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Thediscovery of a new series of compounds that are potent, selective5-HT2Creceptor agonists is described herein as we continueour efforts to optimize the 2-phenylcyclopropylmethylamine scaffold.Modifications focused on the alkoxyl substituent present on the aromaticring led to the identification of improved ligands with better potencyat the 5-HT2Creceptor and excellent selectivity againstthe 5-HT2Aand 5-HT2Breceptors. ADMET studiescoupled with a behavioral test using the amphetamine-induced hyperactivitymodel identified four compounds possessing drug-like profiles andhaving antipsychotic properties. Compound (+)-16b, whichdisplayed an EC50of 4.2 nM at 5-HT2C, no activityat 5-HT2B, and an 89-fold selectivity against 5-HT2A, is one of the most potent and selective 5-HT2Cagonists reported to date. The likely binding mode of this seriesof compounds to the 5-HT2Creceptor was also investigatedin a modeling study, using optimized models incorporating the structuresof β2-adrenergic receptor and 5-HT2Breceptor. [ABSTRACT FROM AUTHOR]

This review provides an overview of smart chemistry developed and utilized in the last 5-10 years in polymer-based drug delivery nanomedicine. Smart chemistry not only facilitates the controlled drug loading in a highly specific manner, but also potentially controls the drug release kinetics at the targeted tissues. This review highlights the emergence of new chemistry or unique utilization of conventional chemistry in drug delivery, which is believed to play an important role in developing next generation nanomedicine. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the good effects of flavonoids from scutellaria baicalensis georgi on neuron dysfunction, memory, and metabolite disruption after cerebral ischemia/reperfusion in rats. It mentions that 32 Sprague-Dawley rats were randomly selected to establish the model of cerebral ischemia/reperfusion. It shows that such flavonoids have beneficial effects on ischemic brain disease treatment.

The accuracy of most of the existing semisupervised clustering algorithms based on small size of labeled dataset is low when dealing with multidensity and imbalanced datasets, and labeling data is quite expensive and time consuming in many real-world applications. This paper focuses on active data selection and semisupervised clustering algorithm in multidensity and imbalanced datasets and proposes an active semisupervised clustering algorithm. The proposed algorithm uses an active mechanism for data selection to minimize the amount of labeled data, and it utilizes multithreshold to expand labeled datasets on multidensity and imbalanced datasets. Three standard datasets and one synthetic dataset are used to demonstrate the proposed algorithm, and the experimental results show that the proposed semisupervised clustering algorithm has a higher accuracy and a more stable performance in comparison to other clustering and semisupervised clustering algorithms, especially when the datasets are multidensity and imbalanced. [ABSTRACT FROM AUTHOR]

A glue stick is comprised of solidified adhesive mounted in a lipstick-like push-up tube. Whey is a byproduct of cheese making. Direct disposal of whey can cause environmental pollution. The objective of this study was to use whey protein isolate (WPI) as a natural polymer along with polyvinylpyrrolidone (PVP) to develop safe glue sticks. Pre-dissolved WPI solution, PVP, sucrose, 1,2-propanediol (PG), sodium stearate, defoamer, and preservative were mixed and dissolved in water at 90 °C and then molded in push-up tubes. Chemical composition, functional properties (bonding strength, glue setting time, gel hardness, extension/retraction, and spreading properties), microstructure, and storage stability of the prototypes were evaluated in comparison with a commercial control. Results showed that all WPI/PVP prototypes had desirable bonding strength and exhibited faster setting than PVP prototypes and control. WPI could reduce gel hardness and form less compact and rougher structures than that of PVP, but there was no difference in bonding strength. PVP and sucrose could increase the hygroscopicity of glue sticks, thus increasing storage stability. Finally, the optimized prototype GS3 (major components: WPI 8.0%, PVP 12.0%, 1,2-propanediol 10.0%, sucrose 10.0%, and stearic sodium 7.0%) had a comparable functionality to the commercial control. Results indicated that whey protein could be used as an adhesive polymer for glue stick formulations, which could be used to bond fiber or cellulose derived substrates such as paper. [ABSTRACT FROM AUTHOR]

