A bone scaffold material (nano-HA/ collagen/PLA composite) was developed by biomimetic synthesis. It shows some features of natural bone both in main composition and hierarchical microstructure. Nano-hydroxyapatite and collagen assembled into mineralized fibril. The three-dimensional porous scaffold materials mimic the microstructure of cancellous bone. Cell culture and animal model tests showed that the composite material is bioactive. The osteoblasts were separated from the neonatal rat calvaria. Osteoblasts adhered, spread, and proliferated throughout the pores of the scaffold material within a week. A 15-mm segmental defect model in the radius of the rabbit was used to evaluate the bone-remodeling ability of the composite. Combined with 0.5 mg rhBMP-2, the material block was implanted into the defect. The segmental defect was integrated 12 weeks after surgery, and the implanted composite was partially substituted by new bone tissue. This scaffold composite has promise for the clinical repair of large bony defects according to the principles of bone tissue engineering.

A designed hierarchical structure was made by self-assembly of nano-fibrils of mineralized collagen resembling extracellular matrix. The collagen fibrils were formed by self-assembly of collagen triple helices. Hydroxyapatite (HA) crystals grew on the surface of these fibrils in such a way that their c-axes were oriented along the longitudinal axes of the fibrils. The mineralized collagen fibrils aligned parallel to each other to form mineralized collagen fibers. For the first time, the new hierarchical self-assembly structure of collagen−hydroxyapatite composite was verified by conventional and high-resolution transmission electron microscopy.

APOBEC3G (also known as CEM15) is an innate intracellular antiretroviral factor that is counteracted by the Vif protein of lentiviruses. While APOBEC3G orthologues from several species are active against a broad range of retroviruses, given Vif proteins have a narrow spectrum of activity. For instance, HIV-1 Vif efficiently blocks APOBEC3G from human but not African green monkey (AGM), whereas the reverse is observed with SIV AGM Vif. Here, we demonstrate that a single amino acid at position 128 of human and AGM APOBEC3G governs the virus-specific sensitivity of these proteins to Vif-mediated inhibition. Furthermore, we show that this phenotype correlates with the ability of Vif to bind APOBEC3G and interfere with its incorporation into virions. These results shed light on an important determinant of the tropism of primate lentiviruses.The replication of a virus within its host and its spread to a new species require that innate lines of defense be overcome. APOBEC3G 1 is a cytidine deaminase that confers broad protection against retroviruses and limits the cross-species transmission of these pathogens (1-5). Packaged during viral assembly, APOBEC3G associates with the retroviral reverse transcription complex, where it deaminates cytosine residues to uracil in the growing minus-strand viral DNA (4 -7). These U-rich transcripts are either degraded or yield proviruses that are largely non-functional due to G-to-A hypermutation. APOBEC3G is counteracted by the Vif (virion infectivity factor) protein of lentiviruses, which associates with the enzyme to prevent its virion incorporation and trigger its proteasomal degradation (5, 8 -12). In the absence of Vif, human APOBEC3G is active against a broad spectrum of retroelements, as it can inhibit the replication of lentiviruses such as human and simian immunodeficiency virus (HIV and SIV, respectively) and equine infectious anemia virus (EIAV), of the gammaretrovirus murine leukemia virus (MLV) (4, 7), and of the hepadnavirus hepatitis B virus (13). APOBEC3G orthologues are also effective against several of these viruses. Vifdefective HIV-1, for instance, is blocked by APOBEC3G from human, rhesus macaque, African green monkey, and mouse (5). In contrast, a far greater degree of specificity is noted in the Vif sensitivity of these antiviral factors. As an example, the Vif protein of HIV-1 can only counter human and chimpanzee APOBEC3G, but is ineffective against the rhesus macaque, AGM, and mouse orthologues of the enzyme. Conversely, Vif from SIV AGM is active against AGM but not human APOBEC3G (5). Here, we took advantage of these speciesspecific differences to explore further the mechanism of Vif action. EXPERIMENTAL PROCEDURESExpression Vectors-Wild type and vif-defective HIV-1 proviral clones were described previously (14). To permit its trans-expression, a His-tagged form of HIV-1 Vif was inserted into the pEF1/Myc-His plasmid (Invitrogen), yielding the pEF1-VifHis plasmid. The plasmids expressing the HA-tagged form of huAPOBEC3G (3) and the SIV AGM.TAN Vif (pgVif/...

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Nanofibers exist widely in human tissue with different patterns. Electrospinning nanotechnology has recently gained a new impetus due to the introduction of the concept of biomimetic nanofibers for tissue regeneration. The advanced electrospinning technique is a promising method to fabricate a controllable continuous nanofiber scaffold similar to the natural extracellular matrix. Thus, the biomedical field has become a significant possible application field of electrospun fibers. Although electrospinning has developed rapidly over the past few years, electrospun nanofibers are still at a premature research stage. Further comprehensive and deep studies on electrospun nanofibers are essential for promoting their biomedical applications. Current electrospun fiber materials include natural polymers, synthetic polymers and inorganic substances. This review briefly describes several typically electrospun nanofiber materials or composites that have great potential for tissue regeneration, and describes their fabrication, advantages, drawbacks and future prospects.

Proteasomes are attractive emerging targets for anti-cancer therapies. Auranofin (Aur), a gold-containing compound clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer but its anti-cancer mechanism is poorly understood. Here we report that (i) Aur shows proteasome-inhibitory effect that is comparable to that of bortezomib/Velcade (Vel); (ii) different from bortezomib, Aur inhibits proteasome-associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; (iii) inhibition of the proteasome-associated DUBs is required for Aur-induced cytotoxicity; and (iv) Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from acute myeloid leukemia patients. This study provides important novel insight into understanding the proteasome-inhibiting property of metal-containing compounds. Although several DUB inhibitors were reported, this study uncovers the first drug already used in clinic that can inhibit proteasome-associated DUBs with promising anti-tumor effects.

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Purpose Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML. Gambogic acid, a small molecule derived from Chinese herb gamboges, has been approved for phase II clinical trial for cancer therapy by the Chinese Food and Drug Administration (FDA). In this study, we investigated the effect of gambogic acid on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Experimental Design CML cell lines (KBM5, KBM5-T315I, and K562), primary cells from patients with CML with clinical resistance to imatinib, and normal monocytes from healthy volunteers were treated with gambogic acid, imatinib, or their combination, followed by measuring the effects on cell growth, apoptosis, and signal pathways. The in vivo antitumor activity of gambogic acid and its combination with imatinib was also assessed with nude xenografts. Results Gambogic acid induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Our data suggest that GA-induced proteasome inhibition is required for caspase activation in both imatinib-resistant and -sensitive CML cells, and caspase activation is required for gambogic acid–induced Bcr-Abl downregulation and apoptotic cell death. Conclusions These findings suggest an alternative strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with the medicinal compound gambogic acid, which may have great clinical significance in imatinib-resistant cancer therapy.