Low Weight Molecules Research Articles

Polymeric stent materials dysregulate macrophage and endothelial cell functions: Implications for coronary artery stent

BackgroundBiodegradable polymers have been applied as bulk or coating materials for coronary artery stents. The degradation of polymers, however, could induce endothelial dysfunction and aggravate neointimal formation. Here we use polymeric microparticles to simulate and demonstrate the effects of degraded stent materials on phagocytic activity, cell death and dysfunction of macrophages and endothelial cells. MethodsMicroparticles made of low molecular weight polyesters were incubated with human macrophages and coronary artery endothelial cells (ECs). Microparticle-induced phagocytosis, cytotoxicity, apoptosis, cytokine release and surface marker expression were determined by immunostaining or ELISA. Elastase expression was analyzed by ELISA and the elastase-mediated polymer degradation was assessed by mass spectrometry. ResultsWe demonstrated that poly(D,L-lactic acid) (PLLA) and polycaprolactone (PCL) microparticles induced cytotoxicity in macrophages and ECs, partially through cell apoptosis. The particle treatment alleviated EC phagocytosis, as opposed to macrophages, but enhanced the expression of vascular cell adhesion molecule (VCAM)-1 along with decreased nitric oxide production, indicating that ECs were activated and lost their capacity to maintain homeostasis. The activation of both cell types induced the release of elastase or elastase-like protease, which further accelerated polymer degradation. ConclusionsThis study revealed that low molecule weight PLLA and PCL microparticles increased cytotoxicity and dysregulated endothelial cell function, which in turn enhanced elastase release and polymer degradation. These indicate that polymer or polymer-coated stents impose a risk of endothelial dysfunction after deployment which can potentially lead to delayed endothelialization, neointimal hyperplasia and late thrombosis.

Iminodiacetic acid functionalized porous hydroxyapatite nanoparticles for capturing histidine-tagged proteins

A simple strategy has been developed to synthesize hydroxyapatite (HAP) nanoparticles (NPs) in a simulated body fluid (SBF). The HAP NPs have an average diameter of 50nm and present porous structure. By taking advantage of surface hydroxyl groups, the HAP NPs are further modified with iminodiacetic acid (IDA), followed by chelating Ni2+ ions. The HAP/IDA-Ni2+ NPs as novel adsorbent can capture directly histidine-tagged (His-tagged) proteins from the mixture of lysed cells without sample pretreatment. Results indicated that the HAP/IDA-Ni2+ NPs present negligible nonspecific adsorption and high protein binding ability, and their specificity and affinity toward His-tagged proteins can remain after 5 times of recycling. The HAP/IDA-Ni2+ NPs are especially suitable for purification of His-tagged proteins with low molecule weight.

Pure magnetic hard fct FePt nanoparticles: Chemical synthesis, structural and magnetic properties correlations

FePt nanoparticles, containing a near-equal atomic percentage of Fe and Pt, with a face centered tetragonal structure (fct), are challenging for potential applications in high performance permanent magnets and high density data storage. In this study, we report on the chemical synthesis, carried out both solvothermally and hydrothermally in autoclave reacting iron (III) acetylacetonate and platinum (II) acetylacetonate with tri- or tetra-ethylene glycol, these employed as solvents, reducers and particle surface protecting agents as well. In both methods, a subsequent thermal treatment at high temperatures is necessary to transform the magnetic soft face centered cubic (fcc) phase to the hard fct one. Organic low-weight molecules, generally used to protect the nanoparticle surface and avoid particle aggregation, are decomposed by the thermal treatment resulting in particle aggregation and coalescence phenomena; on the contrary, in this case, a polymer matrix is formed as particle protecting agent and, by thermally treating the hydrothermally prepared nanoparticles up to 750 °C for 1 h, the pure magnetic hard fct phase is obtained while preserving the nanostructure. A detailed study is carried out on FePt nanoparticle structure (fcc and fct phases) and correlated to the magnetic properties of the system.

