Ligand–Histone H1 Conjugates: Increased Solubility of DNA Complexes, But No Enhanced Transfection Activity

We introduced galactose and a short RGD sequence as ligands into H1 histone to target the asialoglycoprotein receptor or integrins on cells expressing these receptors. The efficiency of the gene transfer mediated by galactosylated H1 histone was strongly affected by the transfection conditions. Galactosylation of H1 led to an increase of the basic H1-mediated gene transfer activity only, when H1 itself did not develop its optimal transfection activity. Under other conditions any specific gene transfer mediated by the asialoglycoprotein receptor was covered by the high transfection efficiency of H1 itself. Similar results of a marginal increase in the transfection efficiency were obtained by conjugates of a short RGD sequence and H1. This unexpected failure in the receptor specificity of both conjugates could be due to the unspecific cell-binding capacity of the H1 moiety and to increasing solubility of the complexes as shown by gel shift and solubility measurements.     

Study on Different Modification Methods of Collagen for Tissue Engineering

Because of the excellent biocompatibility and its specific amino sequences, collagen is an ideal biomedical material for tissue engineering applications. But collagen is usually lack of mechanical strength to form a rigid 3-D matrix and lack of ability to resist collagenase. In order to be a tissue engineering scaffold, collagen must strengthen its structures by modifying with chemical crosslinkers. Chemical crosslinkers used for modif- ying collagen fibers include glutaraldehyde （GA）, epoxy compounds （PC） and carbodiim- ides （EDC）. The aim of this study is to choose the best chemical crosslinker from the three reagents. In terms of the resistance to collagenase degradation, chemical cross-link- ing with PC provided the best protection; in terms of the mechanical characterization, chemical cross-linking with GA provided the best;and in terms of the biocompatibility, chemical cross-linking with EDC provided the best. There is not a reagent which has all merits for collagen crosslinking, so we should select the crosslinking reagent as the demands of use ask.     

Photoinitiating Ability of Pyrene–Chalcone-Based Oxime Esters with Different Substituents

With the rapid development of new irradiation setups as well as the ongoing interest in 3D printing, photopolymerization is extensively studied during the last decades. In photopolymerization, a photoinitiator and/or photosensitizer play(s) a crucial role in the photoinitiation step as this component absorbs light, thus creating the initiating species. In this study, a series of 17 chalcone-based oxime esters (OXEs) featuring the pyrene chromophore are designed, synthesized, and studied for their photoinitiation properties upon irradiation with visible light. Precisely, their photoinitiation abilities are examined during the free radical photopolymerization of acrylates under the irradiation of light-emitting diode (LED) at 405 nm. In the series of oxime esters, five of them demonstrate excellent photoinitiation abilities. Their thermal initiation abilities are also examined. To improve their photoinitiation abilities, these type I photoinitiators are also tested as type II photoinitiators in two-component photoinitiating systems using bis-(4-tert-butylphenyl)iodonium or ethyl 4-(dimethylamino)benzoate as additives. In this process, the OXE-B/iodonium system shows the best photopolymerization. To develop the use of these chalcone-based oxime esters, the best OXE is used as a monocomponent photoinitiating system in 2D laser writing at 405 nm. The design of composites using glass fibers or carbon fiber as fillers is also examined.     

Reactivity of the EEG μ Rhythm on Observing and Performing Actions in Young Children with Different Levels of Receptive Speech Development

Neuroscience and Behavioral Physiology - The reactivity of EEG power in the individually defined μ frequency ranges was studied in the central, frontal, and parietal EEG leads in children...     

The Role of β1,2-Adrenoceptors in the Amygdala in the Behavior of Rats with Different Levels of Freezing in Conditioned Reflex Fear

Neuroscience and Behavioral Physiology - Individual sensitivity to blockade of β1,2-adrenoceptors was studied by dividing rats into groups depending on the manifestation of conditioned reflex...     

Modification of Polyurethane with Polyethylene Glycol–Corn Trypsin Inhibitor for Inhibition of Factor Xlla in Blood Contact

