Gene/Protein Disease Symptom Drug Enzyme Compound
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 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The employment of composite scaffolds with a well-organized architecture and multi-scale porosity certainly represents a valuable approach for achieving a tissue engineered construct to reproduce the middle and long-term behaviour of hierarchically complex tissues such as spongy bone. In this paper, fibre-reinforced composites scaffold for bone tissue engineering applications is described. These are composed of poly-L-lactide acid (PLLA) fibres embedded in a porous poly(epsilon-caprolactone) matrix, and were obtained by synergistic use of phase inversion/particulate leaching technique and filament winding technology. Porosity degree as high as 79.7% was achieved, the bimodal pore size distribution showing peaks at ca 10 and 200 microm diameter, respectively, accounting for 53.7% and 46.3% of the total porosity. In vitro degradation was carried out in PBS and SBF without significant degradation of the scaffold after 35 days, while in NaOH solution, a linear increase of weight lost was observed with preferential degradation of PLLA component. Subsequently, marrow stromal cells (MSC) and human osteoblasts (HOB) reached a plateau at 3 weeks, while at 5 weeks the number of cells was almost the same. Human marrow stromal cell and trabecular osteoblasts rapidly proliferate on the scaffold up to 3 weeks, promoting an oriented migration of bone cells along the fibre arrangement. Moreover, the role of seeded HOB and MSC on composite degradation mechanism was assessed by demonstrating a more relevant contribution to PLLA degradation of MSC when compared to HOB. The novel PCL/PLLA composite scaffolds thus showed promise whenever tuneable porosity, controlled degradability and guided cell-material interaction are simultaneously requested.
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PMID:Polylactic acid fibre-reinforced polycaprolactone scaffolds for bone tissue engineering. 1854 38

In an effort to achieve suitable biomaterials for peripheral nerve regeneration, we present a material design strategy of combining a crystallite-based physical network and a crosslink-based chemical network. Biodegradable polymer disks and conduits have been fabricated by photo-crosslinking three poly(epsilon-caprolactone fumarate)s (PCLF530, PCLF1250, and PCLF2000), which were synthesized from the precursor poly(epsilon-caprolactone) (PCL) diols with nominal molecular weights of 530, 1250, and 2000 g mol(-1), respectively. Thermal properties such as glass transition temperature (T(g)), melting temperature (T(m)), and crystallinity of photo-crosslinked PCLFs were examined and correlated with their rheological and mechanical properties. Furthermore, in vitro degradation of uncrosslinked and crosslinked PCLFs in PBS crosslinked PCLFs in 1 N NaOH aqueous solution at 37 degrees C was studied. In vitro cytocompatibility, attachment, and proliferation of Schwann cell precursor line SPL201 cells on three PCLF networks were investigated. Crosslinked PCLF2000 with the highest crystallinity and mechanical properties was found to best support cell attachment and proliferation. Using a new photo-crosslinking method, single-lumen crosslinked PCLF nerve conduits without defects were fabricated in a glass mold. Crosslinked PCLF2000 nerve conduits were selected for evaluation in a 1cm gap rat sciatic nerve model. Histological evaluation demonstrated that the material was biocompatible with sufficient strength to hold sutures in place after 6 and 17 weeks of implantation. Nerve cable with myelinated axons was found in the crosslinked PCLF2000 nerve conduit.
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PMID:Photo-crosslinked poly(epsilon-caprolactone fumarate) networks for guided peripheral nerve regeneration: material properties and preliminary biological evaluations. 1917 6

Near-infrared (NIR) fluorophores have several advantages over visible fluorophores, including improved tissue penetration and lower autofluorescence; however, only indocyanine green (ICG) is clinically approved. Its use in molecular imaging probes is limited because it loses its fluorescence after protein binding. This property can be harnessed to create an activatable NIR probe. After cell binding and internalization, ICG dissociates from the targeting antibody, thus activating fluorescence. ICG was conjugated to the antibodies daclizumab (Dac), trastuzumab (Tra), or panitumumab (Pan). The conjugates had almost no fluorescence in PBS but became fluorescent after SDS and 2-mercaptoethanol, with a quenching capacity of 10-fold for 1:1 conjugates and 40- to 50-fold for 1:5 conjugates. In vitro microscopy showed activation within the endolysosomes in target cells. In vivo imaging in mice showed that CD25-expressing tumors were specifically visualized with Dac-ICG. Furthermore, tumors overexpressing HER1 and HER2 were successfully characterized in vivo by using Pan-ICG(1:5) and Tra-ICG(1:5), respectively. Thus, we have developed an activatable NIR optical probe that "switches on" only in target cells. Because both the antibody and the fluorophore are Food and Drug Administration approved, the likelihood of clinical translation is improved.
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PMID:In vivo molecular imaging of cancer with a quenching near-infrared fluorescent probe using conjugates of monoclonal antibodies and indocyanine green. 1917 73