We encapsulated cyclosporine A (CsA) in poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PEG-PLGA) nanoparticles (NPs) by nanoprecipitation of CsA and PEG-PLGA. The resulting CsA/PEG-PLGA-NPs were <100nm in diameter with a narrow particle size distribution. The NP size could be controlled by tuning the polymer concentration, solvent, or water/solvent ratio during formulation. The PEGylated NPs maintained non-aggregated in salt solution. Solid NPs lyoprotected with bovine serum albumin were prepared for the convenience of storage and transportation. The release kinetics of CsA (55.6% released on Day 1) showed potential for maintaining therapeutic CsA concentrations in vivo. In T-cell assays, both free CsA and CsA/PEG-PLGA-NPs suppressed T-cell proliferation and production of inflammatory cytokines dose dependently. In a mixed lymphocyte reaction assay, the IC50 values for free CsA and CsA/PEG-PLGA-NPs were found to be 30 and 35 ng/mL, respectively. This nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and potentially reduced toxicity. [ABSTRACT FROM AUTHOR]

Cell-penetrating peptides (CPPs), such as the HIV TAT peptide, are able to translocate across cellular membranes efficiently. A number of mechanisms, from direct entry to various endocytotic mechanisms (both receptor independent and receptor dependent), have been observed but how these specific amino acid sequences accomplish these effects is unknown. We show how CPP sequences can multiplex interactions with the membrane, the actin cytoskeleton, and cell-surface receptors to facilitate different translocation pathways under different conditions. Using "nunchuck" CPPs, we demonstrate that CPPs permeabilize membranes by generating topologically active saddle-splay ("negative Gaussian") membrane curvature through multidentate hydrogen bonding of lipid head groups. This requirement for negative Gaussian curvature constrains but underdetermines the amino acid content of CPPs. We observe that in most CPP sequences decreasing arginine content is offset by a simultaneous increase in lysine and hydrophobic content. Moreover, by densely organizing cationic residues while satisfying the above constraint, TAT peptide is able to combine cytoskeletal remodeling activity with membrane translocation activity. We show that the TAT peptide can induce structural changes reminiscent of macropinocytosis in actin-encapsulated giant vesicles without receptors. [ABSTRACT FROM AUTHOR]

The article presents a study on the use of flavonoids from leaves and stems of scutellaria baicalensis georgi (SSF) in weakening H2N2 oxidative damage of cortical neurons on rats. The study uses methods such as estimation of malondialdehyde (MDA) assays using thiobarbituric acid method, primary culture on cortical neurons. Results show the role of flavonoids in reducing the injuries on cortical neurons, and its protection against superoxide dismutase (SOD).

Polymeric nanoparticles (NPs), prepared via coprecipitation of drugs and polymers, are promising drug delivery vehicles for treating diseases with improved efficacy and reduced toxicity. Here, we report an unprecedented strategy for preparing polylactide-cyclosporine A (PLA-CsA) NPs (termed CsA-NPs) through CsA-initiated ring-opening polymerization of lactide (LA) followed by nanoprecipitation. The resulting CsA-NPs have sub-100 nm sizes and narrow particle size distributions, and release CsA in a sustained manner without a "burst"-release effect. Both free CsA and CsA-NPs displayed comparable suppression of T-cell proliferation and production of inflammatory cytokines in various T-cell assays in a dose-dependent manner. The IC50 values for CsA and CsA-NPs were 27.5 and 72.0 ng/ml, respectively. As lymph nodes are the main loci for T-cell activation, we coupled dendritic cells (DCs) with CsA-NPs and successfully delivered CsA selectively to the lymph nodes. Our studies indicated that CsA-NPs could be internalized in the DCs with a sustained release of CsA to the culture medium, suppressing alloreactive T-cell proliferation. Allogeneic DCs loaded with CsA-NPs were able to migrate to the draining lymph nodes where the T-cell priming was significantly reduced without any systemic release. This innovative nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and reduced toxicity. [ABSTRACT FROM AUTHOR]

