Resveratrol alleviates inflammatory bowel disease by inhibiting JAK2/STAT3 pathway activity via the reduction of O-GlcNAcylation of STAT3 in intestinal epithelial cells.

The role of O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) in the pathogenesis of inflammatory bowel disease (IBD) has been increasingly highlighted in recent studies. It's been reported that signal transducer and activator of transcription 3 (STAT3) O-GlcNAcylation can affect the activity of the Janus kinase2 (JAK2)/STAT3 pathway.Our recent study showed that resveratrol repairsIBDin mice.On this basis,the present study aimed to explore whether the mechanism of IBD repair by resveratrol is associated with STAT3 O-GlcNAcylation. Pretreatment of colitis mice and intestinal epithelial cells with an O-GlcNAcylation promoter (Thiamet G, or Glucosamine) and an O-GlcNAcylation inhibitor (OSMI-1) showed that increased O-GlcNAcylation promoted colitis in mice.The pro-inflammatory cytokines interleukin (IL) -6, IL-1ß, and tumor necrosis factor-α (TNF-α) were increased, while the anti-inflammatory cytokine IL-10 was decreased. Moreover, the downstream target proteins of JAK2/STAT3, cyclooxygenase-2 and nitric oxide synthase 2 were up-regulated, Resveratrol treatment mitigated the inflammation by decreasing JAK2/STAT3 activity, as well as STAT3 O-GlcNAcylation. Finally, the correlation between STAT3 glycosylation and phosphorylation in intestinal epithelial cells under the effect of resveratrol was investigated by Immunofluorescence co-localization and immunoprecipitation.The results showed that resveratrol inhibited STAT3 O-GlcNAcylation, thereby inhibiting its phosphorylation, reducing JAK2/STAT3 pathway activity, and alleviating IBD.

Expression and potential role of FOSB in glioma.

Background: FOSB is reported to be an oncogene in a variety of tumors. However, the expression and role of FOSB in glioma remain obscure. In this study, we aimed to explore the expression of FOSB in glioma and its biological role in glioblastoma multiforme (GBM). Methods: Western blot, immunohistochemical staining, and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression of FOSB in clinical samples. FOSB was knocked down in cells to determine the effects of FOSB on the phenotypic changes of tumors by plate cloning, CCK-8 assay, and Transwell assay. Finally, subcutaneous tumorigenesis in nude mice was used to observe the tumorigenesis of glioma cell lines after the knockdown of the FOSB gene. Results: FOSB expression was higher in glioma compared with normal brain tissue. After the downregulation of FOSB, the expression of cleaved caspase-3 increased. Plate cloning and CCK-8 experiments showed that the proliferation of glioma cell lines decreased. The Transwell assay demonstrated that the glioblastoma cell lines had lower migration ability after the knockdown of FOSB. Finally, the tumor volume of U87 glioma cells in group sh-FOSB was smaller than that in the control group. The TUNEL staining in vitro showed that the apoptosis of sh-FOSB glioma cells increased. Conclusion: FOSB was highly expressed in glioma tissues. The viability of glioma cells decreased, and the ability of glioma cells to proliferate and migrate was reduced when FOSB was downregulated. Hence, FOSB may promote the development and migration of gliomas.

FOXO4 expression associates with glioblastoma development and FOXO4 expression inhibits cell malignant phenotypes in vitro and in vivo.

BACKGROUND AND AIM: Forkhead box protein O4 (FOXO4) is a transcription factor, and aberrant FOXO4 expression is associated with development of various human cancers. This study explored the role of FOXO4 in glioma in vitro and in vivo. METHODS: FOXO4 expression was first assessed in normal brain tissues, low-grade glioma, glioblastoma multiforme (GBM), normal human astrocytes (HA), and GBM cell lines, while manipulation of FOXO4 expression in glioma cell lines was assessed using qRT-PCR, Western blot, and cell viability CCK-8, Transwell, and a nude mouse subcutaneous xenograft assays. KEY FINDINGS: The data showed downregulated FOXO4 expression in GBM tissues and cell lines. FOXO4 overexpression induced by transfection with FOXO4 cDNA significantly inhibited GBM cell proliferation, migration, and invasion, but increased tumor cells to undergo apoptosis in vitro, while suppressed growth of GBM cell subcutaneous xenografts in nude mice. In conclusion, FOXO4 possesses an anti-cancer glioma activity, which could be a novel target for future control of GBM.

