A growing body of evidence suggests that nobiletin (5,6,7,8,3,4-hexamethoxy flavone) from the peel of citrus fruits, enhances the damaged cognitive function in disease animal models. However, the neuroprotective mechanism has not been clearly elucidated. Since nobiletin has shown anti-inflammatory effects in several tissues, we investigated whether nobiletin suppresses excessive microglial activation implicated in neurotoxicity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cell culture models. Release of nitric oxide (NO), the major inflammatory mediator in microglia, was markedly suppressed in a dose-dependent manner following nobiletin treatment (1-50 mM) in LPS-stimulated BV-2 microglia cells. The inhibitory effect of nobiletin was similar to that of minocycline, a well-known microglial inactivator. Nobiletin significantly inhibited the release of the proinflammatory cytokine tumor necrosis factor (TNF-a) and interleukin-1b (IL-1b). LPS-induced phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun NH 2 -terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) were also significantly inhibited by nobiletin treatment. In addition, nobiletin markedly inhibited the LPS-induced pro-inflammatory transcription factor nuclear factor kB (NF-kB) signaling pathway by suppressing nuclear NF-kB translocation from the cytoplasm and subsequent expression of NF-kB in the nucleus. Taken together, these results may contribute to further exploration of the therapeutic potential and molecular mechanism of nobiletin in relation to neuroinflammation and neurodegenerative diseases.

No abstract

Gastric lipomatosis is an extremely rare condition. We present a case of a 69-year-old woman admitted with epigastric soreness. Computerized tomography (CT) revealed extrinsically compressing, fat-containing mass lesions on the entire gastric wall of the antrum and body except for the lesser curvature. A subtotal gastrectomy was performed. Pathology findings confirmed a gastric lipomatosis with multiple gastric ulcerations and extensive disruptions of the muscular layers. This case and reports of other gastric lipomatosis cases indicate that CT should be used to characterize large submucosal masses because CT can show the specific nature and extent of the disease. We believe that surgical treatment is the most appropriate treatment for symptomatic gastric lipomatosis that shows extensive gastric involvement, or when there are multiple gastric lipomas.

Abstract. Reduced glutathione (GSH) is an abundant tripeptide present in the majority of cell types.

No abstract

Here, we investigated whether over-activation of AKT pathway is important in the resistance to 5-fluorouracil (5-FU) in SNU-C5/5-FU cells, 5-FU-resistant human colon cancer cells. When compared to wild type SNU-C5 cells (WT), SNU-C5/5-FU cells showed over-activation of PI3K/AKT pathway, like increased phosphorylation of AKT, mTOR, and GSK-3β, nuclear localization of β-catenin, and decreased E-cadherin. Moreover, E-cadherin level was down-regulated in recurrent colon cancer tissues compared to primary colon cancer tissues. Gene silencing of AKT1 or treatment of LY294002 (PI3 kinase inhibitor) increased E-cadherin, whereas decreased phospho-GSK-3β. LY294002 also reduced protein level of β-catenin with no influence on mRNA level. PTEN level was higher in SNU-C5/WT than SNU-C5/5-FU cells, whereas the loss of PETN in SNU-C5/WT cells induced characteristics of SNU-C5/5-FU cells. In SNU-C5/5-FU cells, NF-κB signaling was activated, along with the overexpression of COX-2 and stabilization of survivin. However, increased COX-2 contributed to the stabilization of survivin, which directly interacts with cytoplasmic procaspase-3, while the inhibition of AKT reduced this cascade. We finally confirmed that combination treatment with 5-FU and LY294002 or Vioxx could induce apoptosis in SNU-C5/5-FU cells. These data suggest that inhibition of AKT activation may overcome 5-FU-resistance in SNU-C5/5-FU cells. These findings provide evidence that over-activation of AKT is crucial for the acquisition of resistance to anticancer drugs and AKT pathway could be a therapeutic target for cancer treatment.

PurposeClinical stage of gastric cancer is currently assessed by computed tomography. Accurate clinical staging is important for the tailoring of therapy. This study evaluated the accuracy of clinical N staging using stomach protocol computed tomography.Materials and MethodsBetween March 2004 and November 2012, 171 patients with gastric cancer underwent preoperative stomach protocol computed tomography (Jeju National University Hospital; Jeju, Korea). Their demographic and clinical characteristics were reviewed retrospectively. Two radiologists evaluated cN staging using axial and coronal computed tomography images, and cN stage was matched with pathologic results. The diagnostic accuracy of stomach protocol computed tomography for clinical N staging and clinical characteristics associated with diagnostic accuracy were evaluated.ResultsThe overall accuracy of stomach protocol computed tomography for cN staging was 63.2%. Computed tomography images of slice thickness 3.0 mm had a sensitivity of 60.0%; a specificity of 89.6%; an accuracy of 78.4%; and a positive predictive value of 78.0% in detecting lymph node metastases. Underestimation of cN stage was associated with larger tumor size (P<0.001), undifferentiated type (P=0.003), diffuse type (P=0.020), more advanced pathologic stage (P<0.001), and larger numbers of harvested and metastatic lymph nodes (P<0.001 each). Tumor differentiation was an independent factor affecting underestimation by computed tomography (P=0.045).ConclusionsComputed tomography with a size criterion of 8 mm is highly specific but relatively insensitive in detecting nodal metastases. Physicians should keep in mind that computed tomography may not be an appropriate tool to detect nodal metastases for choosing appropriate treatment.

Intestinal duplications are rare congenital anomalies that can occur anywhere in the gastrointestinal tract. They are most commonly located in the ileum and are usually detected in infancy or early childhood. Duplicated segments are usually firmly attached to and sometimes communicate with the normal gastrointestinal tract. Rarely, intestinal duplications are completely isolated, thus not associated at all with any part of the gastrointestinal tract. Such duplications do not share a common blood supply with the adjacent normal intestinal segment, unlike the usual form of duplication, but rather have a separate vascular pedicle. Reports of completely isolated duplication cysts in adults are extremely rare; we found only five such reports in the English-language medical literature. Here, we report a case of a completely isolated duplication cyst 12 cm long in an adult female. The cyst had no connection to any part of the intestinal tract and had a dedicated vascular pedicle.