Tumor metastases occur through both the cardiovascular and lymphatic circulations. However, the majority of nanoparticle biodistribution studies have been focused on the cardiovascular circulation. In this study, we report the formulation of Cy5-labeled polylactide (Cy5-PLA) nanoparticles with controlled size and surface features and the subsequent evaluation of their lymphatic biodistribution. Cy5-PLA nanoparticles were formulated through Cy5/(BDI)ZnN(TMS)2-mediated [(BDI) 5 2-((2,6-diisopropylphenyl) amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene] ring-opening polymerization of lactide followed by nanoprecipitation. Their lymphatic biodistribution was evaluated by using whole-body fluorescence imaging of nude mice and ex vivo fluorescence imaging of the resected organs. This technique has the potential for providing optical contrast and drug delivery through the lymphatic circulation for the treatment of metastatic cancer. [ABSTRACT FROM AUTHOR]

In contrast to animal ferritin, relatively little information is available on phytoferritin. Black bean (Phaseolus vulgaris L.) has been consumed in many countries. In the present study, new ferritin from black bean seed was purified by two consecutive anion exchange and size exclusion chromatography. The apparent molecular mass of the native black bean seed ferritin (BSF) was found to be ∼560 kDa by native PAGE analysis. N-terminal sequence, MALDI-TOF-MS and MS/MS analyses indicate that BSF and soybean seed ferritin (SSF) share very high identity in amino acid sequence. However, SDS–PAGE result indicates that BSF consists of 26.5 (H-1) and 28.0 kDa (H-2) subunits with a ratio of 2 : 1, while the ratio of these two subunits in SSF is 1 : 1. This result demonstrates that the two proteins have different subunit composition which might affect their activities in iron uptake and release. Indeed, at high iron flux, the initial rate of iron oxidative deposition in apoBSF is larger than that in apoSSF. On the contrary, the iron release from BSF is significantly slower than that from SSF. All these results indicate that phytoferritin might regulate the transit of iron into and out of the protein cavity by changing its subunit composition. [ABSTRACT FROM PUBLISHER]

There are a number of challenges associated with designing nanoparticles for medical applications. We define two challenges here: (i) conventional targeting against up-regulated cell surface antigens is limited by heterogeneity in expression, and (ii) previous studies suggest that the optimal size of nanoparticles designed for systemic delivery is approximately 50-150 nm, yet this size range confers a high surface area-to-volume ratio, which results in fast diffusive drug release. Here, we achieve spatial control by biopanning a phage library to discover materials that target abundant vascular antigens exposed in disease. Next, we achieve temporal control by designing 60-nm hybrid nanoparticles with a lipid shell interface surrounding a polymer core, which is loaded with slow-eluting conjugates of paclitaxel for controlled ester hydrolysis and drug release over approximately 12 days. The nanoparticles inhibited human aortic smooth muscle cell proliferation in vitro and showed greater in vivo vascular retention during percutaneous angioplasty over nontargeted controls. This nanoparticle technology may potentially be used toward the treatment of injured vasculature, a clinical problem of primary importance. [ABSTRACT FROM AUTHOR]