Aspects of soil phenolic matter (SPM): An explorative investigation in agricultural, agroforestry, and wood ecosystems

This paper assesses the distribution of soil phenolic matter (SPM) in soil environments from a pedological perspective, with particular emphasis on soil horizonation and its involvement in pedogenic processes.The study was conducted on 15 soil profiles (Andosols, Calcisols, Cambisols, Lixisols, Phaeozems, Podzols, Umbrisols) covering five distinct ecosystems. Although the ecosystems were virtually homogeneous in and of themselves, they represented strongly contrasting climates, geolithology and morphology, land use and vegetation cover (intensive agriculture, chestnut grove, alpine pasture, woody reforestations, and natural woods). Three main SPM fractions were categorised: (i) “total” (SPMt), (ii) “soluble” and/or “labile” (SPMs), and (iii) the fraction with a “high” (SPMh) affinity for the soil body.The SPMh and SPMs contents varied significantly, averaging 2.84±0.52gkg−1 and 0.07±0.02gkg−1, respectively. Thus, these fractions appear to belong to different soil organic matter (SOM) pools. Indeed, the SPMs fraction was characterised by transitional, ephemeral low-weight molecules, which continuously reached the soil through both plant metabolism/decay and SOM degradation and were subsequently transformed into larger materials (humic matter, organo-mineral complexes) and/or lost by leaching and mineralisation. The SPMh fraction is likely involved in pedogenic processes that are primarily driven by the transport/translocation of colloidal phases under the following conditions: (i) in the early stages of horizon differentiation or, more specifically, in transport processes from the overlying A horizons and (ii) in cheluviation phenomena leading to the formation of spodic horizons. Moreover, SPMh also appears to be involved in early “in situ” alteration of cambic horizons. This involvement may result from the strong etching/complexing activity of soluble polyphenols from the overlying horizon, which promotes “in situ” weathering of the parent material.The total amount of SPM in a given environment greatly depended on the environmental conditions, which ranged from 0.02gkg−1 in an intensively cultivated Haplic Cambisol to 13.14gkg−1 in an Andic Cambisol under natural downy oak cover. Additionally, the SPMh/SPMs and SPMt/SOM% ratios decreased significantly from natural woods to intensive agriculture systems and may therefore indicate the extent of different anthropic impacts, such as soil cover/land use, in different ecosystems.

Biodegradable and amphiphilic block copolymer–doxorubicin conjugate as polymeric nanoscale drug delivery vehicle for breast cancer therapy

Polymeric nanoparticles have shown great promise as attractive vehicles for drug delivery. In this study, we designed, prepared and characterized biodegradable amphiphilic triblock HPMA copolymer–doxorubicin (copolymer–DOX) conjugate based nanoparticle as enzyme-sensitive drug delivery vehicle. The enzyme-sensitive peptide GFLGKGLFG was introduced to the main chain of the copolymer with hydrophilic and hydrophobic blocks. The triblock HPMA polymer–DOX conjugate with high molecules (Mw 90 kDa) can be degraded to product with low molecule weight (Mw 44 kDa) below the renal threshold. The copolymer–DOX conjugate can self-assemble into compact nanoparticle, which was characterized by scanning electron microscope (SEM) and atomic force microscope (AFM) studies. This polymeric nanoparticle substantially enhanced antitumor efficacy compared to the free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis on the 4T1 murine breast cancer model confirmed by the evidences from mice weight shifts, tumor growth curves, tumor growth inhibition (TGI), immunohistochemical analysis and histological assessment. The in vivo toxicity evaluation demonstrated that the polymeric nanoparticle reduced DOX-induced toxicities and presented no significant side effects to normal organs of both tumor bearing and healthy mice as measured by body weight shift, blood routine test and histological analysis. Therefore, the triblock HPMA copolymer–DOX conjugate based nanoparticle is promising as a potential drug delivery vehicle for breast cancer therapy.