Abstract

In previous work using gold as a model substrate, we showed that modification of surfaces with poly(ethylene glycol) (PEG) and corn trypsin inhibitor (CTI) rendered them protein resistant and inhibitory against activated factor XII. Sequential attachment of PEG followed by CTI gave superior performance compared to direct attachment of a preformed PEG-CTI conjugate. In the present work, a sequential method was used to attach PEG and CTI to a polyurethane (PU) substrate to develop a material with applicability for blood-contacting medical devices. Controls included surfaces modified only with PEG and only with CTI. Surfaces were characterized by water contact angle and X-ray photoelectron spectroscopy. The surface density of CTI was in the range of a monolayer and was higher on the PU substrate than on gold reported previously. Biointeractions were investigated by measuring fibrinogen adsorption from buffer and plasma, factor XIIa inhibition and plasma clotting time. Both the PU–PEG surfaces and the PU–PEG–CTI surfaces showed low fibrinogen adsorption from buffer and plasma, indicating that PEG retained its protein resistance when conjugated to CTI. Although the CTI density was lower on PU–PEG–CTI than on PU modified only with CTI, PU–PEG–CTI exhibited greater factor XIIa inhibition and a longer plasma clotting time, suggesting that PEG facilitates the interaction of CTI with factor XIIa. Thus sequential attachment of PEG and CTI may be a useful approach to improve the thromboresistance of PU surfaces.     

Management of Relapsed or Refractory Hodgkin Lymphoma with Second-Generation Antibody–Drug Conjugates: Focus on Brentuximab Vedotin

Brentuximab vedotin (Adcetris, Seattle Genetics) is an antibody–drug conjugate (ADC) that joins an anti-CD 30 monoclonal antibody with the anti-tubulin agent monomethyl auristatin E via a dipeptide linker. It has demonstrated significant activity in CD 30-positive lymphomas and is currently approved by the US FDA for treatment of Hodgkin lymphoma that has relapsed following autologous stem-cell transplantation, or after two lines of chemotherapy in non-transplant candidates. Brentuximab vedotin has also been approved for the treatment of relapsed anaplastic large-cell lymphoma after front-line chemotherapy. We briefly review the biology of Hodgkin lymphoma, with a focus on the pathogenic role of CD 30 as well as the development of CD 30-targeted therapy. We also discuss both the current role of brentuximab vedotin in the management of relapsed and refractory Hodgkin lymphoma and the likely future developments for this agent.     

Localization of Sources Generating the EEG α Rhythm during Observation,Performance, and Imitation of Operant Movements in Subjects with Different Intelligence Levels

Neuroscience and Behavioral Physiology - Use of the sLORETA method in 62 adult subjects with different intelligence levels located sources generating rhythms in the frequency band 8–12 Hz...     

The characteristics and transfection efficiency of cationic poly (ester–co–urethane) – short chain PEI conjugates self-assembled with DNA

To improve the transfection efficiency of polycations with DNA, we synthesized poly(ester–co–urethane)(PEU-g-PEI800) with short chain PEI800 in the side chain, and poly(ester–co–urethane)(PEU) without short chain PEI800. Both PEU-g-PEI800 and PEU, readily self-assembled with plasmid DNA (pCMV-βgal) in a HEPES buffer, were characterized by dynamic light scattering and zeta-potential. The results reveal that PEU-g-PEI800 and PEU were able to self-assemble particles with DNA and yield nano-sized complexes (<200 nm) with positive charge at N/P ratios of 20/1 and 120/1, respectively. The degradation studies indicate that the half-life of PEU-g-PEI800 and PEU in the HEPES buffer were 14 and 35 h at pH 7.4, respectively. Titration studies were performed to determine the buffering capacities of the polymers. The COS-7 cell viabilities in the presence of PEU-g-PEI800/DNA, PEU/DNA, and PEI25k/DNA were studied. In addition, The PEU-g-PEI800/DNA complexes were able to transfect COS-7 cells in vitro with a high efficiency comparable to a well-known gene carrier PEI25k. The results indicate that PEU-g-PEI800 is an attractive cationic poly (ester–co–urethane) for gene delivery and an interesting candidate for further study.     

Practical Considerations for the Pharmacokinetic and Immunogenic Assessment of Antibody–Drug Conjugates

Currently, the most bioanalytically challenging drugs are antibody–drug conjugates (ADCs), constructs comprising a monoclonal antibody and a cytotoxic drug connected by a linker. The bioanalytical challenges arise from the heterogeneous nature of ADCs and their complex in vivo behavior, resulting in a high number of analytes to be measured. Measuring the concentration of biologics in blood/plasma/serum is a necessity to properly assess their pharmacokinetic (PK)/pharmacodynamic behaviors in vivo. An additional bioanalytical challenge is to monitor the stability of the ADCs, as cytotoxic drugs released from the ADC in blood circulation may pose a potential safety risk because of their high cytotoxic potency. The nature of ADCs does not only complicate bioanalysis, but also immunogenicity assessment. Questions, such as ‘Which part of the ADCs is the anti-drug antibodies directed against?’ may arise, and their answer normally includes several immunogenicity risk assessment strategies. This review will focus on the bioanalytical challenges of ADCs, current approaches involving ligand-binding assays (LBAs), liquid chromatography and mass spectrometry platforms, and recommendations on which approach to use for which stage of drug development, and will close with immunogenicity assessment. In order to appropriately tackle the bioanalytical and immunogenic challenges of ADCs and consider every angle, the authors of this review have expertise in ligand binding and liquid chromatography–mass spectrometry.     