The purpose of this study was to develop a novel polymer cuff for the local delivery of alpha-lipoic acid (ALA) to inhibit neointimal formation in vivo. The polymer cuff was fabricated by incorporating the ALA into poly- (D,L-lactide-co-caprolactone) 40:60 (PLC), with or without methoxy polyethylene glycol (MethoxyPEG). The release kinetics of ALA and in vitro degradation by hydrolysis were analyzed by HPLC and field emission scanning electron microscopy (FE-SEM), respectively. In vivo evaluation of the effect of the ALA-containing polymer cuff was carried out using a rat femoral artery cuff injury model. At 24 h, 48% or 87% of the ALA was released from PCL cuffs with or without MethoxyPEG. FE-SEM results indicated that ALA was blended homogenously in the PLC with MethoxyPEG, whereas ALA was distributed on the surface of the PLC cuff without MethoxyPEG. The PLC cuff with MethoxyPEG showed prolonged and controlled release of ALA in PBS, in contrast to the PLC cuff without MethoxyPEG. Both ALA-containing polymer cuffs had a significant effect on the inhibition of neointimal formation in rat femoral artery. Novel ALA-containing polymer cuffs made of PLC were found to be biocompatible and effective in inhibiting neointimal formation in vivo. Polymer cuffs containing MethoxyPEG allowed the release of ALA for one additional week, and the rate of drug release from the PLC could be controlled by changing the composition of the polymer. These findings demonstrate that polymer cuffs may be an easy tool for the evaluation of anti-restenotic agents in animal models.
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PMID:Fabrication of an alpha-lipoic acid-eluting poly-(D,L-lactide-co-caprolactone) cuff for the inhibition of neointimal formation. 1928 97

Duchenne-Meryon muscular dystrophy (DMD) is the most common and lethal genetic muscle disease. Ameliorating muscle necrosis, inflammation, and fibrosis represents an important therapeutic approach for DMD. Imatinib, an antineoplastic agent, demonstrated antiinflammatory and antifibrotic effects in liver, kidney, lung, and skin of various animal models. This study tested antiinflammatory and antifibrotic effects of imatinib in mdx mice, a DMD mouse model. We treated mdx mice with intraperitoneal injections of imatinib at the peak of limb muscle inflammation and the onset of diaphragm fibrosis. Controls received PBS vehicle or were left untreated. Muscle necrosis, inflammation, fibrosis, and function were evaluated by measuring serum CK activity, endomysial CD45 immunoreactive inflammation area, endomysial collagen III deposition, and hind limb grip strength. Phosphorylation of the tyrosine kinase targets of imatinib was assessed by Western blot in diaphragm tissue and in primary cultures of peritoneal macrophages and skeletal muscle fibroblasts. Imatinib markedly reduced muscle necrosis, inflammation, and fibrosis, and significantly improved hind limb grip strength in mdx mice. Reduced clinical disease was accompanied by inhibition of c-abl and PDGFR phosphorylation and suppression of TNF-alpha and IL-1beta expression. Imatinib therapy for DMD may hold promise for ameliorating muscle necrosis, inflammation, and fibrosis by inhibiting c-abl and PDGFR signaling pathways and downstream inflammatory cytokine and fibrotic gene expression.
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PMID:Imatinib attenuates skeletal muscle dystrophy in mdx mice. 1928 3

A rapid and sensitive detection of staphylococcal enterotoxin B (SEB) was developed using a novel acoustic sensing technique: Resonant Acoustic Profiling (RAP), which utilizes high-frequency piezoelectric quartz resonators for monitoring biomolecular interactions. An automated four-channel instrument consisting of acoustic sensors covalently conjugated with anti-SEB antibodies was used. As the samples flowed across control and active sensors simultaneously, binding was measured as a change in the resonant frequency. The lower limit of detection (LLOD) for the label free direct format was 25 ng/mL. Detection sensitivity was increased by adding mass sequentially to the captured SEB on the sensor in the form of sandwich antibodies and biotin-avidin-based gold nanoparticles. The LLOD for the mass enhanced formats were 5 and 0.5 ng/mL of SEB, respectively. The lowest sensitivity corresponds to 1.3 fM in a 75 microL sample. The total assay time including the enhancement steps was less than 10 min. SEB was detected in both neat urine and PBS buffer-spiked samples, with linear correlations between resonant frequency signals and SEB concentrations (R(2) of 0.999 and 0.998, respectively). No significant cross-reactivity was observed with homologue toxins SEA, SED, and TSST, but some cross-reactivity was observed with the closely related toxin SEC(1) when we used a polyclonal antibody in the assay. SEC(1) cross-reactivity was not observed when a SEB-specific monoclonal antibody was employed in the assay. Thus the specificity of the assay presented here was dependent on the quality of the antibodies used. In addition to detection, we evaluated RAP's ability to measure the toxin in unknown samples rapidly by measuring the initial binding rate of the interaction, thereby further shortening the assay time to 6 min.
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PMID:Quantitative detection of staphylococcal enterotoxin B by resonant acoustic profiling. 1937 26