Intraoperative acute pulmonary embolism: risk factors, diagnosis and treatment

Background Understanding the risk factors of intraoperative acute pulmonary embolism(APE) is beneficial for the prompt diagnosis and treatment.Objective This review is to discuss the diagnosis and treatment,and the subsequent research of APE.Content This review restrospectively analyzes the risk factors,clinical presentation,diagnosis and treatment of the intraoperative APE in relevant articles and case reports.Trend The examination of transthoracic or transesophageal echocardiography during operation may provide a relatively reliable diagnosis of APE.Hypodermic injection of low molecule weight heparin for short-term anticoagulation and thrombectomy for patients with tumor thrombus may produce a relatively good therapeutic effect. Key words: Operation; Acute pulmonary embolism; Risk factors; Diagnosis; Treatment

THU0264 Efficacy and Safety of Cyclosporine-A During Pregnancy in Autoimmune Diseases

BackgroundCyclosporin-A (CYS-A) is an immunosuppressant agent widely used in the context of anti-rejection therapy. In Rheumatology it’s indicated for Rheumatoid Arthritis (RA) and Psoriasic Arthritis (PA), but it’s also administered...

Characterization of coagulation behavior of titanium tetrachloride coagulant for high and low molecule weight natural organic matter removal: The effect of second dosing

A two-stage titanium tetrachloride (TiCl4) dosing strategy is applied for investigating the coagulation effect on simulated water containing humic acid (HA) and fulvic acid (FA) and these represent the dissolved organic matter (DOM). The influence of second TiCl4 dose on coagulation efficiency, flock re-growth and the fractal dimension properties is studied for the beneficial effect of the second coagulant dose. Moreover, the impact of increased shear on the ultra filtration permeate flux in coagulation–ultra filtration (C–UF) hybrid process is explored. A small second dose essentially decreases the residual turbidity and improves the organic matter removal. Also, flocks with larger size and better recoverability result and having more compact structure than those obtained without the second TiCl4 coagulant dose. At the same total TiCl4 coagulant concentrations, the two-stage dosing mode reveals significant advantage over the single coagulant dosing in terms of turbidity removal, flock size and recoverability although organic matter removal and flock compactness degree are more or less deteriorated during the two-stage dosing process. The second TiCl4 dose contributes to larger re-generated flocks with better re-growth ability than those obtained without the second dose within a wide range of high shear rate and even with prolonged breaking period. Two-stage dosing mode could improve the ultra filtration permeate flux under certain shear conditions. An extension in breakage time leads to much severer flux decline than short breakage periods. In case of FA simulated water, the ultra filtration permeate flux was less sensitive to increasing shear rate than in case of HA simulated water.

High and low molecular weight hyaluronan use TSG-6 or CD44 signaling pathways respectively in activation of different subsets of dendritic cells thereby affecting the development of encephalitogenic T effector cells and autoimmune encephalomyelitis (P5172)

Abstract Microglia and astrocytes can overexpress hyaluronan in demyelinated lesion of brain in multiple sclerosis (MS), which affects the remyelination of axons. However, the exact role of hyaluronan in the development and treatment of MS is not clear. This becomes more complicated because the prototype hyaluronan is degraded into fragments of various sizes in MS. Previous studies using high molecule weight hyaluronan (HMW-HA) or low molecule weight hyaluronan (LMW-HA) have so far resulted in confusing or contradictory results. In this report, we found that HMW-HA and LMW-HA used different receptors depending on the subsets of dendritic cells (DC), which affect the activation of DC and subsequent development of effector T cells. HMW-HA (950KDa) bound to tumor necrosis factor-6 (TSG-6) receptor on myeloid DC (mDC) and induced a Th2 biased response. LMW-HA (12Kda) bound to CD44 receptors on plasmacytoid DC (pDC) and lymphoid DC (lDC) and induced a Th17 biased response. Accordingly, systemic administration of HMW-HA inhibited the development of experimental autoimmune encephalomyelitis (EAE), whereas systemic administration of LMW-HA exacerbated the development of EAE. We also found that gamma-interferon-inducible lysosomal thiol-reductase (GILT) was required for the therapeutic activity while HMW-HA and LMW-HA regulated GILT activity differentially. Our study, for the first time, elucidated the distinct role of hyaluronan in the development and treatment of MS.

