Effect of Daikenchuto On Spontaneous Intestinal Tumors in ApcMin/+ Mice.

Daikenchuto (TU-100) is herbal medicine which predominantly contains ginger, Japanese pepper, and ginseng. We investigated whether TU-100 can affect the composition of gut flora and intestinal tumor development using ApcMin/+ mice, a murine model of intestinal tumor. Bacterial 16S rRNA sequencing and short-chain fatty acid analysis were performed on faecal samples. Tumor number and size were analysed. Any change in gene expression of the tumor tissues was assessed by real-time PCR. Principal coordinate analysis (PCoA) showed that the faecal microbiota cluster of TU-100-fed mice was different from the microbiota of control mice. However, no significant difference was observed in the concentration of short-chain fatty acids, tumor number, and gene expression levels between the two groups. Our data showed that TU-100 can affect the intestinal environment; however, it does not contribute in tumor progression or inhibition in our setting.

Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice.

PURPOSE: Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. METHODS: KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. RESULTS: Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. CONCLUSIONS: Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

Celastrol inhibits growth and metastasis of human gastric cancer cell MKN45 by down-regulating microRNA-21.

Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA-21 (miR-21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up-regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR-21 overexpression (p < .05 or p < .01). On the other side, miR-21 silence showed contrary results (p < .05) as relative to miR-21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down-regulating miR-21.

The Relationship between RUNX3 Expression, Nursing Strategies and Nutritional Status in Elderly Patients with Advanced Gastric Cancer.

BACKGROUND: The aim of this study was to explore the relationship between nutritional status and expression of RUNX3 in gastric cancer cells and to investigate the effects of nursing strategies on the nutritional status of elderly patients with advanced gastric cancer. METHODS: Forty-eight elderly patients admitted at Affiliated Hospital of Qingdao University with advanced gastric cancer and 30 healthy controls were selected as subjects from 2014-15. The correlation between RNX3 gene expression and nutritional status of the gastric cancer patients was investigated. The patients with advanced gastric cancer who had low expression of RUNX3 gene were treated with holistic nursing while routine nursing was taken for those patients who had normal or high expression of RUNX3 gene. The nutritional statuses of these patients were evaluated after 3 months of nursing. After a follow-up of 1 year, the influence of different nursing methods on the survival time was evaluated. RESULTS: Compared with normal gastric tissue, the expression of RUNX3 gene and protein in tissues of advanced gastric cancer were significantly decreased (P<0.01). Compared with patients with normal or high expressions of RUNX3, the nutritional statuses of advanced gastric cancer patients with low expressions of RUNX3 were lower (P<0.01). The nutritional statuses of patients with low expressions of RUNX3 were notably improved after holistic nursing, becoming equivalent to those with normal or high expression of RUNX3 who received routine nursing (P>0.05). The survival time of patients with low expression of RUNX3 who received holistic nursing were similar to patients with normal or high expression of RUNX3 who received routine nursing (P>0.05). CONCLUSION: RUNX3 is correlated with the occurrence and development of advanced gastric cancer. The low nutritional status of elderly advanced gastric cancer patients with low expressions of RUNX3 can be significantly enhanced by holistic nursing, thereby prolonging survival time.

[Association of gastric emptying with ghrelin, obestatin and receptor (GHSR, GPR-39) in hypothalamus of diabetic rats].

OBJECTIVE: To investigate the association of gastric emptying with ghrelin, obestatin and GHSR, GPR-39 in hypothalamus of diabetic rats. METHODS: Sixty Wistar rats were randomly divided into three groups: a normal control group (NC, n = 20), a diabetes mellitus group (DM, n = 20) induced by intraperitoneal injection of streptozotocin (STZ) and an insulin treated group (INS, n = 20). After two and six weeks of STZ injection, gastric emptying was measured by intragastric administration of phenol red, ghrelin and obestatin in hypothalamus measured by ELISA (enzyme-linked immunosorbent assay) and GHSR and GPR-39 by RT-PCR (reverse transcription-polymerase chain reaction). RESULTS: After two weeks of STZ injection, gastric emptying (%) (74 +/- 8, 40 +/- 5), ghrelin level(ng/g) (52 +/- 9, 51 +/- 7) and ratio of ghrelin/obestatin (3.8 +/- 1.0, 2.8 +/- 1.0) increased significantly in DM and INS groups compared to those in NC group [32% +/- 7%, (39 +/- 11) ng/g, 2.1 +/- 0.8, all P < 0.05]. Obestatin level(ng/g) (14.2 +/- 2.0) of hypothesis decreased significantly in DM group as compared to those in NC group (21.7 +/- 4.7) while GHSR/beta-actin increased significantly (1.26 +/- 0.46 vs 0.77 +/- 0.21, P < 0.05). Gastric emptying was positively correlated with ghrelin, ghrelin/obestatin and GHSR/beta-actin of hypothalamus (r = 0.49; r = 0.63; r = 0.73; P < 0.01). But there was a negative correlation with obestatin of hypothalamus (r = -0.74, P < 0.01). After six weeks of STZ injection, gastric emptying (78.97% +/- 8.13% vs 44.06% +/- 5.06%) increased significantly in DM and INS groups as compared to those in NC group (35.06% +/- 3.91%, P < 0.01). Gastric emptying was positively correlated with ghrelin/obestatin of hypothalamus (r = 0.40, P < 0.05). There was no detection of GPR-39 in hypothalamus. CONCLUSION: The rapid gastric emptying may be due to the rising levels of ghrelin and GHSR in hypothalamus during early hyperglycemia. And the duration of hyperglycemia is affected by the rising ratio of ghrelin/obestatin.

