TLR2 is expressed in human articular cartilage and is upregulated by proarthritic agents including IL-1beta and fibronectin fragments. Signaling through TLR is a novel pro-inflammatory mechanism in osteoarthritis and targeting of these signaling pathways may be of value in treatment of degenerative joint disease.

Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive phenotype. Gα12 gep oncogene product couples to G-protein-coupled receptors, whose ligand levels are frequently increased in tumor microenvironments. Here, we report Gα12 overexpression in human HCC and the resultant induction of zinc-finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation. Gα12 expression was higher in HCC than surrounding non-tumorous tissue. Transfection of Huh7 cell with an activated mutant of Gα12 (Gα12QL) deregulated microRNA (miRNA or miR)-200b/a/429, -194-2/192 and -194-1/215 clusters in the miRNome. cDNA microarray analyses disclosed the targets affected by Gα12 gene knockout. An integrative network of miRNAs and mRNA changes enabled us to predict ZEB1 as a key molecule governed by Gα12. Decreases of miR-200a/b, -192 and -215 by Gα12 caused ZEB1 induction. The ability of Gα12 to decrease p53 levels, as a result of activating protein-1 (AP-1)/c-Jun-mediated mouse double minute 2 homolog induction, contributed to transcriptional deregulation of the miRNAs. Gα12QL induced ZEB1 and other epithelial-mesenchymal transition markers with fibroblastoid phenotype change. Consistently, transfection with miR-200b, -192 or -215 mimic prevented the ability of Gα12QL to increase tumor cell migration/invasion. In xenograft studies, sustained knockdown of Gα12 decreased the overall growth rate and average volume of tumors derived from SK-Hep1 cell (mesenchymal-typed). In HCC patients, miR-192, -215 and/or -200a were deregulated with microvascular invasion or growth advantage. In the HCC samples with higher Gα12 level, a correlation existed in the comparison of relative changes of Gα12 and ZEB1. In conclusion, Gα12 overexpressed in HCC causes ZEB1 induction by deregulating p53-responsive miRNAs, which may facilitate epithelial-mesenchymal transition and growth of liver tumor. These findings highlight the significance of Gα12 upregulation in liver tumor progression, implicating Gα12 as an attractive therapeutic target.

The clinical outcomes of malunited scaphoids after reconstruction for scaphoid fractures nonunion did not differ significantly from well-united scaphoids at a minimum 5-year follow-up.

We generated RAPD, SCAR, and conserved 18S rDNA markers for classifying and identifying cultivars of Pyrus pyrifolia (Japanese pear) and P. communis (European pear). PCR amplification with selected specific primers-LCH327UP and LCH327DOWN-was performed using DNA extracted from 25 P. pyrifolia and P. communis cultivars. The 1,380-bp fragment was amplified from P. communis cvs. Beurre Giffard, Cascade, Conference, Clapp's Favorite, Packhams Triumph, and Winter Nelis. RAPD has only a dominant single band of 1,380-bp, however, SCAR has one or more band of the same size. Amplification involving sequence-specific primer pairs LCH346UP and LCH346DOWN resulted in a loss of polymorphism. The 1,190-bp fragment was amplified from all P. pyrifolia cultivars. The conserved sequences of the 18S rDNA fragment of 25 pear cultivars were amplified and analyzed with 42 restriction enzymes. Compared with P. pyrifolia cultivars, they lacked the restriction enzyme site of KpnI and had one less RsaI site. Cultivar Gamcheonbae had a specific PstI restriction site, while cvs. Mansoo and Conference pear digested with AluI showed a different presentation than other cultivars. For the Okusankichi and Shinil pears TaqI was best marker for identification in P. pyrifolia. These results can be adopted for identifying pear cultivars; to date there is no standard marker for identifying the cultivars of fruit trees in Korean fruit tree breeding programs.