We report here a unique method for formulating doxorubicin-polylactide (Doxo-PLA) conjugate nanoparticles, known as nanoconjugates (NCs), through Doxo/(BDI)ZnN(TMS)2-mediated [(BDI) = 2-((2,6- diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene], chemo- and regioselective polymenzations of lactide (LA) followed by nanoprecipitation. When Doxo/(BDI)ZnN(TMS)2 was mixed with 1-pyrenemethanol (Pyr-OH) and 1-pyrenemethylamine (Pyr-NH2) and the mixture was utilized for the polymerization of LA, remarkable chemoselectivity was observed. Pyr-OH was completely consumed and covalently linked to the terminus of the PLA, whereas the Pyr-NH2 remained intact in the polymerization solution. When Doxo was used as the initiator to polymerize LA in the presence of (BDI)ZnN(TMS)2, the polymerization was complete within hours, with nearly 100% Doxo-loading efficiency and 100% LA conversion. Doxo loading as high as 27% could be achieved at a LA/Doxo ratio of 10. Both the steric bulk of the chelating ligand and the metal catalyst had dramatic effects on the regioselectivity during the initiation step. When Doxo/(BDI)ZnN(TMS)2 was mixed with succinic anhydride (SA) to mimic the initiation of Doxo/(BDI)ZnN(TMS)2-mediated LA polymerization, Doxo- 14-succinic ester (Doxo-SE) was the predominate product. When the steric bulk of BDI was reduced or when the BDI ligand was removed, significant amounts of Doxo-4′, 1 4-bis-succinic ester (Doxo-2SE) and Doxo-4′,9,14- trisuccinic ester (Doxo-3SE) were formed. The use of (BDI)MgN(TMS)2 in such a reaction also resulted in reduced regioselectivity and formation of both Doxo-SE and Doxo-2SE. Doxo/(BDI)ZnN(TMS)2-mediated LA polymerizations yielded Doxo-PLA conjugates with well-controlled molecular weights and polydispersities (as low as 1.02). The nanoprecipitation of Doxo-PLA formed NCs less than 150 nm in size with narrow particle size distributions. The sustained release of Doxo from Doxo-PLA NCs was achieved without a burst release. This method may have widespread utility for controlled conjugation of hydroxyl-containing agents to polyesters and formation of corresponding nanoparticles. [ABSTRACT FROM AUTHOR]

Directed differentiation of embryonic stem (ES) cells is useful for creating models of human disease and could potentially generate a wide array of functional cell types for therapeutic applications. Methods to differentiate ES cells often involve the formation of cell aggregates called embryoid bodies (EBs), which recapitulate early stages of embryonic development. EBs are typically made from suspension cultures, resulting in heterogeneous structures with a wide range of sizes and shapes, which may influence differentiation. Here, we use microfabricated cell-repellant poly(ethylene glycol) (PEG) wells as templates to initiate the formation of homogenous EBs. ES cell aggregates were formed with controlled sizes and shapes defined by the geometry of the microwells. EBs generated in this manner remained viable and maintained their size and shape within the microwells relative to their suspension counterparts. Intact EBs could be easily retrieved from the microwells with high viability (>95%). These results suggest that the microwell technique could be a useful approach for in vitro studies involving ES cells and, more specifically, for initiating the differentiation of EBs of greater uniformity based on controlled microenvironments. [ABSTRACT FROM AUTHOR]

The kinetics of thermal degradation of poly (p‐phenylen benzobisoxazole) (PBO) were studied by thermogravimetric analysis (TG) in dynamic nitrogen gas at four different heating rates: 5, 10, 15, 20°C/min. The activation energy calculated by Kissinger Method was 352.19 kJ/mol, and the mean value of activation energies evaluated by Flynn‐Wall‐Ozawa Method was 338.32 kJ/mol. The degradation kinetic model of PBO followed the mechanism of random scission of weak bonds of PBO molecule and impact of the active groups obtained from the broken bonds, Mampel Power equation with integral form G(α) = α3/2 and differential form$ f(\alpha)={2\over 3}\alpha^{-1/2} $. And the mathematical equation of kinetic compensation effect was ln A = 0.1365 Ea − 1.4102. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3675–3679, 2007 [ABSTRACT FROM AUTHOR]

