EPS can decrease the risk of screw loosening and achieve better fixation strength and clinical results in osteoporotic lumbar spine fusion.

Like bone marrow stromal cells, adipose tissue-derived stem cells (ADSCs) possess multilineage potential, a capacity for self-renewal and long-term viability. To confirm whether ADSCs represent a promising source of cells for gene-enhanced bone tissue-engineering, the osteogenic potential of ADSCs under the control of certain osteoinductive genes has been evaluated. Runx2, a transcription factor at the downstream end of bone morphogenetic protein (BMP) signaling pathways, is essential for osteoblast differentiation and bone formation. In this study we used adenovirus vector to deliver Runx2 to ADSCs and then examined the enhancement of osteogenic activity. Overexpression of Runx2 inhibited adipogenesis, as demonstrated by suppression of LPL and PPARgamma expression at the mRNA level and reduced lipid droplet formation. Moreover, ADSCs transduced with Ad-Runx2 underwent rapid and marked osteoblast differentiation as determined by osteoblastic gene expression, alkaline phosphatase activity and mineral deposition. Additionally, histological examination revealed that implantation of Runx2 modified ADSCs could induce mineral deposition and bone-like tissue formation in vivo. These results confirmed, firstly, the ability of Runx2 to promote osteogenesis and cell differentiation and, secondly, the competence of ADSCs as target cells for bone tissue engineering. Our work demonstrates a potential new approach for bone repair using Runx2-modified ADSCs for bone tissue engineering.

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Icariin, the main active compound of the traditional Chinese medicine, Epimedium, is commonly used for the clinical treatment of osteoporosis. However, the precise molecular mechanism of the therapeutic effect of icariin has not been elucidated. The aim of this study was to examine the effect of icariin on cell viability, alkaline phosphatase (ALP) activity, the amount of calcified nodules, and to delineate the molecular mechanism of icariin-enhanced bone formation by investigating the expression of bone morphogenic protein-2 (BMP-2), Smad4, Cbfa1/Runx2, osteoprotegerin (OPG), receptor activator of nuclear factor κ-B ligand (RANKL) and the OPG/RANKL ratio in the hFOB 1.19 human osteoblastic cell line. We found that icariin significantly increased the cell viability, the activity of ALP and the amount of calcified nodules in the hFOB 1.19 cells. Furthermore, we observed that icariin upregulated the expression of BMP-2, Smad4, Cbfa1/Runx2, OPG, RANKL and the OPG/RANKL ratio. Our results indicate that icariin can modulate the process of bone formation via the BMP-2/Smad4 signal transduction pathway in hFOB 1.19 cells.

A gene cluster responsible for the biosynthesis of anticancer agent FK228 has been identified, cloned, and partially characterized in Chromobacterium violaceum no. 968. First, a genome-scanning approach was applied to identify three distinctive C. violaceum no. 968 genomic DNA clones that code for portions of nonribosomal peptide synthetase and polyketide synthase. Next, a gene replacement system developed originally for Pseudomonas aeruginosa was adapted to inactivate the genomic DNA-associated candidate natural product biosynthetic genes in vivo with high efficiency. Inactivation of a nonribosomal peptide synthetase-encoding gene completely abolished FK228 production in mutant strains. Subsequently, the entire FK228 biosynthetic gene cluster was cloned and sequenced. This gene cluster is predicted to encompass a 36.4-kb DNA region that includes 14 genes. The products of nine biosynthetic genes are proposed to constitute an unusual hybrid nonribosomal peptide synthetase-polyketide synthase-nonribosomal peptide synthetase assembly line including accessory activities for the biosynthesis of FK228. In particular, a putative flavin adenine dinucleotidedependent pyridine nucleotide-disulfide oxidoreductase is proposed to catalyze disulfide bond formation between two sulfhydryl groups of cysteine residues as the final step in FK228 biosynthesis. Acquisition of the FK228 biosynthetic gene cluster and acclimation of an efficient genetic system should enable genetic engineering of the FK228 biosynthetic pathway in C. violaceum no. 968 for the generation of structural analogs as anticancer drug candidates. FK228 (C 24 H 36 N 4 O 6 S 2 ; molecular weight, 540.2) ( Fig. 1), also known as FR901228 or depsipeptide and registered as NSC 630176 or romidepsin, is a natural product discovered in the fermentation broth of Chromobacterium violaceum no. 968 in a screening program for agents that reverse the malignant phenotype of a Ha-ras oncogene-transformed NIH 3T3 cell line (51, 52). It exhibited outstanding anticancer activities against an array of tumor cell lines, including many members of a standard panel of 60 cell lines from the U.S. National Cancer Institute (18, 53). FK228 has entered extensive clinical trials and has shown promising properties as a new type of anticancer drug (5,30,35,36,41). A multinational pivotal trial of FK228 for the treatment of cutaneous T-cell lymphoma has been launched by Gloucester Pharmaceuticals, Inc., and the company plans to file for U.S. Food and Drug Administration approval in late 2007.Structurally, FK228 is a bicyclic depsipeptide that features a 16-membered macrolactone ring containing an ester linkage and a 17-membered ring containing the same ester linkage and a disulfide bond, the latter of which endows FK228 with an unprecedented molecular scaffold (Fig. 1). Its structure was determined by spectroscopic and X-ray crystallographic analyses (45) and was confirmed by total synthesis (27). A close examination of the FK228 structure identified building blocks of three amino acids (D-cy...

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An 8‐week feeding trial was conducted to assess dietary protein and lipid levels on growth performance, feed utilization and body composition of juvenile red‐spotted grouper (7.85 ± 0.03 g fish−1). Nine semi‐purified diets were formulated containing varying protein levels (440–520 g kg−1, dry matter) and lipid levels (60–120 g kg−1, dry matter). The weight gain of juvenile Epinephelus akaara was affected by dietary protein (p = .005) and its interaction with dietary lipid (p = .020). Viscerosomatic index, intraperitoneal fat ratio and whole‐body lipid level increased with increasing dietary lipid level (p < .001). Nitrogen retention was not affected by dietary protein and lipid, while lipid retention decreased with increasing dietary lipid level (p < .001). The plasma blood urea nitrogen increased with increasing dietary protein level (p = .003). This study showed that diet with 520 g kg−1 protein and 60 g kg−1 lipid with 30.58 mg kJ−1 P:E provided a maximal growth for this species. Moreover, an increase in dietary lipid levels (from 60 to 90 g kg−1) could reduce the protein requirement (from 520 to 480 g kg−1) without affecting the growth performance, while higher fat deposition was observed in fish fed high‐lipid diets.

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