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Latest Paper:
Pharmazie. 2012 Apr ;67 (4):299-303
22570935
Orthopedics Department, General Hospital of Chinese PLA, Beijing, China.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a critical regulator of osteogenic capacity that is commonly used in bone grafts. The effectiveness of rhBMP-2 may be reduced as it can become unstable and degraded after injection into the body. Microspheres are considered appropriate vehicles for the sustained release of proteins in vivo. In this study, rhBMP-2 microspheres were manufactured using the water-in-oil-in-water (W/O/W) double-emulsion solvent-extraction technique by encapsulation in poly(lactic-co-glycolic) acid (PLGA). The microspheres were then embedded in two hydrogels made of either poloxamer 407 hydrogel or chitosan thioglycolic acid (CS-TA). The encapsulation efficiency and in vitro release of rhBMP-2 were examined and compared with the control release system (rhBMP-2 microspheres alone). The rhBMP-2 microspheres in the CS-TA hydrogel showed the lowest burst release (about 40% in the first 8h) among the three groups. The mechanisms may be the high viscosity of CS-TA hydrogel and the sustained release characteristics of CS-TA itself. The CS-TA hydrogel combined with PLGA microspheres can efficiently encapsulate rhBMP-2, control the burst release at early time points, and provide sustained release in vitro. It may be an appropriate rhBMP-2 vehicle for bone regeneration.
S Chatrchyan,
V Khachatryan,
A M Sirunyan,
A Tumasyan,
W Adam,
T Bergauer,
M Dragicevic,
J Erö,
C Fabjan,
M Friedl,
R Frühwirth,
V M Ghete,
J Hammer,
M Hoch,
N Hörmann,
J Hrubec,
M Jeitler,
W Kiesenhofer,
M Krammer,
D Liko,
I Mikulec,
M Pernicka,
B Rahbaran,
C Rohringer,
H Rohringer,
R Schöfbeck,
J Strauss,
A Taurok,
F Teischinger,
P Wagner,
W Waltenberger,
G Walzel,
E Widl,
C-E Wulz,
V Mossolov,
N Shumeiko,
J Suarez Gonzalez,
S Bansal,
L Benucci,
T Cornelis,
E A De Wolf,
X Janssen,
S Luyckx,
T Maes,
L Mucibello,
S Ochesanu,
B Roland,
R Rougny,
M Selvaggi,
H Van Haevermaet,
P Van Mechelen,
N Van Remortel,
A Van Spilbeeck,
F Blekman,
S Blyweert,
J D'Hondt,
R Gonzalez Suarez,
A Kalogeropoulos,
M Maes,
A Olbrechts,
W Van Doninck,
P Van Mulders,
G P Van Onsem,
I Villella,
O Charaf,
B Clerbaux,
G De Lentdecker,
V Dero,
A P R Gay,
G H Hammad,
T Hreus,
A Léonard,
P E Marage,
L Thomas,
C Vander Velde,
P Vanlaer,
J Wickens,
V Adler,
K Beernaert,
A Cimmino,
S Costantini,
G Garcia,
M Grunewald,
B Klein,
J Lellouch,
A Marinov,
J McCartin,
A A Ocampo Rios,
D Ryckbosch,
N Strobbe,
F Thyssen,
M Tytgat,
L Vanelderen,
P Verwilligen,
S Walsh,
E Yazgan,
N Zaganidis,
S Basegmez,
G Bruno,
L Ceard,
J De Favereau De Jeneret,
C Delaere,
T du Pree,
D Favart,
L Forthomme,
A Giammanco,
G Grégoire,
J Hollar,
V Lemaitre,
J Liao,
O Militaru,
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C Lazaridis,
J Leonard,
R Loveless,
A Mohapatra,
I Ojalvo,
G A Pierro,
I Ross,
A Savin,
W H Smith,
J Swanson
Yerevan Physics Institute, Yerevan, Armenia.
A search for a Higgs boson in the four-lepton decay channel H→ZZ, with each Z boson decaying to an electron or muon pair, is reported. The search covers Higgs boson mass hypotheses in the range of 110<m_{H}<600 GeV. The analysis uses data corresponding to an integrated luminosity of 4.7 fb^{-1} recorded by the CMS detector in pp collisions at sqrt[s]=7 TeV from the LHC. Seventy-two events are observed with four-lepton invariant mass m_{4ℓ}>100 GeV (with 13 below 160 GeV), while 67.1±6.0 (9.5±1.3) events are expected from background. The four-lepton mass distribution is consistent with the expectation of standard model background production of ZZ pairs. Upper limits at 95% confidence level exclude the standard model Higgs boson in the ranges of 134-158 GeV, 180-305 GeV, and 340-465 GeV. Small excesses of events are observed around masses of 119, 126, and 320 GeV, making the observed limits weaker than expected in the absence of a signal.
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M Weinberg
Yerevan Physics Institute, Yerevan, Armenia.