Prolonged adjuvant capecitabine chemotherapy improved survival of stage IIIA gastric cancer after D2 gastrectomy.

GOALS: This study aims to investigate the safety and efficacy of prolonged adjuvant capecitabine chemotherapy on survival of gastric cancer after D2 gastrectomy. BACKGROUND: Inadequate evidence is available on optimal duration of chemotherapy and the number of administered cycles is generally based on patient responsiveness and individual tolerability as well as physician preferences. STUDY: We randomly assigned 307 gastric cancer patients after D2 gastrectomy between January 2006 and December 2010 to XELOX group and Prolonged group. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130mg/mg on day 1 and oral capecitabine 1000mg/m(2) twice daily on days 1-14 of a 3-week cycle for eight cycles in half a year. In Prolonged group, patients underwent extra oral capecitabine 1000mg/m(2) twice daily on days 1-14 of a 3-week cycle for eight cycles after eight cycles of XELOX. The disease-free survival and overall survival were compared. RESULTS: Significant differences were found in 3-year disease-free survival (Prolonged group 56.6%, XELOX group 48.4%, P=0.0357). Subgroup analysis by TNM staging showed that patients with stage IIIA gastric cancer in the Prolonged group had significantly higher DFS (50.00% vs 40.96, P=0.0178) and OS (71.95% vs 57.83, P=0.0230) than that of patients in the XELOX group. No grade 4 adverse effects or treatment-related deaths were reported. More patients in the Prolonged group experienced hand-foot syndrome than in the XELOX group. CONCLUSIONS: Prolonged capecitabine chemotherapy prevents improves the prognosis of patients with stage IIIA gastric cancer after D2 gastrectomy.

Hepatic arterial infusion chemotherapy reduced hepatic metastases from pancreatic cancer after pancreatectomy.

BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases from pancreatic cancer after pancreatectomy. METHODOLOGY: We randomly assigned 106 patients with pancreatic cancer after pancreatectomy between 2005 and 2010 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (Combined Therapy) or 6 cycles of systemic chemotherapy alone (Monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 5-hour infusion of 5-fluorouracil 1000 mg/m2 on day 1 followed by gemcitabine 800 mg/m2 as an over 30-min infusion on day 1 and day 8. The treatment was started on an average of 21.2 days after surgery and repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year overall survival (Combined Therapy, 23.08 %; Monotherapy, 14.81%; P=0.0473) and liver metastases-free survival (Combined Therapy, 80.77%; Monotherapy, 55.56%; P=0.0014). CONCLUSIONS: HAIC effectively and safely prevents liver metastases and improves the prognosis of patients with pancreatic cancer after pancreatectomy.

Optimal selection of methods for mini-invasive treatment of extrahepatic bile duct stones.

BACKGROUND/AIMS: This study aims to identify the optimal mini-invasive treatment for extrahepatic bile duct stones. METHODOLOGY: One hundred and seventy eight patients with EHBD stones were randomized into 4 groups: laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) plus T-tube drainage (group LT), LC and LCBDE with endonasobiliary drainage (ENBD) tube (group LE), and endoscopic sphincterotomy with ENBD followed by LC (group EE) and T-tube drainage of open CBDE (group OT). Demographic data, perioperative findings, postoperative outcomes, hospital expense, gastrointestinal quality of life index (GIQLI) scores and cost per quality-adjusted life year (QALY) were analyzed. RESULTS: The operating time was longest in group EE. There was less bleeding in group OT and EE. Group LE and EE had shorter hospital stay and recovery time of intestinal motility. The postoperative white blood cell count and serum C-reaction protein level were higher in group LT and OT. Postoperatively, the mean GIQLI scores in group LE and EE were higher. Mean cost were highest in group EE. Patients in group LE had lowest cost per QALY. CONCLUSIONS: The modified laparoscopic procedure, LC combined with LCBDE followed by a primary closure over the ENBD tubes, appears to be the best option for patients with EHBD stones.

Spleen-preserving distal pancreatectomy or distal pancreatectomy with splenectomy?: Perioperative and patient-reported outcome analysis.

