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Aims: Neurodegenerative diseases are the leading cause of morbidity and mortality worldwide. Several studies have shown that tetramethylpyrazine (TMP) is an effective therapy for neurodegenerative diseases and that it acts by inhibiting the activation of microglial cells in response to inflammatory stimuli. However, the molecular mechanisms underlying the action of TMP remain unknown., Main Methods: Proteomic analysis was used to generate novel insights into the mechanism by which TMP inhibits microglial activation, and western blotting was used to validate candidate proteins., Key Findings: To identify candidate proteins affected by TMP in lipopolysaccharide-activated microglia, we performed proteomic analysis using iTRAQ labelling coupled with LC TRIPLE-TOF, and we identified 5187 unique proteins. Among these, 266 proteins were differentially expressed and considered putative candidate proteins. Protein annotation revealed that the differentially expressed proteins, such as inducible nitric oxide synthase (iNOS) and ERO1-like protein (ERO1L), might be involved in reducing cellular oxidation in response to stress. Ingenuity pathway analysis revealed that the differentially expressed proteins were involved in a variety of signalling pathways, including liver X receptor/retinoid X receptor (LXR/RXR) activation and the production of nitric oxide and reactive oxygen species in macrophages. Furthermore, one of the differentially expressed protein candidates detected by iTRAQ, iNOS, was confirmed by western blotting., Significance: Our data suggest that iTRAQ technology is an effective tool to study the mechanism by which TMP inhibits activated microglia. TMP decreased the expression of LXR/RXR-mediated iNOS, which reduced microglial activation in response to inflammatory stimuli., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) cells are insensitive to BCR-ABL tyrosine kinase inhibitor imatinib, the underlying mechanisms remain largely unknown. Here, we showed that imatinib treatment induced significant upregulation of miR-21 and downregulation of PTEN in Ph+ ALL cell line Sup-b15. Transient inhibition of miR-21 resulted in increased apoptosis, PTEN upregulation and AKT dephosphorylation, whereas ectopic overexpression of miR-21 further conferred imatinib resistance. Furthermore, knockdown of PTEN protected the cells from imatinib-induced apoptosis achieved by inhibition of miR-21. Additionally, PI3K inhibitors also notably enhanced the effects of imatinib on Sup-b15 cells and primary Ph+ ALL cells similar to miR-21 inhibitor. Therefore, miR-21 contributes to imatinib resistance in Ph+ ALL cells and antagonizing miR-21 demonstrates therapeutic potential by sensitizing the malignancy to imatinib therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The maternal effect of different Se source in offspring of young broiler breeders has been reported, but the lasting maternal effect of different sources of Se on offspring of breeders has received limited attention, so this study was conducted to investigate the effects of different maternal Se sources on Se retention, antioxidant status, and meat quality of 56-d-old offspring of broiler breeders. A total of two hundred forty 39-wk-old Lingnan Yellow broiler breeders were randomly distributed into 2 treatments, each of which was replicated 3 times with 40 birds per replicate, with a 14-d pretreatment and 56-d trial period. The treatments were fed a basal corn-soybean diet (0.04 mg∙kg⁻¹ Se) supplemented with 0.3 mg∙kg⁻¹ sodium selenite (SS) or selenomethionine (Se-Met). Fertile eggs were collected for incubation, after which 180 healthy chicks from each treatment were selected and randomly allocated into 3 replicates, with 60 birds per replicate. All the chicks were fed the same basal diet (0.04 mg∙kg⁻¹ Se) for 56 d. The Se concentrations in serum and tissues (liver, kidney, and breast muscle) of the 56-d-old offspring were significantly (P < 0.01) increased by maternal Se-Met intake compared with maternal SS intake. The antioxidant status of the 56-d-old offspring was greatly improved by maternal Se-Met supplementation in contrast with maternal SS supplementation, which was shown by increased glutathione peroxidase activity in serum and breast muscle (P < 0.01), glutathione concentration in serum (P < 0.05), and total antioxidant capability in pancreas (P < 0.01), as well as cytosolic glutathione peroxidase mRNA abundance in breast muscle, liver (P < 0.01), and pancreas (P < 0.05). The maternal Se-Met treatment was more effective in maintaining the shape of liver and pancreas cells, cell nuclei, chromatin, as well as cell membrane structure, and more organelles were observed in liver cells. The maternal Se-Met treatment had significant (P < 0.05) reduced the 48-h drip loss of 56-d-old offspring in comparison with maternal SS treatment. The results suggest that maternal Se-Met diet is superior to maternal SS diet in increasing Se retention and improving antioxidant status and meat quality of 56-d-old offspring., (© 2014 Poultry Science Association Inc.)

Aim: The aim of this study is to explore the underlying molecular mechanism of curcumin-induced apoptosis in human hepatocellular carcinoma (HCC) Huh7 cells., Main Methods: Fas and FasL mRNA expression was analyzed by reverse transcription PCR. Western blot was applied to detect the protein expression of Bcl-2 family members, MAPK family members, c-Jun, c-Fos, ATF-2, caspase-3, PARP, TNF receptor family members and the respective ligands. Apoptotic cells were assayed with annexin V/PI double staining and flow cytometry., Key Findings: Curcumin treatment resulted in a fast and significant increase of Fas and Fas ligand (FasL) along with activation of caspase-3 and cleavage of PARP in Huh7 cells. Inhibition of caspase-3 activity by the specific inhibitor Z-DEVD-FMK rescued Huh7 cells from curcumin-induced apoptosis. Neutralization of FasL significantly protected the cells from curcumin-induced caspase-3 activation and apoptosis in a dose-dependent manner. Moreover, p38 was rapidly activated in response to curcumin, and inactivation of p38 by pharmacologic inhibitor SB203580 dramatically suppressed curcumin-induced FasL expression and apoptosis., Significance: Our results demonstrated that curcumin induces apoptosis through p38-denpendent up-regulation of FasL in Huh7 cells., (Copyright © 2012 Elsevier Inc. All rights reserved.)