Inhibitory effects of petasin on human colon carcinoma cells mediated by inactivation of Akt/mTOR pathway.

BACKGROUND: Colorectal cancer is the third most common cancer worldwide and still lack of effective therapy so far. Petasin, a natural product found in plants of the genus Petasites, has been reported to possess anticancer activity. The present study aimed to investigate the anticolon cancer activity of petasin both in vitro and in vivo. The molecular mechanism of petasin was also further explored. METHODS: Caco-2, LoVo, SW-620, and HT-29 cell lines were used to detect the inhibitory effect of petasin on colon cancer proliferation. Cell viability was determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was analyzed by flow cytometry. Hoechst 33258 staining was used to visualize morphological changes. Cell migration was assessed using a wound-healing migration assay, and cell invasion was investigated using Transwell chambers. Western blotting assays were employed to evaluate the expression levels of proteins in the protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling pathway. Finally, in vivo activity of petasin was evaluated using the SW-620 subcutaneous tumor model established in Balb/c nude mice. Twelve rats were randomly divided into control group and 10 mg/kg petasin group. The tumor volume was calculated every 7 days for 28 days. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to assess the apoptotic effect of petasin. Differences between two groups were assessed by analysis of independent-sample t tests. RESULTS: Petasin significantly inhibited the proliferation of human colon carcinoma cell lines, induced apoptosis, and suppressed migration and invasion in SW-620 cells. Western blotting results showed that petasin decreased the phosphorylation of Akt (1.01 ±â€Š0.16 vs. 0.74 ±â€Š0.06, P = 0.042), mTOR (0.71 ±â€Š0.12 vs. 0.32 ±â€Š0.11, P = 0.013), and P70S6K (1.23 ±â€Š0.21 vs. 0.85 ±â€Š0.14, P = 0.008), elevated the expression of caspase-3 (0.41 ±â€Š0.09 vs. 0.74 ±â€Š0.12, P = 0.018) and caspase-9 (1.10 ±â€Š0.27 vs. 1.98 ±â€Š0.22, P = 0.009), decreased the Bcl-2 protein (2.75 ±â€Š0.47 vs. 1.51 ±â€Š0.36, P = 0.008), downregulated the expression of matrix metalloproteinase (MMP)-3 (1.51 ±â€Š0.31 vs. 0.82 ±â€Š0.11, P = 0.021) and MMP-9 (1.56 ±â€Š0.32 vs. 0.94 ±â€Š0.15, P = 0.039) in SW-620 cell. In vivo, 10 mg/kg petasin inhibited tumor growth in Balb/c nude mice (924.18 ±â€Š101.23 vs. 577.67 ±â€Š75.12 mm at day 28, P = 0.001) and induced apoptosis (3.6 ±â€Š0.7% vs. 36.0 ±â€Š4.9%, P = 0.001) in tumor tissues. CONCLUSIONS: Petasin inhibits the proliferation of colon cancer SW-620 cells via inactivating the Akt/mTOR pathway. Our findings suggest petasin as a potential candidate for colon cancer therapy.

Prokinetic activity of Prunus persica (L.) Batsch flowers extract and its possible mechanism of action in rats.

The peach tree, Prunus persica (L.) Batsch, is widely cultivated in China, and its flowers have been used for centuries in traditional Chinese medicine to treat gut motility disorders. But few studies have explored the pharmacological effect of Prunus persica (L.) Batsch flowers on gastrointestinal motility. In this study, the activities of different extracts from Prunus persica (L.) Batsch flowers on the smooth muscle contractions were evaluated using isolated colon model, and the ethyl acetate extract (EAE) showed the strongest effects in vitro. EAE (10(-8)-10(-5) g/mL) caused a concentration-dependent stimulatory effect in rat colonic tissue. Additionally, ketotifen (100 µM), cimetidine (10 µM), and pyrilamine (1 µM) produced a significant inhibition of contractions caused by EAE. Furthermore, immunofluorescence and toluidine blue staining revealed increased numbers of mast cells in the EAE group, and EAE increased histamine release from the colonic tissues. These data indicate that EAE has significant prokinetic activity and acts by a mechanism that mainly involves mast cell degranulation. Our study provides a pharmacological basis for the use of an extract of Prunus persica (L.) Batsch flowers in the treatment of gut motility disorders.

Effect of music in endoscopy procedures: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Endoscopies are common clinical examinations that are somewhat painful and even cause fear and anxiety for patients. We performed this systematic review and meta-analysis of randomized controlled trials to determine the effect of music on patients undergoing various endoscopic procedures. METHODS: We searched the Cochrane Library, Issue 6, 2013, PubMed, and EMBASE databases up to July 2013. Randomized controlled trials comparing endoscopies, with and without the use of music, were included. Two authors independently abstracted data and assessed risk of bias. Subgroup analyses were performed to examine the impact of music on different types of endoscopic procedures. RESULTS: Twenty-one randomized controlled trials involving 2,134 patients were included. The overall effect of music on patients undergoing a variety of endoscopic procedures significantly improved pain score (weighted mean difference [WMD] = -1.53, 95% confidence interval [CI] [-2.53, -0.53]), anxiety (WMD = -6.04, 95% CI [-9.61, -2.48]), heart rate (P = 0.01), arterial pressure (P < 0.05), and satisfaction score (SMD = 1.83, 95% CI [0.76, 2.91]). Duration of the procedure (P = 0.29), except for gastrointestinal endoscopy (P = 0.03), and sedative or analgesic medication dose (P = 0.23, P = 0.12, respectively) were not significantly decreased in the music group, compared with the control group. Furthermore, music had little effect for patients undergoing colposcopy and bronchoscopy in the subanalysis. CONCLUSION: Our meta-analysis suggested that music may offer benefits for patients undergoing endoscopy, except in colposcopy and bronchoscopy.