Flow-injection methods for the determination of antioxidant activity based on free-radical processes

Flow-injection procedures are developed for the spectrophotometry determination of the antioxidant properties of low-weight biological molecules based on their interaction with free organic radicals, namely, the on-line generated radical cation from 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) and the longlived 2,2′-diphenyl-1-picrylhydrazyl radical. The optical and redox properties of these radicals in aqueous and water-ethanol media are studied with and without an antioxidant in the mixture. The applicability of the methods is demonstrated on a number of exogenous antioxidants: ascorbic and uric acid, glutathione, and others, trolox, a synthetic analogue of α-tocopherol, and species of plant origin: gallic, ferulic, and caffeic acids. The comparative evaluation of the total antioxidant activity of known anti-inflammatory medicines is performed. The throughput of the methods reported is 90–200 analyses per hour.

Structure and antioxidant activities of sulfated guar gum: Homogeneous reaction using DMAP/DCC catalyst

It was essential to understand the chemical structure of polysaccharides for further research and biochemical or medical application of this natural biopolymer. In the present study, sulfated derivatives of guar gum with high degree of sulfation (DS) were synthesized using 4-dimethylaminopyridine (DMAP)/dimethylcyclohexylcarbodiimide (DCC) as catalyst in homogeneous conditions. The effects of the ratio of chlorosulfuric acid to pyridine, the content of catalyst and reaction temperature were investigated. Results of FT-IR, 1H and 13C NMR indicated that C-6 substitution was predominant in sulfated polysaccharide. In the sulfation reaction, a sharp decrease in MW was observed. The enhanced antioxidant activities of sulfated polysaccharides were not a function of a single factor but a combination of high DS and low molecule weight.

RESPONSES OF SOME GRASS SPECIES TO DIESEL FUEL CONTAMINATED SOIL

Contamination of soil with petroleum products especially diesel fuel has been a major cause of concern. Automated gas oil (AGO) i.e. Diesel fuel is a complex mixture of petroleum hydrocarbons containing volatile, low molecule weight alkanes which are potentially phytotoxic, tonaphthalenes which may interfere with normal plant development. Two concentrations of diesel fuel namely 5g and 10g were used to contaminate soil. Thus six species of the family Poaceae namely Sorghum bicolor, Sorghum vulgare, Zea mays, Pennisetum glaucum, Phaseolus vulgaris and Triticum aestivum were used to phytoremediate the polluted soil. Phytoremediation is an innovative technology that uses plants to remove environmental contaminants in the growth substrate through physical, chemical or biological processes. Decrease in levels of diesel was accompanied by better germination and growth. Initially, seed germination was low as compared to control but it improved steadily in experimental plants. Among the six species studied, S. bicolor exhibited a moderate germination, plant height and leaf length at 5% and 10% diesel contaminations when compared to the control, thus it can be used for phytoremediation of diesel contaminated soils.

Effect of size-fractionated fish protein hydrolysate on growth and feed utilization of turbot (Scophthalmus maximusL.)

Four experimental diets were fed to turbot to examine the effect of fish hydrolysate and ultra-filtered fish hydrolysate on growth performance, feed utilization and non-specific immune response. Fish hydrolysate was produced by enzymatic treatment and size fractionated using ultra-filtration (UF). The permeate (molecular weight <1000 Da) after UF and the non-ultra-filtered fish hydrolysate (NUF) were tested as feed ingredients. Diets UF1, UF2 contained 3.7%, 1.2% ultra-filtered fish hydrolysate to replace fish meal protein respectively. The diets UF1, NUF were identical in composition except that the molecular weight of fish hydrolysate in the diet. Fish meal was used in the control diet. All diets were made equal in protein, lipid and energy. Each experimental diet was fed to juvenile turbot (27.87 ± 0.04 g) in triplicate for 8 weeks. Results of this study indicate that the best overall growth and feed utilization of turbot juveniles were obtained with a diet containing higher dose of the small molecular weight compounds in fish hydrolysate. Acid phosphatase, alkaline phosphatase, lysozyme and superoxide dismutase activity in serum were not affected by diet. Total antioxidant capacity was improved with increasing level of low molecule weight fish hydrolysate (UF1).

