Insulin and insulin growth factor have central roles in growth, metabolism and ageing of animals, including Drosophila melanogaster. In Drosophila, insulin-like peptides (Dilps) are produced by specialized neurons in the brain. Here we show that Drosophila short neuropeptide F (sNPF), an orthologue of mammalian neuropeptide Y (NPY), and sNPF receptor sNPFR1 regulate expression of Dilps. Body size was increased by overexpression of sNPF or sNPFR1. The fat body of sNPF mutant Drosophila had downregulated Akt, nuclear localized FOXO, upregulated translational inhibitor 4E-BP and reduced cell size. Circulating levels of glucose were elevated and lifespan was also extended in sNPF mutants. We show that these effects are mediated through activation of extracellular signal-related kinases (ERK) in insulin-producing cells of larvae and adults. Insulin expression was also increased in an ERK-dependent manner in cultured Drosophila central nervous system (CNS) cells and in rat pancreatic cells treated with sNPF or NPY peptide, respectively. Drosophila sNPF and the evolutionarily conserved mammalian NPY seem to regulate ERK-mediated insulin expression and thus to systemically modulate growth, metabolism and lifespan.

a b s t r a c tMethionine sulfoxide reductase A (msrA) was previously found to increase resistance to oxidative stress and longevity in animals. We identified Drosophila msrA (dmsrA), a Drosophila homolog of human msrA, as a downstream effector of forkhead box O (FOXO) signaling in Drosophila, which enhances resistance to oxidative stress and increases survival under stressed conditions. Additionally, overexpression of dmsrA in neurons extended the lifespan of flies. Moreover, overexpression of dmsrA in fat body cells caused FOXO to translocate to the nucleus, implying that this possible positive feedback loop between dmsrA and FOXO could potentiate the antioxidant activity of dmsrA and increase the lifespan in Drosophila.

The aim of this study was to evaluate MR imaging findings of the associated findings in surrounding tissues of the extra-articular soft tissue ganglion cysts around the knee. We retrospectively reviewed MR images of 30 patients who had surgically confirmed extra-articular soft tissue ganglion cysts around the knee with focus on the associated findings in surrounding tissues, such as muscle, subcutaneous fat, bone, and nerve. The most common associated finding was the visualization of channel between ganglion cyst and the joint, which was demonstrated in 20 cases (continuous type in 12 cases and discontinuous type in 8 cases). Other associated findings were seen in 15 cases; pericystic edema ( n=9), bony remodelling ( n=3), and nerve involvement ( n=3). The bony remodelling involved the proximal metaphysis of tibia in all 3 cases. Two patients with nerve involvement had deep peroneal nerve in subacute phase and one involved common peroneal nerve in chronic phase. The MR imaging is a useful imaging modality to evaluate the associated findings in extra-articular soft tissue ganglion cysts around the knee. The evaluation of these associated findings is helpful for the differentiation of ganglion cysts from other cystic lesions around the knee.

A citrus extract containing flavonoids and ascorbic acid was used as a supplement to investigate its effect on lipids in hypercholesterolemic hamsters. Ascorbic acid or the flavonoids were without effect except that ascorbate did significantly raise HDL. After 1 month of feeding, the citrus extract plus ascorbic acid synergistically caused a significant reduction of 77%, 66%, and 40% in plasma total cholesterol, LDL + VLDL, and triglycerides, respectively, in comparison to the control group. The extract was also a synergistic inhibitor of in vitro cupric ion LDL + VLDL oxidation compared with ascorbic acid or the flavonoids alone. In a second 10-week hamster study, citrus extract plus ascorbate also significantly lowered plasma lipids, lipid peroxides, and ex vivo LDL + VLDL oxidizability vs a control group. Citrus extract plus ascorbate strongly inhibited atherosclerosis, and there was a significant correlation between several indices of oxidative susceptibility and atherosclerosis. Keywords: Lipids; atherosclerosis; flavonoids; lipid peroxidation; hamster

Salmonella enterica serovar Typhimurium (hereafter referred to as Salmonella), a virulent pathogen, is known to induce host-cell death. Using reverse transcription-quantitative polymerase chain reaction, a 28-fold increase of microRNA (miR)-155 expression in RAW 264.7 macrophages was observed following infection with Salmonella for 24 h. This miR-155 upregulation increased macrophage cell death by up to 40% in 48 h following infection. Western blot analysis revealed that receptor interacting protein 1 (RIP1) and 3 (RIP3) were increased at 18 h following miR-155 transfection to macrophages, similar to Salmonella infection. In addition, inhibition of RIP1 by pre-incubating macrophages with necrostatin-1, a RIP1 specific inhibitor, increased the viability of Salmonella-infected cells and miR-155-transfected cells by up to 20%. The cleavage of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) was also enhanced by miR-155 induction upon Salmonella infection. Therefore, it was suggested that RIP1/3-induced necroptosis and PARP-1-mediated necrosis caused by miR-155 induction may represent distinct routes of programmed necrotic cell death of Salmonella-infected macrophages.

Excess scarring of the conjunctiva after glaucoma filtration surgery is a major cause of failure. Transforming growth factor (TGF)-β is critically involved in post-operative scarring. Lithium inhibits TGF-β-induced gene protein expression in corneal fibroblasts and inhibits TGF-β-induced epithelial mesenchymal transition. Here, we investigated the effects of LiCl on TGF-β1-mediated signaling pathways and on myofibroblast transdifferentiation of human Tenon's capsule fibroblasts (HTFs). LiCl treatment reduced expression of TGF-β1-induced α-SMA expression in HTFs. LiCl also decreased Akt phosphorylation induced by TGF-β1. TGF-β1-induced α-SMA expression was significantly decreased by LY294002 and Akt siRNA indicating that these changes are mediated by the PI3K/Akt pathway. Thus, LiCl induces the suppression of transdifferentiation stimulated by TGF-β1 by the regulation of PI3K/Akt signaling in HTFs.

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The Tat-PTEN fusion proteins were successfully transduced into the SCF cells and induced the suppression of transdifferentiation and fibrosis through the regulation of TGF-β-mediated signaling. The ability of the Tat-PTEN fusion protein to regulate cell survival could potentially be applied to protein therapy to counteract postoperative scarring in glaucoma surgery.