Background and purpose: Rheumatoid arthritis (RA) is an autoimmune disorder involving subsets of activated T cells, in particular T helper (Th) 1 and Th17 cells, which infiltrate and damage tissues and induce inflammation. Prostaglandin E2 (PGE2) enhances the Th17 response, exacerbates collagen-induced arthritis (CIA) and promotes inflammatory pain. The current study investigated whether selective antagonism of the PGE2 EP4 receptor would suppress Th1/Th17 cell development and inflammatory arthritis in animal models of RA. Experimental approach: Effects of PGE2 and a novel EP4 receptor antagonist ER-819762 on Th1 differentiation, interleukin-23 (IL-23) production by dendritic cells (DCs), and Th17 development were assessed in vitro. The effect of ER-819762 was evaluated in CIA and glucose-6-phosphate isomerase (GPI)-induced arthritis models. In addition, the effects of ER-819762 on pain were evaluated in a model of chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the rat. Key results: Stimulation of the EP4 receptor enhanced Th1 differentiation via phosphatidylinositol 3 kinase signalling, selectively promoted Th17 cell expansion, and induced IL-23 secretion by activated DCs, effects suppressed by ER-819762 or anti-PGE2 antibody. Oral administration of ER-19762 suppressed Th1 and Th17 cytokine production, suppressed disease in collagen-and GPI-induced arthritis in mice, and suppressed CFA-induced inflammatory pain in rats. Conclusion and implications: PGE2 stimulates EP4 receptors to promote Th1 differentiation and Th17 expansion and is critically involved in development of arthritis in two animal models. Selective suppression of EP4 receptor signalling may have therapeutic value in RA both by modifying inflammatory arthritis and by relieving pain.

Previous studies have evidenced that the anticancer potential of curcumin (diferuloylmethane), a main yellow bioactive compound from plant turmeric was mediated by interfering with PI3K/Akt signaling. However, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that curcumin treatment reduced Akt protein expression in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells, along with an activation of autophagy and suppression of ubiquitin-proteasome system (UPS) function. The curcumin-reduced Akt expression, cell proliferation, and migration were prevented by genetic and pharmacological inhibition of autophagy but not by UPS inhibition. Additionally, inactivation of AMPK by its specific inhibitor compound C or by target shRNA-mediated silencing attenuated curcumin-activated autophagy. Thus, these results indicate that curcumin-stimulated AMPK activity induces activation of the autophagy-lysosomal protein degradation pathway leading to Akt degradation and the subsequent suppression of proliferation and migration in breast cancer cell.

Our classification of the anatomic variations of the cystic artery will be useful for decreasing uncontrollable cystic artery hemorrhage, and avoiding extrahepatic bile duct injury.

Objective: To determine the role of laparoscopy in diagnosis and surgical treatment of perforated Meckel's diverticulum (MD) in adults.Methods: Between July 2003 and July 2011, fifteen patients were seen with perforated MD. Eleven were male and four were female. The median age was 38 years (range, 21-68). All patients presented with a sudden onset of pain. Among them 9 had a past medical history of bloody stools and /or chronic recurrent abdominal pain. 2 were preoperatively diagnosed with perforated MD confirmly and 4 suspiciously, 9 with perforated acute appendicitis. All 15 patients underwent exploratory laparoscopy.Results: 4 patients with broad-base(≧ 2 cm) and 2 patients with narrow-base(<2 cm) whose perforative site was near the base underwent laparoscopically assisted extracorporal bowel segment resection, the other 9 patients with narrow-base(<2 cm) underwent laparoscopically intraabdominal wedge resection of the MD. No intraoperative or postoperative complications occurred. The median hospital stay was 4 days (range, 2-7days). The histopathologic studies showed heterotopic gastric mucosa (HGM) in 10 cases (66.7%). All patients recovered uneventfully.Conclusion: To patients with sudden abdomen pain mimic acute appendicitis accompanied by a past medical history of bloody stools and/or chronic recurrent abdominal pain, proferated MD should be kept in mind as a differential diagnosis. Laparoscopy is a safe and effective surgical modality for diagnosis of proferated MD and has a therapeutic role that results in an excellent cosmetic result.

Hepatocellular carcinoma (HCC) is a serious threat to human health. HCC is a malignant tumor and its invasion and metastasis are the result of multigene interactions. Matrix metalloproteinase-2 (MMP-2) is capable of degrading the majority of components of the extracellular matrix and is regarded to closely correlate with tumor invasion and metastasis. Furthermore, the hypoxia-inducible factor 1α (HIF-1α) is an important transcription factor, which is closely associated with the process of tumor growth. The aim of the present study was to investigate the expression of MMP2 and HIF-1α) in HCC, and the relationship between MMP2/HIF-1α protein expression and the clinical/pathological characteristics of HCC. The mRNA levels of MMP2 and HIF-1α were detected in 32 cases of HCC and the corresponding normal adjacent tissues with fluorescence-based quantitative polymerase chain reaction (qPCR). The protein expression of MMP2 and HIF-1α was assessed in 45 HCC cases and 33 cases of corresponding normal adjacent tissue, using immunohistochemical methods. The association between MMP2/HIF-1α and pathological features of HCC, and the correlation between MMP2 and HIF-1α were analyzed. The Kaplan-Meier method was used to assess the impact of MMP2 and HIF-1α expression on survival. The fluorescence-based qPCR demonstrated that MMP2 and HIF-1α mRNA expression levels in the HCC tissues were 0.84±0.17 and 0.87±0.11, respectively, which were significantly higher than those in the adjacent normal tissues (0.70±0.13 and 0.68±0.13, respectively; P<0.05). Immunohistochemical analysis revealed that MMP2 and HIF-1α protein expression in the HCC tissues was 63.1 and 70.8%, respectively, which was also higher than that in the adjacent normal tissues (34.2 and 36.8%, respectively). There was no significant correlation between the expression of MMP2 or HIF-1α protein and the age or gender of patients with HCC (P>0.05). However, there was significant correlation between MMP2 or HIF-1α protein expression and tumor size, metastasis, presence of a capsule and clinical TNM staging of HCC. Their expression also had a significant effect on patient survival time. In conclusion, MMP2 and HIF-1α are overexpressed in HCC, and the MMP2 signaling pathway may promote the development of HCC together with HIF-1α.