Sirolimus as a promising drug therapy for blue rubber bleb nevus syndrome: Two-case report.

Blue rubber bleb nevus syndrome is a very rare systemic vascular malformation frequently affecting the skin and the gastrointestinal tract. The pathogenesis of the disease is still unclear, and the standard treatment does not exist. This study reports two blue rubber bleb nevus syndrome cases, of which the second patient received the TEK gene mutations detection and got a low-dose sirolimus therapy, compared with the first patient who was not treated with sirolimus. The report shows some positive findings of TEK gene mutations and the efficacy of sirolimus treatment. We postulate that the TEK gene mutations play an important role in the pathogenesis. The mutations of different locations of the TEK gene cause a wide range of activating TIE2 mutations, which could stimulate the mammalian target of rapamycin signaling pathways to mediate angiogenesis, resulting in different clinical phenotypes of cutaneomucosal venous malformations. Sirolimus could effectively block the upstream and downstream factors of mammalian target of rapamycin signaling pathways to achieve the antiangiogenic effect. The initial dose of sirolimus can be 0.05-0.1 mg/kg/d for a trough level of 5-15 µg/L in the treatment of blue rubber bleb nevus syndrome. However, a lower-dose sirolimus is also effective while minimizing the side effects.

Development of Cre-loxP technology in zebrafish to study the regulation of fish reproduction.

One cannot seek permission to market transgenic fish mainly because there is no field test or any basic research on technological developments for evaluating their biosafety. Infertility is a necessary adjunct to exploiting transgenic fish unless completely secure land-locked facilities are available. In this study, we report the generation of a Cre transgenic zebrafish line using a cytomegalovirus promoter. We also produced fish carrying the Bax1 and Bax2 plasmids; these genes were separated by two loxP sites under a zona pellucida C promoter or were driven by an anti-Müllerian hormone promoter. We inserted a red fluorescent protein gene between the two loxP sites. After obtaining transgenic lines with the two transgenic fish crossed with each other (Cre transgenic zebrafish x loxP transgenic zebrafish), the floxed DNA was found to be specifically eliminated from the female or male zebrafish, and apoptosis gene expressions caused ovarian and testicular growth cessation and degeneration. Overexpression of the Bax1 and Bax2 genes caused various expression levels of apoptosis-related genes. Accordingly, this transgenic zebrafish model system provides a method to produce infertile fish and may be useful for application to genetically modified fish.

Piscidin-1, an antimicrobial peptide from fish (hybrid striped bass morone saxatilis x M. chrysops), induces apoptotic and necrotic activity in HT1080 cells.

Piscidin-1, a 22-residue cationic peptide isolated from mast cells of a hybrid striped bass, has potent antimicrobial activities against both gram-positive and -negative bacteria. To date, there is no report of its antitumor activity on any tumor cell lines. In this study, we examined the antitumor activity of a synthetic piscidin-1 peptide against several human cancer cell lines using an MTS assay and soft-agar colony-formation assay. We found that a low dose of piscidin induces both apoptosis and necrosis in HT1080 cells, as shown by annexin-V/propidium iodide and acridine orange/ethidium bromide staining, and triggers a necrotic cell death pathway in a short period with high-dose treatment. The destruction of cell membranes by piscidin-1 was demonstrated by transmission electron microscopy. Furthermore, piscidin-1 also inhibits the migration of HT1080 cells in a dose-dependent manner. This study provides the first evidence of the anticancer activity of the antimicrobial peptide, piscidin-1, with potential implications for the treatment of cancer.

Optical panel with full multitouch using patterned indium tin oxide.