Purpose: IT-101 is a camptothecin–polymer conjugate prepared by linking camptothecin (CPT) to a hydrophilic, cyclodextrin-based, linear polymer through ester bonds. In previous studies, these polymer conjugates with high molecular weights (ca 90 kDa) have shown significant antitumor effects against human colon carcinoma xenografts. The pharmacokinetics of IT-101 in plasma of rats and its biodistribution in nude mice bearing human LS174T colon carcinoma tumors is reported here. Methods: Sprague–Dawley rats were injected intravenously with three different doses of IT-101. Serial plasma samples were analyzed for polymer-bound and unconjugated CPT by high-performance liquid chromatography (HPLC). Concentration vs time data were modeled using non-compartmentalized methods and compared to CPT alone injected intravenously at an equivalent dose. Tumor-bearing mice were injected intravenously with IT-101 and intraperitoneally with CPT alone, and sacrificed after 24 and 48 h, and serum, heart, liver, spleen, lungs and tumor collected. Tissue samples were extracted and analyzed for polymer-bound and unconjugated CPT by HPLC. Results: Plasma concentrations and the area under the curve for polymer-bound CPT are approximately 100-fold higher than those of unconjugated CPT or CPT alone, injected intravenously at an equivalent dose. The plasma half-life of IT-101 ranges from 17 -20 h and is significantly greater than that of CPT alone (1.3 h). When CPT is conjugated to polymer, the biodistribution pattern of CPT is different from that taken alone. At 24 h post injection, the total CPT per gram of tissue is the highest in tumor tissue when compared to all other tissues tested. Tumor concentrations of active CPT released from the conjugate are more than 160-fold higher when administered as a polymer conjugate rather than as CPT alone. Conclusions: The studies presented here indicate that intravenous administration of IT-101, a cyclodextrin based polymer–CPT conjugate, gives prolonged plasma half-life and enhanced distribution to tumor tissue when compared to CPT alone. The data also show that active CPT is released from the conjugate within the tumor for an extended period of time. These effects likely play a significant role in the enhanced antitumor activity of IT-101 when compared to CPT alone or irinotecan. [ABSTRACT FROM AUTHOR]

Targeted uptake of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology. Using prostate cancer as a model, we report docetaxel (Dtxl)-encapsulated nanoparticles formulated with biocompatible and biodegradable poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) copolymer and surface functionalized with the A10 2'-fluoropyrimidine RNA aptamers that recognize the extracellular domain of the prostate-specific membrane antigen (PSMA), a well characterized antigen expressed on the surface of prostate cancer cells. These Dtxl-encapsulated nanoparticle-aptamer bioconjugates (Dtxl-NP-Apt) bind to the PSMA protein expressed on the surface of LNCaP prostate epithelial cells and get taken up by these cells resulting in significantly enhanced in vitro cellular toxicity as compared with nontargeted nanoparticles that lack the PSMA aptamer (Dtxl-NP) (P < 0.0004). The Dtxl-NP-Apt bioconjugates also exhibit remarkable efficacy and reduced toxicity as measured by mean body weight loss (BWL) in vivo [body weight loss of 7.7 ± 4% vs. 18 ± 5% for Dtxl-NP-Apt vs. Dtxl-NP at nadir, respectively (mean ± SD); n = 7]. After a single intratumoral injection of Dtxl-NP-Apt bioconjugates, complete tumor reduction was observed in five of seven LNCaP xenograft nude mice (initial tumor volume of ≈300 mm³), and 100% of these animals survived our 109-day study. In contrast, two of seven mice in the Dtxl-NP group had complete tumor reduction with 109-day survivability of only 57%. Dtxl alone had a survivability of only 14%. Saline and nanoparticles without drug were similarly nonefficacious. This report demonstrates the potential utility of nanoparticle-aptamer bioconjugates for a therapeutic application. [ABSTRACT FROM AUTHOR]

The article reports on the unusual finding of controlled, living polymerizations of N-carboxy-anhydrides (NCAs) mediated by hexameth-yldisilazane (HMDS) and the identification of trimethylsilyl carbamate (TMS-CBM). It is determined that the HMDS-mediated NCA polymerizations correspond to some extent the group transfer polymerizations (GTPs) of acrylic monomers initiated by similar organosilicon compounds.