A search for signatures of extra spatial dimensions in the diphoton invariant-mass spectrum has been performed with the CMS detector at the LHC. No excess of events above the standard model expectation is observed using a data sample collected in proton-proton collisions at sqrt[s]=7 TeV corresponding to an integrated luminosity of 2.2 fb^{-1}. In the context of the large-extra-dimensions model, lower limits are set on the effective Planck scale in the range of 2.3-3.8 TeV at the 95% confidence level. These limits are the most restrictive bounds on virtual-graviton exchange to date. The most restrictive lower limits to date are also set on the mass of the first graviton excitation in the Randall-Sundrum model in the range of 0.86-1.84 TeV, for values of the associated coupling parameter between 0.01 and 0.10.
PLoS One. 2012 ;7 (4):e34633
22514649
Laboratory of Innate Immunity and Inflammation, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.
The neutrophil gelatinase-associated lipocalin 2 (LCN2) is a critical inflammatory mediator persistently induced during endotoxemia, contributing to tubular damage and kidney failure. The intracellular process responsible for persistent induction of LCN2 by bacterial endotoxin Lipopolysaccharide (LPS) is not well understood. Using primary kidney fibroblasts, we observed that LPS-induced LCN2 expression requires a coupled circuit involving an early transient phase of AP-1 path and a late persistent phase of C/EBPδ path, both of which are dependent upon the interleukin 1 receptor associated kinase 1 (IRAK-1). Using immunoprecipitation analysis we observed transient binding of AP-1 to the promoters of both TNFα and C/ebpδ. On the other hand, we only observed persistent binding of C/EBPδ to its own promoter but not on TNFα. Blockage of new protein synthesis using cyclohexamide significantly reduced the expression of C/EBPδ as well as LCN2. By chromatin immunoprecipitation analyses, we demonstrated that LPS recruited C/EBPδ to the Lcn2 promoter in WT, but not IRAK-1 deficient fibroblasts. A differential equation-based computational model captured the dynamic circuit leading to the persistent induction of LCN2. In vivo, we observed elevated levels of LCN2 in kidneys harvested from LPS-injected WT mice as compared to IRAK-1 deficient mice. Taken together, this study has identified an integrated intracellular network involved in the persistent induction of LCN2 by LPS.
PLoS One. 2012 ;7 (4):e32283
22514598
Deying Yang,
Yan Fu,
Xuhang Wu,
Yue Xie,
Huaming Nie,
Lin Chen,
Xiang Nong,
Xiaobin Gu,
Shuxian Wang,
Xuerong Peng,
Ning Yan,
Runhui Zhang,
Wanpeng Zheng,
Guangyou Yang
Department of Parasitology, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an, China.
BACKGROUND Taenia pisiformis is one of the most common intestinal tapeworms and can cause infections in canines. Adult T. pisiformis (canines as definitive hosts) and Cysticercus pisiformis (rabbits as intermediate hosts) cause significant health problems to the host and considerable socio-economic losses as a consequence. No complete genomic data regarding T. pisiformis are currently available in public databases. RNA-seq provides an effective approach to analyze the eukaryotic transcriptome to generate large functional gene datasets that can be used for further studies. METHODOLOGY/PRINCIPAL FINDINGS In this study, 2.67 million sequencing clean reads and 72,957 unigenes were generated using the RNA-seq technique. Based on a sequence similarity search with known proteins, a total of 26,012 unigenes (no redundancy) were identified after quality control procedures via the alignment of four databases. Overall, 15,920 unigenes were mapped to 203 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Through analyzing the glycolysis/gluconeogenesis and axonal guidance pathways, we achieved an in-depth understanding of the biochemistry of T. pisiformis. Here, we selected four unigenes at random and obtained their full-length cDNA clones using RACE PCR. Functional distribution characteristics were gained through comparing four cestode species (72,957 unigenes of T. pisiformis, 30,700 ESTs of T. solium, 1,058 ESTs of Eg+Em [conserved ESTs between Echinococcus granulosus and Echinococcus multilocularis]), with the cluster of orthologous groups (COG) and gene ontology (GO) functional classification systems. Furthermore, the conserved common genes in these four cestode species were obtained and aligned by the KEGG database. CONCLUSION This study provides an extensive transcriptome dataset obtained from the deep sequencing of T. pisiformis in a non-model whole genome. The identification of conserved genes may provide novel approaches for potential drug targets and vaccinations against cestode infections. Research can now accelerate into the functional genomics, immunity and gene expression profiles of cestode species.
Int J Mol Med. 2012 Mar 13;:
22426464
Sang-Seok Oh,
Chaerin Moon,
Dong-Hyeok Kim,
Hyunkeun Song,
Saegwang Park,
Yangxin Fu,
Kwang Dong Kim
Division of Applied Life Science (BK21), PMBBRC, Gyeongsang National University, Jinju, Republic of Korea.