This study proposes an optical panel with full multitouch using the patterned indium tin oxide (ITO) and an algorithm matrix to avoid ghost points. The patterned ITOs include the virtual high and low impedances. The algorithm matrix with two configurations of equivalent circuits for array scanning is derived using the voltage divider rule. The fabrication process of the multitouch panel is carried out using microelectromechanical systems technology. The optical characteristics of the multitouch panel in the UV, visible, and IR regions are measured using photometric analysis. The multitouch panel, containing sensing pixels of 30×30 arrays, has a pixel size of 2×2 mm2 and a pitch distance of 2 mm. The average values of high and low impedances are 53.23 and 9.3 k Ω, respectively. The maximum transmittance is about 74.2% at the wavelength of 692 nm. The multitouch panel based on high and low impedance patterns has been specifically designed to offer good adjacent touch resolution and sensitivity for reality multitouch applications. In addition, the patterned design and the algorithm matrix provide unlimited multitouch points and avoid ghost points.

The S subunit of D-ornithine aminomutase from Clostridium sticklandii is responsible for the allosteric regulation in D-alpha-lysine aminomutase.

Ornithine and lysine are degraded in quite a similar way in Clostridium sticklandii. Both pathways involve adenosylcobalamin-dependent enzymes, d-ornithine 4,5-aminomutase and lysine 5,6-aminomutase. According to previous reports, lysine 5,6-aminomutase is an ATP-dependent allosteric enzyme with many different activators and inhibitors. However, recent studies indicate that ATP does not have a regulatory effect on the recombinant enzyme. To monitor the activity of lysine aminomutase, a novel capillary electrophoresis-based assay method was developed. The present results demonstrate that the S subunit of d-ornithine aminomutase, OraS, is capable of forming a complex with KamDE of lysine 5,6-aminomutase and restores the enzyme's ATP-dependent allosteric regulation. Not only does ATP lower the K(m) of the KamDE-OraS complex for adenosylcobalamin and pyridoxal phosphate, but also OraS protein alone lowers the K(m) of KamDE for adenosylcobalamin and pyridoxal phosphate. The activity of reconstituted enzyme can also be activated by ammonium ion as reported by Morley and Stadtman.

Hydrolysis, lactonization, and identification of alpha(2 --> 8)/alpha(2 --> 9) alternatively linked tri-, tetra-, and polysialic acids.

Alpha-(2 --> 8)/alpha(2 --> 9) alternatively linked polysialic acid (PSA) can be identified by controlled hydrolysis followed by the analysis with capillary electrophoresis (CE). Due to the different stability of alpha(2 --> 8) and alpha(2 --> 9) linkages in acidic hydrolysis, oligosialic acids (OSAs) from the hydrolysis of alpha(2 --> 8)/alpha(2 --> 9) OSA/PSA could be classified into two groups in the CE profile. The group with an odd numerical degree of polymerization (DP) had two peaks in the CE profile, and the other group, with even number of DP, showed one peak. Each alternating alpha(2 --> 8)/alpha(2 --> 9) linked OSA contains two isomers: one starts with the alpha(2 --> 8) linkage from the nonreducing end and the other starts with the alpha(2 --> 9) linkage from the nonreducing end. Trimers and tetramers were isolated by using a Mono Q column with an HPLC system. The two trimer isomers are alpha(2 --> 8)/alpha(2 --> 9) and alpha(2 --> 9)/alpha(2 --> 8) linkages and only showed partial separation by CE. After lactonization, sialidase hydrolysis, and alkaline treatment, the two trimer isomers could be separated and identified by CE analysis, but only the alpha(2 --> 8)/alpha(2 --> 9) trimer could be converted to the dilactone in glacial acetic acid. The two tetramer isomers could be converted to four monolactones and three dilactones. These lactonized species could be identified on the basis of several principles in sialidase hydrolysis and lactonization. In conclusion, regioselectivity on the lactonization of oligosialic acids proceeds under several principles: (1) Lactonization takes place more easily in the alpha(2 --> 8) linkage than in the alpha(2 --> 9) linkage; (2) all of the positions of alpha(2 --> 8) linkages in alpha(2 --> 8)/alpha(2 --> 9) alternatively linked OSA can be lactonized regardless of external or internal carboxyl groups involved; and (3) for the site of alpha(2 --> 9) linkage, only internal carboxyl groups can be lactonized.