Solute effects on supercritical fluid

Supercritical carbon dioxide has been widely used as solvent, although its solubility is much lower than that of typical organic solvents in liquid state in general. Entrainer effects are known and utilised, in which adding low-weight molecules, such as alcohols (e.g. methanol and ethanol) and hydrocarbons (e.g. pentane and hexane), increases the solubility and the chemical reactivity. In this study, we investigated the change of local fluid structure and thermodynamic properties with molecular dynamics simulations, focusing on the entrainer effect. A monatomic fluid mixture model based on the Lennard-Jones model potential was adopted for simplicity; the parameters of which roughly correspond to those of carbon dioxide (solvent) and ethanol (solute). A series of simulations were performed in the vicinity of the gas–liquid critical point (CP). The radial distribution function and the coordination number reveal the enhancement of the solvent local density. The solvent chemical potential was evaluated with the Widom's particle insertion method. The chemical potential change by adding solutes is smallest in magnitude at the CP, qualitatively agreeing with recent experimental analysis and interpretation with a small-angle neutron scattering method.

TG-FTIR Analysis of Wood Based Bio-Oil

The combustion mechanism of bio-oil derived from wood fast pyrolysis was investigated by thermogravimetric analysis coupled with Fourier transform infrared spectroscopy (TG–FTIR) in flowing air. The results show that the combustion process of bio-oil consists of two main consecutive stages at a low heating rate. The combustion reaction becomes more and more intense from the first to the second stage. The release of volatiles occurs mainly at 80～200 °C and 350～500°C, and the gaseous products in each stage are different. The main products in the first stage are H2O with a few low molecule weight compounds, such as methanol, formic acid, etc. In the second stage, some new volatiles such as CO2, CO and CH4, etc. are present. Among the above volatiles, CO2 is the dominant gaseous product in the whole combustion process. The concentrations of CO2 and CO keep increasing, and reach the maximum at about 450 °C. Over 570°C, there are few products released at the end of the combustion process.

PH-dependent mode of antibacterial actions of low molecular weight water-soluble chitosan (LMWSC) against various pathogens

This study examined the antibacterial mode of action of low molecular weight water-soluble chitosan (LMWSC; MW1, MW3, MW5 and MW10) using a combination of approaches, including antibacterial assays, culture in media with different pH values, bactericidal kinetics, cellular leakage measurements, depolarization, and electron microscopy, as well as an in vivo study utilizing a wound infection and wound healing model. The antibacterial activity of LMWSC was related inversely to pH, with higher activities being observed at lower pH values. In addition, evaluation of the effect of bactericidal concentrations of LMWSC on the morphology of Bacillus megaterium and Escherichia coli O–157 revealed that it induces filamentation. Furthermore, the degree of depolarization (in Escherichia coli, pH 7.4) and calcein leakage (lipid composition; L-α-phosphatidylethanolamine (PE)/L-α-phosphatidyl-dl-glycerol (PG)=7/3 (w/w), pH 5.4 and 7.4) were evaluated. Moreover, cells cultured at various pHs were evaluated by confocal microscopy (pH 5.4 and 7.4). These results showed that treatment with LMWSC with different molecular weights had different effects on bacteria. In particular, LMWSC (MW10) cause more visible damage to the bacterial cell membrane than lower molecular weight LMWSC, which is due most likely to the penetration of cells by the lower weight molecules. Interestingly, MW5 was found to attack the membrane and penetrate the cells. In addition, scanning electron microscopy showed that MW10 caused significant morphological changes to the surface of the bacteria. Finally, an in vivo study utilizing a wound infection or healing model showed that LMWSC had the potential for use as a lead compound for the development of a novel anti-infective or healing compound.

