Conditioned medium from mesenchymal stem cells (MSC-CM) may represent a promising alternative to MSCs transplantation, however, the low concentrations of growth factors in non-activated MSC-CM hamper its clinical application. Recent data indicated that the paracrine potential of MSCs could be enhanced by inflammatory factors. Herein, we pre-activated bone-marrow-derived MSCs under radiation-induced inflammatory condition (MSC^IEC-6(IR)) and investigated the evidence and mechanism for the differential effects of MSC-CM^IEC-6(IR) and non-activated MSC-CM on radiation-induced intestinal injury (RIII). Systemic infusion of MSC-CM^IEC-6(IR), but not non-activated MSC-CM, dramatically improved intestinal damage and survival of irradiated rats. Such benefits may involve the modulation of epithelial regeneration and inflammation, as indicated by the regeneration of intestinal epithelial/stem cells, the regulation of the pro-/anti-inflammatory cytokine balance. The mechanism for the superior paracrine efficacy of MSC^IEC-6(IR) is related to a higher secretion of regenerative, immunomodulatory and trafficking molecules, including the pivotal factor IGF-1, induced by TNF-α, IL-1β and nitric oxide partially via a heme oxygenase-1 dependent mechanism. Together, our findings suggest that pre-activation of MSCs with TNF-α, IL-1β and nitric oxide enhances its paracine effects on RIII via a heme oxygenase-1 dependent mechanism, which may help us to maximize the paracrine potential of MSCs.

Aim The aim of this study was to assess gastric slow waves, antral and duodenal motility simultaneously, and determine the correlation among all these measures in patients with functional dyspepsia. Methods Thirty-one patients with functional dyspepsia were assessed for severity of upper gastrointestinal symptoms with the electrogastrography (EGG) and antroduodenal manometry. The EGG and manometry were recorded for 3 to 4 hours in the fasting state and for 2 hours after a solid meal. Computerized spectral analysis methods were used to compute various EGG parameters. Results The EGG was abnormal in 71.0% of patients. The abnormalities included normal slow waves lower than 70% in the fasting state (51.6% of patients) and in the fed state (48.4% of patients), a decrease in dominant power in 28.9% of patients. Antral motility was abnormal in 80.6% of patients and duodenal motility was abnormal in 74.2% of patients. For the EGG and antral motility, 19 of 31 patients had both abnormal EGG and abnormal antral motility; 2 of 31 patients had both normal EGG and normal antral motility. For the EGG and duodenal motility, these values were 16/31 and 2/31, respectively. By both EGG and antroduodenal manometry, abnormal gastric motor function was found in 93.5% of patients. However, quantitative one-to-one correlation between any of the EGG parameters and the antroduodenal dysmotility was not noted. The patients showed high symptom scores particularly to upper abdominal pain, nausea, and belch. No one-to-one correlation was noted between the symptom scores and any of the EGG or motility parameters. Conclusions More than two-thirds of patients with functional dyspepsia have abnormalities in the EGG and antral/duodenal motility. The sensitivity of these 2 different methods is essentially the same. EGG and antroduodenal manometry can complement each other in demonstrating gastric motor dysfunction in patients with functional dyspepsia.

Objective: PD98059 is a potent and selective inhibitor of mitogen-activated protein kinase. Substantial preclinical evidence has shown an anti-tumor effect of curcumin on various solid tumors. This study aimed to investigate whether curcumin synergistically acts with PD98059 in exerting anti-gastric cancer effects. Methods: The cell counting kit-8 assay was used to detect cell proliferation of the human gastric cancer MGC-803 cell line. Flow cytometry was performed to detect apoptosis. Western blotting was used to detect phosphatase and tensin homolog (PTEN) and phosphorylated Akt (p-Akt) expression levels. Quantitative reverse transcription-polymerase chain reaction was used to determine microRNA-21 (miR-21). Results: A dose of 5 to 40 µM curcumin inhibited proliferation of MGC-803 cells in a dose- and time-dependent manner. A high dose of curcumin strongly inhibited p-Akt protein expression. With increasing curcumin levels, PTEN expression increased and miR-21 levels decreased. These results suggest that curcumin negatively modulated the miR-21/PTEN/Akt pathway. Moreover, after pretreatment with PD98059, cell apoptosis induced by curcumin was significantly increased. Additionally, the inhibitory effects of curcumin on the miR-21/PTEN/Akt pathway were significantly enhanced. Conclusion: PD98059 combined with curcumin may be a potential strategy for managing gastric cancer.

Rationale: The therapeutic benefits of bilirubin in the treatment of ulcerative colitis (UC) are considerable, whereas the underlying mechanism of bilirubin on UC remains unclear remains unexplored. In addition, the weak hydrophilicity and toxicity have limited its translational applications.

Metastasis and recurrence are the challenges of cancer therapy. Recently, mounting evidence has suggested that cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) are critical factors in tumor metastasis and recurrence. The oncogene, Bmi-1, promotes the development of hematologic malignancies and many solid tumors. The aim of the present study was to elucidate the mechanisms through which Bmi-1 promotes the invasion and migration of colon CSCs (CCSCs) using the HCT116 colon cancer cell line. Sphere formation medium and magnetic‑activated cell sorting were used to enrich and screen the CCSCs. CD133 and CD44 were regarded as markers of CCSCs and they were found to be co-expressed in the HCT116 colon cancer cell line. Colony formation assay, cell proliferation assay and viability assay using the Cell Counting Kit-8, and transplantation assay using nude mice injected with CCSCs were used to examine the CCSCs. The CD133+CD44+ HCT116 cells exhibited greater cloning efficiency, an enhanced proliferative ability, increased cell viability and stronger tumorigenicity; these cells were used as the CCSCs for subsequent experiments. In addition, the invasive and migratory abilities of the CD133+CD44+ HCT116 cells were markedly decreased when Bmi-1 was silenced by small interfering RNA (siRNA). The results of RT-qPCR and western blot analysis suggested that Bmi-1 had a negative effect on E-cadherin expression. On the whole, our findings suggest that Bmi-1 promotes the invasion and migration of CCSCs through the downregulation of E-cadherin, possibly by inducing EMT. Our findings thus indicate that Bmi-1 may be a novel therapeutic target for the treatment of colon cancer.