancer effects against CRC via ROS-dependent AMPK/mTOR/ULK-1 pathway-related autophagy and apoptosis.

LncRNA SNHG16 induces the SREBP2 to promote lipogenesis and enhance the progression of pancreatic cancer.

Aim: Blocking lipogenesis could significantly inhibit the progression of pancreatic cancer. Exploring the regulatory mechanisms of lipogenesis by lncRNA SNHG16 might be of great significance to control the development of pancreatic cancer. Methods: The proliferation, migration, invasion and lipogenesis were determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, transwell and Oil Red O staining assays, respectively. The interactions among lncRNA SNHG16, miR-195 and SREBP2 were analyzed by dual luciferase reporter assays. Results: Both the knock down of lncRNA SNHG16 and SREBP2 and overexpression of miR-195 suppressed the proliferation, migration, invasion and lipogenesis in pancreatic cancer cells. LncRNA SNHG16 directly sponged miR-195 to modulate the lipogenesis via regulating the expression of SREBP2. Conclusion: LncRNA SNHG16 accelerated the development of pancreatic cancer and promoted lipogenesis via directly regulating miR-195/SREBP2 axis.

Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats.

AIM: To observe the protective effect of glucagon-like peptide-2 (GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect. METHODS: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase (ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14(th) day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A (IgA) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group. RESULTS: In the rat model, jaundice was obvious, and the rats' activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced IgA expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group (P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group (P < 0.01). CONCLUSION: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal IgA and reduced bilirubin and endotoxin.