Structural features of cholesteryl ester transfer protein: a molecular dynamics simulation study.

Cholesteryl ester transfer protein (CETP) mediates the net transfer of cholesteryl esters (CEs) from atheroprotective high-density lipoproteins (HDLs) to atherogenic low-density lipoproteins (LDLs) or very-low-density lipoproteins (VLDLs). Inhibition of CETP raises HDL cholesterol (good cholesterol) levels and reduces LDL cholesterol (bad cholesterol) levels, making it a promising drug target for the prevention and treatment of coronary heart disease. Although the crystal structure of CETP has been determined, the molecular mechanism mediating CEs transfer is still unknown, even the structural features of CETP in a physiological environment remain elusive. We performed molecular dynamics simulations to explore the structural features of CETP in an aqueous solution. Results show that the distal portion flexibility of N-terminal ß-barrel domain is considerably greater in solution than in crystal; conversely, the flexibility of helix X is slightly less. During the simulations the distal end of C-terminal ß-barrel domain expanded while the hydrophilic surface increasing more than the hydrophobic surface. In addition, a new surface pore was generated in this domain. This surface pore and all cavities in CETP are stable. These results suggest that the formation of a continuous tunnel within CETP by connecting cavities is permitted in solution.

Inhibition of osteosarcoma cell proliferation in vitro and tumor growth in vivo in mice model by alstonine through AMPK-activation and PGC-1α/TFAM up-regulation.

Osteosarcoma, a leading malignant tumor of bones is diagnosed mostly in adolescents and young adults worldwide. The present study investigated alstonine as anti-osteosarcoma agent in vitro as well as in vivo and evaluated the underlying mechanism. Treatment with alstonine led to a significant (P<0.05) reduction in MG63 and U-2OS cell viability. Alstonine treatment of MG63 and U-2OS cells caused a significant reduction in colony formation compared to the control cells. Viability of osteoblasts was not affected by alstonine treatment in 1.25 to 20 µM concentration range. In alstonine treated MG63 and U-2OS cells apoptotic cells increased significantly (P<0.05) compared to the control cells. Moreover, in MG63 and U-2OS cells treatment with alstonine caused a prominent increase in expression of cleaved caspase-9, caspase-3, and PARP. Treatment of MG63 and U-2OS cells with alstonine caused a prominent increase in AMPKα (Thr172) phosphorylation and elevated the count of mtDNA copies compared to the untreated cells. Alstonine treatment of the cells caused a remarkable increase in expression of PGC-1α and TFAM proteins. Treatment of the mice with alstonine at 5 and 10 mg/kg doses for 30 days caused a significant (P<0.05) reduction in xenograft growth. Expression of PGC-1α and TFAM proteins in tumor tissues of the mice treated with alstonine was significantly (P<0.05) raised compared to the control group. Thus, alstonine inhibits osteosarcoma cell growth and activates apoptosis through AMPK dependent pathway. Therefore, alstonine may be considered for treatment of osteosarcoma as it effectively arrests tumor growth in mice.

The electrochemical performance of fluorinated ketjenblack as a cathode for lithium/fluorinated carbon batteries.

The inferior rate capacity of lithium/fluorinated carbon (Li/CF x ) batteries limits their application in the field, requiring large discharge current and high power density. Herein, we report a novel type of fluorinated carbon with superior performance through gas-phase fluorination of ketjenblack. The investigation shows that the F/C ratio of the fluorinated ketjenblack (FKB) increases with the fluorination temperature, whereas the discharge voltage decreases due to the lowered content of semi-ionic C-F bonds. Accordingly, a suitable fluorination temperature of 520 °C was selected, under which the product exhibits the largest specific capacity of 924.6 mA h g-1 with discharge potential exceeding 3.1 V (vs. Li/Li+) and the highest energy density of 2544 W h kg-1 with power density of 27 493 W kg-1. This energy density is higher than the theoretical energy density of commercial fluorinated graphite (2180 W h kg-1). In addition, the sample delivers good rate capability demonstrated by a specific capacity retention ratio of 79.5% even at a current density of 20C. Therefore, the FKB material may have very promising practical applications in lithium primary batteries.

LncRNA FLVCR1-AS1 accelerates osteosarcoma cells to proliferate, migrate and invade via activating wnt/ß-catenin pathway.

PURPOSE: To clarify the biological function of long non-coding RNA (lncRNA) FLVCR1-AS1 in the progression of osteosarcoma. METHODS: The correlation between FLVCR1-AS1 level and pathological indexes of osteosarcoma patients was analyzed by chi-square test. Subsequently, the regulatory effects of FLVCR1-AS1 on the proliferative, migratory and invasive abilities of osteosarcoma cells were evaluated. Moreover, the relative levels of CTNNB1, SOX4, CCND1, CCND2 and MYC in osteosarcoma cells regulated by FLVCR1-AS1 were detected by qRT-PCR. Finally, rescue experiments were conducted to verify the role of wnt/ß-catenin in osteosarcoma progression. RESULTS: LncRNA FLVCR1-AS1 was upregulated in osteosarcoma, which was positively correlated to tumor size, WHO grade and distant metastasis, but negatively correlated to survival of osteosarcoma patients. Overexpression of FLVCR1-AS1 markedly suppressed osteosarcoma cells to proliferate, migrate and invade. Relative levels of CTNNB1, SOX4, CCND1, CCND2, MYC and nucleus ß-catenin were upregulated in U2OS and MG63 cells overexpressing FLVCR1-AS1. Finally, CTNNB1 knockdown was identified to reverse the influence of overexpressed FLVCR1-AS1 of osteosarcoma cells. CONCLUSIONS: FLVCR1-AS1 accelerates the progression of osteosarcoma via activating wnt/ß-catenin pathway.

Synthesis of silver @hydroxyapatite nanoparticles based biocomposite and their assessment for viability of Osseointegration for rabbit knee joint anterior cruciate ligament rehabilitation.

In this examination, chitosan-silk fibroin/polyethylene terephthalate (CTS-SF/PET), chitosan-silk fibroin/polyethylene terephthalate/hydroxyapatite (CTS-SF/PET/HAP) and chitosan-silk fibroin/polyethylene terephthalate/Silver @hydroxyapatite (CTS-SF/PET/Ag@HAP) scaffolds were prepared by utilizing the plasma splashing procedure. Field emission scanning electron microscopy (FESEM) results demonstrated that the outside of the PET covered with HAP nanoparticles. The cell viability results demonstrated that the number of Mesenchymal stem cells (MSCs) primarily spread out on CTS-SF/PET/Ag@HAP. RT-PCR results demonstrated that there was an upregulated mRNA articulation of osseous development-related properties in the CTS-SF/PET/Ag@HAP composite. The in vivo rabbit animal assessment scores of the CTS-SF/PET/Ag@HAP composite were significantly better than those of the CTS-SF/PET at 1 to 3 months. Both in-vivo and in-vitro results exhibited in this investigation recommend that the cytocompatibility and osseointegration of CTS-SF/PET/Ag@HAP tendon were fundamentally improved by expanding the multiplication of cells and up-regulating the outflow of tendon development-related properties. In conclusion, the CTS-SF/PET/Ag@HAP tendon is a promising candidate for Anterior Cruciate Ligament (ACL) replacement in the future.