Type I interferons (IFNs), including IFN-β, are known to enhance antigen (Ag) presentation and to promote the expansion, survival and effector function of CD8+ cytotoxic lymphocytes (CTL) during viral infections. Furthermore, IFN-β is a potent candidate for antitumor drugs; however, recombinant IFN-β is too unstable for use in tumor therapy in vivo. In this study, we therefore examined the efficacy and mechanism of exogenous IFN-β as a biomolecule for tumor therapy, using adenovirus encoding IFN-β (Ad-IFNβ) as a therapeutic agent in a mouse model. Ag104Ld and 4T1 tumor cells exposed to Ad-IFNβ showed growth retardation and cell death in vitro, and tumor growth as well as tumor metastasis was inhibited in vivo. The Ad-IFNβ-mediated antitumor effect was dependent on CD8+ T cells in vivo, rather than on a direct cytotoxic effect of Ad-IFNβ. Transient T lymphocyte depletion was observed in tumor tissue after intratumoral injection with Ad-IFNβ. Despite the T lymphocyte depletion, the proliferation of Ag-specific CD8+ T cells was increased in Ad-IFNβ-treated mice compared to control virus-treated mice. These results suggest that IFN-β might contribute to the inhibition of tumor growth by depleting Ag-nonspecific T lymphocytes and enhancing proliferation of Ag-specific CD8+ T cells.
Eur J Surg Oncol. 2012 Mar 12;:
22417704
The Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225 Changhai Road, Shanghai 200438, PR China.
BACKGROUND: The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is currently unsatisfactory. The aims of this study were to identify prognostic factors after curative ICC resection, and to evaluate the effects of postoperative transcatheter arterial chemoembolisation (TACE). METHODS: A retrospective analysis was conducted of 114 ICC patients who underwent curative resection from January 2005 to December 2006. Relationships between survival and clinicopathological factors were evaluated using univariate and multivariate analyses. The benefits of adjuvant TACE were investigated separately. RESULTS: The cumulative 1-, 3-, and 5-year survival rates were 63%, 26%, and 15%, respectively. Multivariate analysis revealed that tumour size ≥5cm (hazard ratio [HR] 1.875, 95% CI 1.139-3.088, P=0.013) and advanced TNM stage (stage III or IV)(HR 1.681, 95% CI 1.035-2.732, P=0.036) were independently associated with poor prognosis. Fifty-seven patients underwent adjuvant TACE. In patients with poor prognostic factors, TACE improved the survival rate (P<0.001). However, in patients without poor prognostic factors, TACE did not significantly change the survival rate (P=0.724). CONCLUSIONS: Postoperative adjuvant TACE can prolong survival in ICC patients with tumour size ≥5cm or advanced TNM stage.
Fitoterapia. 2012 Mar 4;:
22414318
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China.
It is difficult to develop injectable sustained delivery systems for herbal medicines because of their composition complexity. Encapsulating various compounds with different physiochemical properties and achieving their synchronized and sustained release seem too hard to realize. In this paper, an injectable nanoparticulate system based on an mPEG-PLGA-mPEG (PELGE) platform was prepared for co-encapsulation and sustained release of four active components (ginkgolides A, B, C and bilobalide) in Ginkgo biloba extract. Different carriers were screened by macrophage uptake experiment for their ability to be long-circulation. Drug loaded nanoparticles were prepared with 10% PEG(2000) modified PLGA by a co-precipitation method. The encapsulation efficiency of the total ginkgo terpenes (GT) in the optimal formulation was 78.84±2.06% with a loading dose of 11.90±0.31mg/150mg PELGE. The particles exhibited a spherical shape with a mean diameter of 123.3±44.0nm and zeta potential of -30.86±2.49mV. Sustained and synchronized release of the four components from PELGE nanoparticles was observed both in vitro and in vivo, which was mainly contributed to the long circulation of PEGylated nanoparticles and the slow degradation of PLGA. The half-life time of the four terpenoid compounds were also significantly improved by incorporation into PELGE nanoparticles. The results indicate that a PELGE nanoparticle is a promising carrier system for sustained and synchronized release of herbal medicines containing multiple components.
FEMS Microbiol Lett. 2012 Mar 9;:
22404599
Center of Biomedical and Health, Hangzhou Normal University, Hangzhou, China; Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences.
Presequences play an important role in protein import into mitochondria-like organelles. Acquisition pathways have been revealed for some mitochondrial presequences. However, little has been known about hydrogenosomal presequences. In this article, we investigated the hydrogenosomal proteins of Trichomonas vaginalis and suggest that several hydrogenosomal presequences probably evolved from pre-existing sequences that were thereafter modified. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Research Institute of Photocatalysis, Fujian Provincial Key Laboratory of Photocatalysis, State Key Laboratory Breeding Base, Fuzhou University, Fuzhou 350002 (People's Republic of China).
Let your light shine: The photocatalytic reduction of carbon dioxide to the formate anion under visible light irradiation is for the first time realized over a photoactive Ti-containing metal-organic framework, NH(2)-MIL-125(Ti), which is fabricated by a facile substitution of ligands in the UV-responsive MIL-125(Ti) material (see scheme; TEOA=triethanolamine).
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