[Effects of lactation, lactation-cessation and lactation-cessation-lactation paradigms on hypothalamic orexin-A immunoreactive neurons in rats].

Orexin-A is a novel neuropeptide produced by neurons mainly located in lateral hypothalamic area that potently facilitates appetite and food intake. The purpose of this study was to investigate the possible change in orexin-A immunoreactivity in suckling-induced hyperphagia. By using immunohistochemistry and image analysis techniques we examined orexin-A-like immunoreactivity in a series of rat brain sections corresponding to the hypothalamus in groups of non-lactating, lactating, lactating with overnight cessation of suckling, lactating and cessation followed by resumed short-term sucklings. Long-term lactation significantly increased daily food intake on day 3 (81%) and day 11 (180%) postpartum compared to that in non-lactating postpartum rats, whereas daily food intake was significantly decreased by overnight cessation of suckling on day 11 postpartum in long-term lactating rats (45%). Moreover, long-term lactating rats on day 12 postpartum exhibited significantly greater number and higher mean staining intensity of orexin-A immunoreactive neurons than those of non-suckling postpartum rats (P<0.001 and P<0.05, respectively). Overnight cessation of lactation in rats on day 12 postpartum significantly decreased both the number and mean staining intensity of orexin-A immunoreactive neurons compared to those in long-term lactating group of rats (P<0.001 and P<0.05, respectively), similar to the levels in the non-lactating postpartum rats. Resumed lactation for 2 and 5 h after overnight cessation of lactation significantly increased the number (P<0.001 and P<0.05, respectively) and mean staining intensity (P<0.05) of orexin-A immunoreactive neurons compared to those in the rats without resumed lactation. Both long-term lactation and short-term resumed suckling enhanced orexin-A immunoreactivity in the hypothalamus in rats, and overnight cessation of lactation down-regulated the increased orexin-A immunoreactivity induced by long-term lactation. Suckling may regulate orexin-A expression in the hypothalamus and the increased orexin-A may be involved in hyperphagia in lactating rats, suggesting the possibility of the existence of some neural-humoral links between suckling and hypothalamic orexin-A-immunoreactive neurons.

Effects of Zhaoyangwan on chronic hepatitis B and posthepatic cirrhosis.

AIM: To study the therapeutic effects of zhaoyangwan (ZYW) on chronic hepatitis B and hepatic cirrhosis and the anti-virus, anti-fibrosis and immunoregulatory mechanisms of ZYW. METHODS: Fifty cases of chronic hepatitis B and posthepatic cirrhosis with positive serum HBsAg, HBeAg, anti-Hbc and HBV-DNA were divided randomly and single-blindly into the treatment group (treated with ZYW) and the control group (treated with interferon). After 3 month treatment, the effects of the treatment group and the control group were evaluated. RESULTS: The serum ALT normalization was 83.3% (30/36) in the treatment group and 85.7% (12/14) in the control group, with no significant difference (chi2=0.043, P>0.05). After the course, the negative expression rates of the serum HBV-DNA and HBeAg were 44.4% (16/36) and 50% (18/36) in the treatment group, and 50% (7/14) and 50% (7/14) in the control group, respectively, with no significant difference (chi2=0.125, chi2=0.00, both P>0.05). Negative HBsAg and positive HBsAb appeared in 4 cases of the treatment group and 1 case of the control group. Serum anti-HBc turned negative in 6 cases of the treatment group and 1 case of the control group, respectively. After the ZYW treatment, serum CD3+, CD4+, CD8+, CD4+/CD8+ and NK cell activation were significantly increased. Only serum CD3+ and NK cell activation were significantly increased in the control group with a significant difference between the two groups. The serum C4, C1q, C3, B and C9 were significantly increased in the treatment group. In the control group only the serum C4 was increased. The concentration of serum interferon had no change after treatment with ZYW, while it was significantly increased in the control group after treatment with interferon. The ultrastructure of the liver restored, which helped effectively to reduce the degeneration and necrosis of hepatic cells,infiltration of inflammatory cells and hepatic cirrhosis. CONCLUSION: ZYW is a pure Chinese herbal medicine. It can exert potent therapeutic effects on chronic hepatitis B and posthepatic cirrhosis. ZYW has similar therapeutic effects to those of interferon. It is cheap and easily administered with no obvious side-effects. It can be widely used in clinical practice.