TPPU protects tau from HO-induced hyperphosphorylation in HEK293/tau cells by regulating PI3K/AKT/GSK-3β pathway / 华中科技大学学报（医学）（英德文版）

Neurofibrillary pathology of abnormally hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) and other tauopathies. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway is pivotal for tau phosphorylation. Inhibition of soluble epoxide hydrolase (sEH) metabolism has been shown to effectively increase the accumulation of epoxyeicosatrienoic acids (EETs), which are cytochrome P450 metabolites of arachidonic acid and have been demonstrated to have neuroprotective effects. However, little is known about the role of sEH in tau phosphorylation. The present study investigated the role of a sEH inhibitor, 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl] urea (TPPU), on HO-induced tau phosphorylation and the underlying signaling pathway in human embryonic kidney 293 (HEK293)/Tau cells. We found that the cell viability was increased after TPPU treatment compared to control in oxidative stress. Western blotting and immunofluorescence results showed that the levels of phosphorylated tau at Thr231 and Ser396 sites were increased in HO-treated cells but dropped to normal levels after TPPU administration. HOinduced an obvious decreased phosphorylation of GSK-3β at Ser9, an inactive form of GSK-3β, while there were no changes of phosphorylation of GSK-3β at Tyr216. TPPU pretreatment maintained GSK-3β Ser 9 phosphorylation. Moreover, Western blotting results showed that TPPU upregulated the expression of p-Akt. The protective effects of TPPU were found to be inhibited by wortmannin (WT, a specific PI3K inhibitor). In conclusion, these results suggested that the protective effect of TPPU on HO-induced oxidative stress is associated with PI3K/Akt/GSK-3β pathway.

Comparative genomic hybridization: the profile of chromosomal imbalances in rhabdomyosarcoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To characterize the profile of chromosomal imbalances of rhabdomyosarcoma(RMS).</p><p><b>METHODS</b>Comparative genomic hybridization (CGH) was used to investigate genomic imbalances in 25 cases of primary RMS including 10 cases of alveolar rhabdomyosarcoma (ARM), 12 cases of embryonic rhabdomyosarcoma (ERMS), 3 cases of polymorphic rhabdomyosarcoma (PRMS) and 2 RMS cell lines (A240 originated from ARMS and RD from PRMS), with correlation to histological type, pathologic grading, clinical staging, gender and age, respectively.</p><p><b>RESULTS</b>All twenty-five rhabdomyosarcomas showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. (1) The frequently gained chromosome regions in RMS were 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q, and the frequently lost chromosome regions were 3p, 11p, 6p. (2) The frequently gained chromosome arms in ARMS were 12q, 2p, 6, 2q, 4q, 10q, 15q. The frequently lost chromosome arms were 3p, 6p, 1q, 5q. The frequently gained chromosome regions in ERMS were 7p, 9q, 2p, 18q, 1p, 8q. The frequently lost chromosome arms in ERMS were 11p. (3) The frequently gained chromosome arms in translocation associated RMS were 12q, 2, 6, 10q, 4q and 15q (> 30%), 3p, 6p, 5q (> 30%) were the frequently loss chromosome arms. The frequently gained chromosome regions in non-translocation associated RMS were 2p, 9q, 18q (> 30%), and 11p, 14q (> 30%) were the frequently loss chromosome regions. Gain of 12q was significantly correlated with the translocation-associated tumors (P < 0.05). (4) Gains of 9q was significantly correlated with clinical staging (P < 0.05).</p><p><b>CONCLUSIONS</b>Gain of 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q and loss of 3p, 11p, 6p may be involved in the tumorigenesis of RMS. Gains of 12q may be correlated with gene fusion/chromosomal translocation in ARMS. Gains of 9q may be correlated with an early tumor stage of RMS.</p>