Our previous study showed that nanoemulsion-encapsulated MAGE1-HSP70/SEA (MHS) complex protein vaccine elicited MAGE-1 specific immune response and antitumor effects against MAGE-1-expressing tumor and nanoemulsion is a useful vehicle with possible important implications for cancer biotherapy. The purpose of this study was to compare the immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70 and SEA as NE(MHS) vaccine following different administration routes and to find out the new and effective immune routes. Nanoemulsion vaccine was prepared using magnetic ultrasound methods. C57BL/6 mice were immunized with NE(MHS) via po., i.v., s.c. or i.p., besides mice s.c. injected with PBS or NE(-) as control. The cellular immunocompetence was detected by ELISpot assay and LDH release assay. The therapeutic and tumor challenge assay were also examined. The results showed that the immune responses against MAGE-1 expressing murine tumors elicited by NE(MHS) via 4 different routes were approximately similar and were all stronger than that elicited by PBS or NE(-), suggesting that this novel nanoemulsion carrier can exert potent antitumor immunity against antigens encapsulated in it. Especially, the present results indicated that nanoemulsion vaccine adapted to administration via different routes including peroral, and may have broader applications in the future.
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PMID:The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following different administration routes. 1972 73

Methoxy poly(ethylene glycol)-block-oligo(l-aspartic acid)-block-poly(epsilon-caprolactone) with four aspartic acid groups was synthesized with a molecular weight and M(w)/M(n) of 8930 and 1.22. Polymeric micelles were formed by dialysis and stabilized by electrostatic interactions between the carboxylic acid groups and calcium cations. The critical micelle concentration of mPEG-Asp-PCL was determined to be 0.078 mg/mL. At 0.02 mg/mL, the dissociation of micelles without ionic stabilization formed an opaque, phase-separated solution, while the stabilized micelles under the same conditions showed structural stability through ionic stabilization. The paclitaxel-loading and efficiency were 8.7% and 47.6%, respectively, and the drug loading increased the mean diameter from 73.0 nm to 87 nm, which was increased further to 96 nm after ionic fixation. Rapid releases of approximately 65% of the encapsulated paclitaxel from a non-stabilized micelle and 45% from a stabilized micelle were observed in the first 24h at pH 7.4 in a PBS solution containing 0.1 wt% Tween 80. The stabilized micelles then showed a sustained, slow release pattern over a couple of weeks, while the profile from the non-stabilized micelles reached a plateau at approximately 75% after 50h. The enhanced micelle stability independent of concentration through ionic stabilization opens a way for preparing long circulating delivery systems encapsulating water-insoluble drugs.
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PMID:Stabilized polymeric micelles by electrostatic interactions for drug delivery system. 1973 30

The objective of this study was to improve the efficacy of polycaprolactone/bioglass (PCL/BG) bone substitute using demineralized bone matrix (DBM) or calcium sulfate (CS) as a third component. Composite discs involving either DBM or CS were prepared by compression moulding. Bioactivity of discs was evaluated by energy dispersive X-ray spectroscopy (ESCA) and scanning electron microscopy (SEM) following simulated body fluid incubation. The closest Calcium/Phosphate ratio to that of hydroxyl carbonate apatite crystals was observed for PCL/ BG/DBM group (1.53) after 15 day incubation. Addition of fillers increased microhardness and compressive modulus of discs. However, after 4 and 6-week PBS incubations, PCL/BG/DBM discs showed significant decrease in modulus (from 266.23 to 54.04 and 33.45 MPa, respectively) in parallel with its highest water uptakes (36.3 and 34.7%). Discs preserved their integrity with only considerable weight loss (7.5-14.5%) in PCL/BG/DBM group. In vitro cytotoxicity tests showed that all discs were biocompatible.
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PMID:In vitro and in vivo evaluation of the effects of demineralized bone matrix or calcium sulfate addition to polycaprolactone-bioglass composites. 1975 68

The epidermal growth factor receptor variant III (EGFRvIII) is the most common variation of EGFR. Because it shows a high frequency in several different types of tumor and has not been detected in normal tissues, it is an ideal target for tumor specific therapy. In this study, we prepared EGFRvIII-HBcAg fusion protein. After immunization with fusion protein, HBcAg or PBS, the titers of antibody in BALB/c mice immunized with fusion protein reached 2.75 x 10(5). Western blot analysis demonstrated that the fusion protein had specific antigenicity against anti-EGFRvIII antibody. Further observation showed fusion protein induced a high frequency of IFN-gamma-secreting lymphocytes. CD4+T cells rather than CD8+T cells were associated with the production of IFN-gamma. Using Renca-vIII(+) cell as specific stimulator, we observed remarkable cytotoxic activity in splenocytes from mice immunized with fusion protein. Mice were challenged with Renca-vIII(+) cells after five times immunization. In fusion protein group, three of ten mice failed to develop tumor and all survived at the end of the research. The weight of tumors in fusion protein were obviously lighter than that in other two groups (t = 4.73, P = 0.044; t = 6.89, P = 0.040). These findings demonstrated that EGFRvIII-HBcAg fusion protein triggered protective responses against tumor expressing EGFRvIII.
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PMID:Generation of fusion protein EGFRvIII-HBcAg and its anti-tumor effect in vivo. 1978 47


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