The algal selenoproteomes.

BACKGROUND: Selenium is an essential trace element, and selenocysteine (Sec, U) is its predominant form in vivo. Proteins that contain Sec are selenoproteins, whose special structural features include not only the TGA codon encoding Sec but also the SECIS element in mRNA and the conservation of the Sec-flanking region. These unique features have led to the development of a series of bioinformatics methods to predict and research selenoprotein genes. There have been some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, has been very limited. RESULTS: In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to record these algae selenoprotein genes ( www.selenoprotein.com ). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families. CONCLUSIONS: This study reveals the primordial state of the eukaryotic selenoproteome. It is an important clue to explore the significance of selenium for primordial eukaryotes and to determine the complete evolutionary spectrum of selenoproteins in all life forms.

Synergism of wt-p53 and synthetic material in local nano-TAE gene therapy of hepatoma: comparison of four systems and the possible mechanism.

BACKGROUND: TAE-gene therapy for hepatoma, incorporating the tumor-targeted therapeutic efficacy of trans-arterial embolization, hydroxyapatite nanoparticles (nHAP) and anti-cancer wild-type p53 gene (wt-p53), was presented in our former studies (Int J Nanomedicine 8:3757-68, 2013, Liver Int 32:998-1007, 2012). However, the incompletely antitumoral effect entails defined guidelines on searching properer materials for this novel therapy. METHODS: Unmodified nHAP, Ca(2+) modified nHAP, poly-lysine modified nHAP and liposome were separately used to form U-nanoplex, Ca-nanoplex, Pll-nanoplex, L-nanoplex respectively with wt-p53 expressing plasmid. The four nanoplexs were then applied in vitro for human normal hepacyte L02 and hepatoma HePG2 cell line, and in vivo for rabbits with hepatic VX2 tumor by injection of nanoplexs/lipiodol emulsion into the hepatic artery in a tumor target manner. The distribution, superficial potential, physical structure, morphology and chemical compositions of nanoplexs were evaluated by TEM, SEM, EDS etc., with the objective of understanding their roles in hepatoma TAE-gene therapy. RESULTS: In vitro, L-nanoplex managed the highest gene transferring efficiency. Though with the second highest transfection activity, Pll-nanoplex showed the strongest tumor inhibition activity while maintaining safe to the normal hepacyte L02. In fact, only Pll-nanoplex can combine both the antitumoral effect to HePG2 and safe procedure to L02 among the four systems above. In vivo, being the only one with successful gene transference to hepatic VX2 tumor, Pll-nanoplex/lipiodol emulsion can target the tumor more specifically, which may explain its best therapeutic effect and hepatic biologic response. Further physical characterizations of the four nanoplexs suggested particle size and proper electronic organic surface may be crucial for nano-TAE gene therapy. CONCLUSION: Pll-nanoplex is the most proper system for the combined therapy due to its selectively retention in liver cancer cells, secondary to its morphological and physico-chemical properties of nanometric particle size, steady emulsion, proper organic and electronic surface.

Computational identification of a new SelD-like family that may participate in sulfur metabolism in hyperthermophilic sulfur-reducing archaea.

BACKGROUND: Selenium (Se) and sulfur (S) are closely related elements that exhibit similar chemical properties. Some genes related to S metabolism are also involved in Se utilization in many organisms. However, the evolutionary relationship between the two utilization traits is unclear. RESULTS: In this study, we conducted a comparative analysis of the selenophosphate synthetase (SelD) family, a key protein for all known Se utilization traits, in all sequenced archaea. Our search showed a very limited distribution of SelD and Se utilization in this kingdom. Interestingly, a SelD-like protein was detected in two orders of Crenarchaeota: Sulfolobales and Thermoproteales. Sequence and phylogenetic analyses revealed that SelD-like protein contains the same domain and conserved functional residues as those of SelD, and might be involved in S metabolism in these S-reducing organisms. Further genome-wide analysis of patterns of gene occurrence in different thermoproteales suggested that several genes, including SirA-like, Prx-like and adenylylsulfate reductase, were strongly related to SelD-like gene. Based on these findings, we proposed a simple model wherein SelD-like may play an important role in the biosynthesis of certain thiophosphate compound. CONCLUSIONS: Our data suggest novel genes involved in S metabolism in hyperthermophilic S-reducing archaea, and may provide a new window for understanding the complex relationship between Se and S metabolism in archaea.

Antitumoural hydroxyapatite nanoparticles-mediated hepatoma-targeted trans-arterial embolization gene therapy: in vitro and in vivo studies.