Ghrelin suppression and fat loss after left gastric artery embolization in canine model.

PURPOSE: To evaluate the effects of left gastric artery embolization (LGAE) on plasma ghrelin levels, abdominal fat, and body weight in beagles. METHODS: The institutional animal care and use committee approved this study. Fifteen healthy adult beagles (12 male and three female animals) were randomly divided into three experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A(5) hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B). Transcatheter saline injections in the left gastric artery were performed as a control. Weight and fasting plasma ghrelin levels were obtained at baseline and at weekly intervals for 8 weeks after the procedure in all animals. All animals were scanned and measured by multidetector computed tomography at baseline and at week 8 for evaluation of abdominal fat. RESULTS: In LGAE-treated animals, plasma ghrelin and body weight significantly decreased compared to control animals (group A: P = 0.007 and P = 0.000; group B: P = 0.004 and P = 0.000, respectively). Subcutaneous fat size was also significantly reduced (P = 0.011 and P = 0.027 for groups A and B, respectively). The decreasing percentage in ghrelin levels at week 6 (peak of recovery) of LGAE-treated animals were negatively correlated with the size of area supplied by left gastric artery (r = -0.693, P = 0.026). CONCLUSION: LGAE could suppress the plasma concentration of ghrelin, which results in subcutaneous fat size reduction and weight loss. Compensatory ghrelin production might occur in the remnant gastric fundus after LGAE.

[Effect of early enteral nutrition supplemented with glutamine on postoperative intestinal mucosal barrier function in patients with gastric carcinoma].

OBJECTIVE: To investigate the effect of early enteral nutrition (EEN) supplemented with glutamine on postoperative intestinal mucosal barrier function of patients with gastric carcinoma. METHODS: Eighty patients with gastric carcinoma who underwent intraoperative peritoneal hyperthermic chemotherapy(IPHC) were randomized into two groups: EEN+glutamine (EEN+Gln) group(n=40) and EEN group(n=40). Intestinal mucosal barrier function was evaluated by serum diamine oxidase (DAO), ratio of lactulose to mannitol(L/M), endotoxin lipopolysaccharides(LPS), and tumor necrosis factor-α(TNF-α) at 1 day before operation, 1 day, 7 days, 12 days after operation. Time to first flatus and tolerance to EEN were recorded as well. RESULTS: There were no significant differences in the two groups in demographics(all P>0.05). Two cases(5%) in the EEN+Gln group and 1 case (2.5%) in the EEN group could not tolerate well(P>0.05). On postoperative day 1, there were no differences in serum DAO, L/M ratio, LPS, TNF-α between the two groups (P>0.05). On postoperative day 7, all the parameters for mucosal barrier function were significantly lower in the EEN+Gln group. On postoperative day 12, the urinary L/M and DAO, LPS, and TNF-α were still significantly lower in the EEN+Gln group, however, urinary L/M was comparable between the two groups. There were no differences between the two groups in the time to first flatus (P>0.05). CONCLUSION: The immunologic tolerance of enteral nutrition supplemented with glutamine is favorable, which provides protective effect on intestinal mucosal barrier in patients with gastric carcinoma undergoing IPHC.

[Nutritional therapy of duodenocutaneous fistula].

OBJECTIVE: To summarize the experience in nutritional support for the management of duodenocutaneous fistula. METHODS: Data of 32 patients with duodenocutaneous fistula in Zhejiang provincial people's hospital from January 1999 to December 2009 were analyzed retrospectively. RESULTS: The mean duration of nutritional support was 35.6 days (range, 8-82 days). Eight received total parenteral nutrition, 2 total enteral nutrition, and 22 parenteral nutrition combined with enteral nutrition respectively. Succus entericus reinfusion with enteral nutrition was used in 11 cases, glutamine-enriched nutritional support in 28 cases, somatostatin in 12 cases. In these patients, the healing rate was 75.0% after conservative treatment. In the 8 patients who underwent surgery, 6 were cured and 2 died (due to severe abdominal infection and multiple organ failure). A total of 30 patients had the fistulas cured and discharged. CONCLUSIONS: Parenteral nutrition combined with enteral nutrition, succus entericus reinfusion combined with enteral nutrition, glutamine-enriched nutritional support and somatostatin are important factors for the healing of duodenocutaneous fistulas.

Global analysis of gene expression profiles in Brassica napus developing seeds reveals a conserved lipid metabolism regulation with Arabidopsis thaliana.

In order to study Brassica napus fatty acid (FA) metabolism and relevant regulatory networks, a systematic identification of fatty acid (FA) biosynthesis-related genes was conducted. Following gene identification, gene expression profiles during B. napus seed development and FA metabolism were performed by cDNA chip hybridization (>8000 EST clones from seed). The results showed that FA biosynthesis and regulation, and carbon flux, were conserved between B. napus and Arabidopsis. However, a more critical role of starch metabolism was detected for B. napus seed FA metabolism and storage-component accumulation when compared with Arabidopsis. In addition, a crucial stage for the transition of seed-to-sink tissue was 17-21 d after flowering (DAF), whereas FA biosynthesis-related genes were highly expressed primarily at 21 DAF. Hormone (auxin and jasmonate) signaling is found to be important for FA metabolism. This study helps to reveal the global regulatory network of FA metabolism in developing B. napus seeds.