Inhibition of overexpressed enzymes is among the most promising approaches for tar)geted cancer treatment. However, many cancer-expressed enzymes are “nonlethal,” in that the inhibition of the enzymes’ activity is insufficient to kill cancer cells. Conventional antibody-based therapeutics can mediate efficient treatment by targeting extracellular nonlethal targets but can hardly target intracellular enzymes. Herein, we report a cancer targeting and treatment strategy to utilize intracellular nonlethal enzymes through a com)bination of selective cancer stem-like cell (CSC) labeling and Click chemistry-mediated drug delivery. A de novo designed compound, AAMCHO [N-(3,4,6-triacetyl)N-azidoacetylmannosamine)-cis-2-ethyl-3-formylacrylamideglycoside], selectively labeled cancer CSCs in vitro and in vivo through enzymatic oxidation by intracellular aldehyde dehydrogenase 1A1. Notably, azide labeling is more efficient in identifying tumorigenic cell populations than endogenous markers such as CD44. A dibenzocy)clooctyne (DBCO)-toxin conjugate, DBCO-MMAE (Monomethylauristatin E), could next target the labeled CSCs in vivo via bioorthogonal Click reaction to achieve excellent anticancer efficacy against a series of tumor models, including orthotopic xenograft, drug-resistant tumor, and lung metastasis with low toxicity. A 5/7 complete remission was observed after single-cycle treatment of an advanced triple-negative breast cancer xenograft (~500 mm³ ). [ABSTRACT FROM AUTHOR]

Controlled assembly of inorganic nanoparticles (NPs) into structurally defined supramolecular polymers will create nanomaterials with new collective properties. However, supramolecular polymerization of isotropic NPs remains a challenge because of the lack of anisotropic interactions in these monomers to undergo directional associations for the cooperative growth of supramolecular chains. Herein we report self-assembly behavior of poly(L-glutamic acid)-grafted gold NPs in solution and describe how combined attractive and repulsive interactions influence the shape and size of the resulting supramolecular assemblies. The study shows that the chain growth of supramolecular polymers can be achieved from the NP monomers and the process occurs in two distinct stages, with a slow nucleation step followed by a faster chain propagation step. The resulting supramolecular structures depend on both the grafting density of the poly(L-glutamic acid) on the NPs and the size of the NPs. [ABSTRACT FROM AUTHOR]

We report preclinical proof of principle for effective treatment of B-precursor acute lymphoblastic leukemia (ALL) by targeting the spleen tyrosine kinase (SYK)-dependent antiapoptotic blast cell survival machinery with a unique nanoscale pharmaceutical composition. This nanoscale liposomal formulation (NLF) contains the pentapeptide mimic 1 ,4-Bis (9-0 dihydroquinidinyl) phthalazine/hydroquinidine 1 ,4-phathalazinediyl diether (C61) as the first and only selective inhibitor of the substrate binding P-site of SYK. The C61 NLF exhibited a very favorable pharmacokinetic and safety profile in mice, induced apoptosis in primary B-precursor ALL blast cells taken directly from patients as well as in vivo clonogenic ALL xenograft cells, destroyed the in vivo clonogenic fraction of ALL blast cells, and, at nontoxic dose levels, exhibited potent in vivo antileukemic activity against patient-derived ALL cells in xenograft models of aggressive B-precursor ALL. Our findings establish SYK as an attractive molecular target for therapy of B-precursor ALL. Further development of the C61 NLF may provide the foundation for therapeutic innovation against therapy- refractory B-precursor ALL. [ABSTRACT FROM AUTHOR]

Integrated circuits (ICs) must be robust to manufacturing variations. Circuit simulation at a set of worst case corners is a computationally efficient method for verifying the robustness of a design. This paper presents a new statistical methodology to determine the worst case corners for a set of circuit performances. The proposed methodology first estimates response surfaces for circuit performances as quadratic functions of the process parameters with known statistical distributions. These response surfaces are then used to extract the worst case. corners in the process parameter space as the points where the circuit performances are at their minimum/maximum values corresponding to a specified tolerance level. Corners in the process parameter space close to each other are clustered to reduce their number, which reduces the number of simulations required for design verification. The novel concept of a relaxation coefficient to ensure that the corners capture the minimum/maximum values of all the circuit performances at the desired tolerance level is also introduced. The corners are realistic since they are derived from the multivariate statistical distribution of the process parameters at the desired tolerance level. The methodology is demonstrated with examples showing extraction of corners from digital standard cells and also the corners for analog/radio frequency (RF) blocks found in typical communication ICs. [ABSTRACT FROM AUTHOR]