Many Ways–One Destination: Different Types of Neutrophils Death

Neutrophils constitute the most numerous populations of peripheral blood leukocytes, fulfilling the fundamental role in the development of the innate immune response. As the cells of the first line of defense, they guard the organism against the spread of pathogenic microorganisms. Neutrophils, similar to the other cells of the immune system, enter the path of death after fulfilling their biological function. Depending on the conditions that they are found in, they may undergo different types of cell death which requires the involvement of numerous signaling pathways. In this review article, we summarize the current state of knowledge regarding the different forms of neutrophil death, such as apoptosis, necrosis, necroptosis, autophagy, NETosis and pyroptosis.     

Elevated Levels of Circulating Immunostimulatory 90K in Henoch–Schoenlein Purpura

In order to clarify the immunologic reaction present in Henoch–Schoenlein purpura (HSP), 20 children (11 boys and 9 girls; median age, 5.8 ± 2.8 years) with HSP and 20 sex- and age-matched healthy children were studied. The 90K/Mac-2 BP serum concentrations were significantly higher in the patients than in the healthy controls (12.5 ± 7.5 vs 4.5 ± 2.7 g/ml, respectively; P < 0.0001). 90K/Mac-2 BP values higher than the cutoff value were observed in 13 of 20 (65%) patient. The soluble intercellular adhesion molecule 1 concentrations were significantly higher in HSP patients than controls (P < 0.0001), with mean values of 1631 ± 703 and 85 ± 16 ng/ml, respectively. The 90K/Mac-2 BP serum levels were significantly correlated with soluble intercellular adhesion molecule 1 ( r = 0.90, P < 0.0001). Although the underlying causes of these immunological abnormalities are unclear, these observations suggest that the 90K/Mac-2 BP protein may play a role in the immunological reactions involved in the development of HSP.     

Different expressions of latent HCMV genes in UL133–UL138 locus was associated with systemic lupus erythematosus

Human cytomegalovirus (HCMV), a member of the β-herpesvirus subfamily, establishes a life-long latent infection in the majority of the worldwide human. Accumulating studies have suggested that HCMV infection was a vital risk for SLE development. However, till to now, few studies carefully evaluated the relationship between HCMV latent infection and SLE. In this study, PBMCs from 92 SLE patients, and 81 controls were collected. The expression of viral genes in the UL133–UL138 locus in the isolated PBMCs was detected by our previous two-step nested RT-PCR. The relationship between the expression of viral genes in PBMCs and clinical indicators of SLE patients were further analyzed. Data indicated that the expression prevalence of UL133–UL138 was significant higher in the SLE patients, whereas UL135 and UL136 were detected only in the PBMC of the SLE populations. Correlation analysis of the expression of HCMV UL133–UL138 in the PBMCs and clinical indicators of the SLE patients suggested that UL133, UL135, UL136 were associated with various clinical parameters of the SLE patients. Especially, the SLE individuals with positive UL135 and/or UL136 genes had pancytopenia symptoms, including lymphocytopenia, monocytopenia and oligocythemia. In conclusion, our data confirm that the HCMV latent infection might also play a vital role in both the occurrence and development of SLE.     

Primary Research of MSCs on AW Glass Ceramic with Different Surface Roughness

1 IntroductionTissue engineering can be defined as the use of composite of cells and materials to promote a replace new tissue formation. The surface topography of the composite including surface texture and surface roughness, can directly influence cellular adsorb, attachment, proliferation differentiation and migradtion. Roughened surfaces were achieved through processes such as machining, particle blasting, chemical/electrochemical etching.Apatite-wallastonite glass-ceramic(AW GC) was dev…     

Synthesis and characterisation of a new superelastic Ti–25Ta–25Nb biomedical alloy

In this study, a new Ti–25Ta–25Nb (mass%) beta alloy was synthesised by cold crucible semi-levitation melting. This technique made it possible to obtain homogeneous ingots although the elements used have very different melting points. After melting, a thermo-mechanical treatment was applied in order to obtain a perfectly recrystallised beta microstructure. For this alloy composition, the tensile tests showed a very low Young’s modulus associated with an important super-elastic behaviour, which contributes to decrease the elastic modulus under stress and to increase the recoverable strain. On the other hand, the corrosion tests, which were carried out in a neutral Ringer solution, indicated a corrosion resistance higher than that of the commercially pure CP Ti alloy. These results show that this new alloy possesses all the characteristics necessary for its long-term use in medical implants.