BACKGROUND/AIMS: Absence of curative treatment creates urgent need for new strategies for unresectable hepatoma. Based on former discoveries of good liver cell compatibility, safety and tumour-specific inhibition of hydroxyapatite nanoparticles (nHAP), this work tries to make nHAP serve as gene vector in the hepatoma-targeted trans-arterial embolization (TAE) gene therapy to elevate and synergize the therapeutic efficacy of TAE and target gene therapy. METHOD: Following dosage and ratio optimization, polypolex formed by surface modified nHAP and p53 expressing plasmid was applied in vitro for human hepatoma HePG2 cell, and then in vivo for rabbit hepatic VX2 tumour by injection of polypolex/lipodoil emulsion to the hepatic artery in a tumour-target manner. RESULTS: In vitro, the polypolex transfected only about 5% HepG2 cells, but can elevate the inhibition of its growth and apoptosis in a much more degree while keeping safe to the normal hepatocyte line, L02. In vivo, the emulsion, with better dispersion than the polypolex and more specific tumour-target than lipiodol, mediated specific 4% p53 expression and antitumoural nanoparticle retention in the target tumour site, also significantly reduced tumour growth and prolonged the animal survival times more than the lipiodol (P < 0.05). CONCLUSIONS: In all, this new treatment based on nHAP can enhance therapeutic effect of HCC safely both in vitro and in vivo.

Hepatic and biliary damage after transarterial chemoembolization for malignant hepatic tumors: incidence, diagnosis, treatment, outcome and mechanism.

OBJECTIVE: To provide an overview of recent studies on transarterial chemoembolization-related hepatic and biliary damage (TRHBD) in patients with malignant hepatic tumors (MHT) and to explore the reasons for TRHBD. METHODS: Literature on the treatments for MHT by TACE was sought in PubMed and the related information was summarized. RESULTS: TRHBD is found to occur in the hepatic parenchymal cells, biliary tree and blood-vascular system. The damage is mainly due to ischemia resulting from embolic materials such as gelatin sponge and lipiodol. In addition, clinicians' skill levels in non-superselective catheterization, the health condition of the patients, and the chemical agents used may also be related to the damage. Most of the deterioration can be reversed if the patients are diagnosed and treated properly and promptly. CONCLUSIONS: Understanding the mechanisms of TRHBD more comprehensively is helpful in developing effective methods for prevention and treatment.

[The effects of lipiodol-hydroxyapatite nanoparticle on apoptosis, proliferation, and angiogenesis in hepatic tumor: experiment with rabbits].

OBJECTIVE: To investigate the effects of lipiodol-hydroxyapatite nanoparticle (lipi-nHAP) on the growth, necrosis, apoptosis, proliferation, and angiogenesis of hepatic tumor. METHODS: Ultrasound-emulsification was used to make lipi-nHAP Eighty New Zealand white rabbits underwent implantation of carcinoma cells of the line VX2 into the left lobe of liver. Two weeks later the rabbits underwent catheterization into the gastroduodenal artery so that, and then the rabbits were randomly divided into four equal groups to receive infusion via the hepatic artery of different drugs: physiological saline (Group A), lipiodol (Group B), adriamycin + lipiodol (Group C), and lipi-nHAP (Group D). Seven and 14 days after the treatment the size of tumor was observed by spiral CT scan, and the volume and growth rate of tumor were calculated. Two weeks after the treatment 8 rabbits from each group were killed and their liver tumors were taken out and the survival rates of remaining rabbits were observed. The necrosis rate of the liver tumor was assessed by measuring the area of the tumor and the necrosis. The apoptotic rate was examined by TUNEL method. Mcrovessel density (MVD) was examined by immunohistochemistry anti-CD31 antibody. Anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody was used to detect the expression of PCNA so as to calculate the proliferation index of the cells. RESULTS: The tumor volume and growth rate of Group D 7 and 14 days after treatment were both significantly lower than those of other groups (all P < 0.05) and the necrosis rate and apoptotic index of Group D were both significantly higher than those of other groups (all P < 0.05). The values of MVD were higher in Groups C and D compared with those of Group A. Compared with those in other groups, the values of MVD and expression level of PCNA were significantly lower in group D (all P < 0.05). The survival time of Group D was longer than those of other groups (all P < 0.05). CONCLUSION: lipi-nHAP can suppress the growth of tumor, increase the tumor's necrosis rate and apoptotic index, inhibit the development of neovascularization, decrease the expression level of PCNA of residual tumor, and prolong the surviving time of the animals with hepatic tumor. It may become an effective embolization material to treat liver cancer.