Nanoparticles and microparticles have many potential biomedical applications ranging from imaging to drug delivery. Therefore, in vitro systems that can analyze and optimize the interaction of such particles with cells may be beneficial. Here, we report a microfluidic system that can be used to study these interactions. As a model system, we evaluated the interaction of polymeric nanoparticles and microparticles and similar particles conjugated to aptamers that recognize the transmembrane prostate specific membrane antigen (PSMA), with cells seeded in microchannels. The binding of particles to cells that expressed or did not express the PSMA (LNCaP or PC3, respectively) were evaluated with respect to changes in fluid shear stress, PSMA expression on target cells, and particle size. Nanoparticle-aptamer bioconjugates selectively adhered to LNCaP but not PC3 cells at static and low shear (<1 dyn/cm²) but not higher shear (∼4.5 dyn/cm²) conditions. Control nanoparticles and microparticles lacking aptamers and microparticle-aptamer bioconju gates did not adhere to LNCaP cells, even under very low shear conditions (∼0.28 dyn/cm²). These results demonstrate that the interaction of particles with cells can be studied under controlled conditions, which may aid in the engineering of desired particle characteristics. The scalability, low cost, reproducibility, and high-throughput capability of this technology is potentially beneficial to examining and optimizing a wide array of cell-particle systems prior to in vivo experiments. [ABSTRACT FROM AUTHOR]

The article reports on the use of controlled polymerization techniques in preparing and synthesizing of brush-like polymers. The techniques include the integrated ring-opening metathesis polymerization (ROMP) and polymerization of amino acid N-Carboxyanhydrides. The strategies are specifically designed in accordance to how polymers behave.

Background: Macrophages are heterogenous phagocytic cells with an important role in the innate immunity. They are, also, significant contributors in the adaptive immune system. Macrophages are the most abundant immune cells in the lung during allergic asthma, which is the most common chronic respiratory disease of both adults and children. Macrophages activated by Th1 cells are known as M1 macrophages while those activated by IL-4 and IL-13 are called alternatively activated macrophages (AAM) or M2 cells. AAM are subdivided into four distinct subtypes (M2a, M2b, M2c and M2d), depending on the nature of inducing agent and the expressed markers. BODY: IL-4 is the major effector cytokine in both alternative activation of macrophages and pathogenesis of asthma. Thus, the role of M2a macrophages in asthma is a major concern. However, this is controversial. Therefore, further studies are required to improve our knowledge about the role of IL-4-induced macrophages in allergic asthma, through precisive elucidation of the roles of specific M2a proteins in the pathogenesis of asthma. In the current review, we try to illustrate the different functions of M2a macrophages (protective and pathogenic roles) in the pathogenesis of asthma, including explanation of how different M2a proteins and markers act during the pathogenesis of allergic asthma. These include surface markers, enzymes, secreted proteins, chemokines, cytokines, signal transduction proteins and transcription factors., Conclusions: AAM is considered a double-edged sword in allergic asthma. Finally, we recommend further studies that focus on increased selective expression or suppression of protective and pathogenic M2a markers.

Alzheimer's disease (AD) is an irreversible, progressive brain disease that slowly destroys memory and is accompanied by neuron loss and structure change. With the increase of AD patients worldwide, the pathology and treatment of the disease has become a focus in the International Pharmaceutical Industry. Thus, the establishment of the animal model to mimic AD in the laboratory is of great importance. Here, we describe a detailed protocol for establishing a mimic of AD in a rat animal model though intracerebroventricular injection of amyloid beta protein 25-35 (Aβ25-35) combined with aluminum trichloride (AlCl3) and anterodorsal thalamic nucleus injection of recombinant human transforming growth factor-β1 (RHTGF-β1) to rats. The related markers of AD were measured, including: spatial memory, neuronal structure and substructure, neuronal Aβ, and neurofibrillary tangles (NFT) production. This rat model demonstrates spatial memory impairment, neuronal structure and substructure pathological changes, neuron intracellular Aβ burden, and NFT aggregation, and provides a close mimic of the neuronal structure and function disorder to that of clinical AD patients. Thus, the presented AD rat modelprovides a valuable in vivo tool for exploring neuronal function, neuronal pathology, and drug screening of AD.