Plasma Antioxidants Are Associated with Impaired Lung Function and COPD Exacerbations in Smokers

Low molecule weight antioxidants such as uric acid (UA), glutathione (GSH), and ascorbate (ASC) counter the effects of oxidants produced by cigarette smoke. Although dietary intake of foods rich in antioxidants has been associated with a reduced risk of smokers developing chronic obstructive pulmonary disease (COPD), the association between plasma antioxidants and COPD is less clear. In this cross-sectional study we investigated the relationship among plasma antioxidants and COPD phenotypes (severity of airflow obstruction on spirometry and history of exacerbations) in 136 smokers with normal lung function and 367 smokers with COPD. In the multivariate analysis, a lower plasma UA was associated with more severe COPD (P < 0.002) and a lower GSH was associated with a history of COPD exacerbations (P = 0.03); ASC was not associated with any COPD phenotypes. This suggests that antioxidant balance is impaired in smokers with obstruction on spirometry or a history of COPD exacerbations.

The use of multifunctional magnetic mesoporous core/shell heteronanostructures in a biomolecule separation system

A multifunctional magnetic mesoporous core/shell heteronanostructure (designated as Fe 3O 4@NiSiO 3) has been designed and constructed that combined the capacity of effective protein purification from protein mixture and selective low molecule weight (MW) biomolecule enrichment. The nanoparticle is composed by magnetite nanoparticle with immobilized metal ion surface and solid porous shell which presents a number of important features, such as controllable shell thickness, uniform pore size and excellent magnetism. By taking advantages of the high affinity of Ni 2+ on the shell surface toward His-tagged proteins and the fast response toward an assistant magnet, the heteronanoparticles can be applied to selectively bind to and magnetically separate of His-tagged proteins from a cell lysate of E. coli. Additionally, owing to the homogeneous 3D mesopores on the nickel silicate shell, the heteronanoparticles can selectively capture low MW biomolecules from complex mixture. Significantly, it is expected that this approach can be extended to other biomolecule separation and enrichment systems by changing the immobilized surface and the pore size.

Polymorphism of Amino Acid‐Based Dendrons: From Organogels to Microcrystals

There is a delicate balance for a low-weight molecule to behave as a gelator or crystal. The synthesis of two novel amino acid-based naphthalene-dendrons, Nap-G1 and Nap-G2 is described. Both dendrons display polymorphic properties in organic solvents. Nap-G1 developed a fibrous network with β-sheet architecture in cyclohexane but exhibited a spherulitic network in mixed solvents (chloroform/petroleum ether 1:5, v/v). On the other hand, Nap-G2 acted as an efficient organogelator in chloroform but formed crystalline fibers in relatively high polarity solvents (such as acetone and methanol). Combinations of characterizations have been employed to study the polymorphism.

Regulation of subtilisin‐like protease prC expression by nematode cuticle in the nematophagous fungus Clonostachys rosea

Nematophagous fungi have been used as biological control agents against nematodes parasitic to plants and animals. These fungi can secret subtilisin-like extracellular serine proteases during the infection of nematodes. The expression of these subtilisin-like serine proteases is regulated by nitrogen sources, including nematode cuticle. However, the mechanisms underlying the nitrogen sources-induced expression of these serine proteases is not well understood. In this study, we investigated the effect of nitrogen sources on the expression of a subtilisin-like extracellular protease, prC, in the nematophagous fungus Clonostachys rosea. Disruption of prC attenuated infection of the fungus to nematodes, indicating that this gene functions as a virulence factor. The inhibition of basal expression of prC by the preferred nitrogen sources (glutamine, ammonia) occurred at the transcriptional level. In contrast, nematode cuticle induced the expression of prC at the post-transcriptional level. The inducible expression of prC by nematode cuticle was significantly suppressed by glutamine, ammonia and phenylmethylsulfonyl fluoride (an inhibitor of serine protease). Thus, the existence of active PrC, albeit at a low level in the medium, is probably essential for further induction of this gene by nematode cuticle. Moreover, the low molecule weight (< 3 kD) degradation products of nematode cuticle could significantly induce the expression of prC. Ammonia suppresses the virulence of C. rosea against nematodes, probably by inhibiting prC expression. Thus, the nematophagous fungi probably could not function well as biocontrol agents in fields fertilized with a large amount of ammonium salt.