GOALS: We designed this study to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. BACKGROUND: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. STUDY: From January 2005 to July 2009, 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: There were no significant differences in demographics, final diagnoses, estimated blood loss, intraoperative transfusion, and operative time between the 2 groups. More perioperative complications occurred in the DPS group than in the SPDP group (P=0.0344). Consequently, postoperative hospital stay was significantly shorter in the SPDP group than in the DPS group (P=0.0273). In the follow-up survey, episodes of common cold or flu were apparently more frequent in the DPS group (P=0.047). More patients in the DPS group felt fatigue (P=0.0481) and poor health condition (P=0.0371). Less newly developed (P=0.0193) and aggravated diabetes mellitus (P=0.0361) were also observed in the SPDP group. Platelet counts on postoperative day (POD) 5, hemoglobin on POD 3, WBC counts, and CRP level on POD 2 were significantly higher in the DPS group than in the SPDP group and these differences continued to be significant for months after surgery. CONCLUSIONS: In addition to frequent higher grade complications, prolonged hospital stays, and severe hematological abnormalities, DPS seemed to result in poor health condition based on the follow-up survey. Even an effort to preserve an adult spleen in distal pancreatectomy is worthwhile.

Spleen-preserving distal pancreatectomy: perioperative and long-term outcome analysis.

BACKGROUND/AIMS: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. We aimed to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. METHODOLOGY: 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: There were no significant differences in demographics, final diagnoses estimated blood loss, intraoperative transfusion and operative time between the two groups. More perioperative complications occurred in DPS group than in the SPDP group (p = 0.0344). Consequently, postoperative hospital stay was significantly shorter in SPDP group than in DPS group (p = 0.0273). On the follow-up survey, episodes of common cold or flu were apparently more frequent in the DPS group (p = 0.047). More patients in the DPS group felt fatigue (p = 0.0481) and poorer health condition (p = 0.0371). Less newly developed (p = 0.0193) and aggravated diabetes mellitus (p = 0.0361) were also observed in SPDP group. CONCLUSIONS: In addition to frequent higher-grade complications, and prolonged hospital stays, DPS appeared to result in poorer health condition based on follow-up survey. Even an effort to preserve adult spleen in distal pancreatectomy is worthwhile.

[Dual regulation effect of somatostatin on immunity in patients with severe sepsis caused by abdominal diseases].

OBJECTIVE: to investigate the effect of somatostatin on inflammatory immune disorders and prognosis in patients with severe sepsis caused by abdominal diseases. METHODS: fifty-three patients with severe abdominal sepsis (age > 18 years, APACHE-II score > 15) from June 2005 to June 2009 were randomly divided into Somatostatin group (n = 23) and SSC Group (n = 30). Fifteen healthy volunteers of the same age range were chosen as Control group. The SSC group was treated with classical SSC therapy, and the Somatostatin Group was treated with the same regime plus 14-peptide somatostatin continuous infusion at the dose of 6 mg/24 h for 7 days. The serum levels of interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) were determined by using ELISA. CD(4)(+), CD(8)(+) T cell subsets were determined by fluorescence activated cell sorter(FACS) and CD(4)(+)/CD(8)(+) was calculated. APACHE-II score was observed on admission (d1) and day 3, 7 and 14 after treatment. Morality rates in 28 days in two groups were recorded. RESULTS: compared with Control group, IL-10 and TNF-α levels were significantly elevated in patients with severe abdominal sepsis (P < 0.05), while CD(4)(+), CD(8)(+) T cell and CD(4)(+)/CD(8)(+) decreased significantly (P < 0.05). Compared with the Somatostatin group CD(4)(+), CD(8)(+) T cell and CD(4)(+)/CD(8)(+) on d7 and d14 in SSC Group were significantly increased (P < 0.05), while IL-10 and TNF-α decreased significantly(P < 0.05). APACHE-II scores on d3, d7, d14 of Somatostatin group were significantly lower than those of SSC group, and 28 d mortality rate also declined. CONCLUSIONS: in patients with severe abdominal sepsis, systemic inflammatory response and immune suppression exist simultaneously. Somatostatin has a dual immunomodulatory activity in these patients.