Plasma folate levels are associated with the lipoprotein profile: a retrospective database analysis

Background

Several studies demonstrated an association of homocysteine plasma levels and the plasma lipoprotein profile. This cross-sectional pilot study aimed at analyzing whether blood levels of the two important cofactors of homocysteine metabolism, folate and vitamin B12, coincide with the lipoprotein profile.

Methods

In a retrospective single center approach, we analyzed the laboratory database (2003-2006) of the University Hospital Bonn, Germany, including 1743 individuals, in whom vitamin B12, folate and at least one lipoprotein parameter had been determined by linear multilogistic regression.

Results

Higher folate serum levels were associated with lower serum levels of low density lipoprotein cholesterol (LDL-C; Beta = -0.164; p < 0.001), higher levels of high density lipoprotein cholesterol (HDL-C; Beta = 0.094; p = 0.021 for trend) and a lower LDL-C-C/HDL-C-ratio (Beta = -0.210; p < 0.001). Using ANOVA, we additionally compared the individuals of the highest with those of the lowest quartile of folate. Individuals of the highest folate quartile had higher levels of HDL-C (1.42 ± 0.44 mmol/l vs. 1.26 ± 0.47 mmol/l; p = 0.005), lower levels of LDL-C (3.21 ± 1.04 mmol/l vs. 3.67 ± 1.10 mmol/l; p = 0.001) and a lower LDL-C/HDL-C- ratio (2.47 ± 1.18 vs. 3.77 ± 5.29; p = 0.002). Vitamin B12 was not associated with the lipoprotein profile.

Conclusion

In our study sample, high folate levels were associated with a favorable lipoprotein profile. A reconfirmation of these results in a different study population with a well defined status of health, diet and medication is warranted.     

Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca²⁺ release from the sarcoplasmic reticulum (0 mM Ca²⁺), but it reduced the subsequent tonic phase characterised by Ca²⁺ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca²⁺ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K⁺ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.     

Towards the co-evolution of industrial products and its production systems by combining models from development and hardware/software deployment in cyber-physical systems

Industrial production systems and industrially manufactured products are constantly evolving due to technical innovations and customers’ demands. Therefore, ensuring an optimized co-evolution of both becomes an important yet challenging task. Approaches for model-based systems engineering have been widely investigated and have already had significant impact on industrial practice. However, existing model-based approaches mostly are focusing on particular aspects of a production system and do not provide a holistic approach for optimizing automated production systems, their deployment, and their co-evolution with the product. As a first step towards this direction, this contribution proposes the combination of an engineering approach for aPS based on systems modeling language with models and techniques for deployment of software and hardware to cyber-physical system architectures, which have been investigated in the field of computer science, and motivates the possibilities of a combined approach.     

Fabrication of diamond nanowires for quantum information processing applications

We present a design and a top-down fabrication method for realizing diamond nanowires in both bulk single crystal and polycrystalline diamond. Numerical modeling was used to study coupling between a Nitrogen Vacancy (NV) color center and optical modes of a nanowire, and to find an optimal range of nanowire diameters that allows for large collection efficiency of emitted photons. Inductively coupled plasma (ICP) reactive ion etching (RIE) with oxygen is used to fabricate the nanowires. Drop-casted nanoparticles (including Au, SiO₂ and Al₂O₃) as well as electron beam lithography defined spin-on glass and evaporated Au have been used as an etch mask. We found Al₂O₃ nanoparticles to be the most etch resistant. At the same time FOx e-beam resist (spin-on glass) proved to be a suitable etch mask for fabrication of ordered arrays of diamond nanowires. We were able to obtain nanowires with near-vertical sidewalls in both polycrystalline and single crystal diamond. The heights and diameters of the polycrystalline nanowires presented in this paper are ≈ 1 μm and 120–340 nm, respectively, having a 200 nm/min etch rate. In the case of single crystal diamond (types Ib and IIa) nanowires the height and diameter for different diamonds and masks shown in this paper were 1–2.4 μm and 120–490 nm with etch rates between 190 and 240 nm/min.     

Characterization of Oleogels Based on Waxes and Their Hydrolyzates

In this paper, the structuring of liquid oils, also known as oleogelation, is systematically investigated for the first time using a quasi-quaternary mixing system approach. Native waxes with different quantities of wax esters (WE), n-alkanes (hydrocarbons (HC)), fatty acids (FA), and fatty alcohols (FaOH) are applied in mixtures with hydrolyzed waxes to systematically change the composition. Hydrolyzed waxes contain high levels of FA and FaOH. The model systems are investigated on microscopic level (brightfield light microscopy (BFM), cryogenic scanning electron microscopy (cryo-SEM)) as well as on their macroscopic properties (rheology, gel hardness) and calorimetric behavior (differential scanning calorimetry (DSC)). It is found that sunflower wax (SFW)-based gels (12% structurant) become less hard on any admixture. Beeswax (BW)-based gels show significant increases in hardness when 25% and 50% (w/w) hydrolyzate are admixed. This could be related to stepwise crystallization. Further analysis reveals that the dissolution/melting behavior of the wax ester mixtures can be surprisingly well described as ideal solubility of a single pseudocomponent. The approach to unravel the individual contributions of the different species present in waxes is successful and marks a first step to better understand the systematic of wax functionality as oleogelators. Practical Application: The substitution of hardstock fats in structured oil phases is of interest for two reasons. The improved nutritional profile oleogels offer are beneficial for public health while the elimination of palm oil based ingredients appears to be a general public desire. Among the technical solutions for non-TAG oil structuring waxes are very promising. This is primarily due to their availability, prior consumption, potentially low cost for functionality. Currently waxes are technically and scientifically wrongly treated as single components. In order to better utilize the potential of waxes and design future sourcing strategies it is necessary to understand the wax functionality at a compositional/molecular level. This contribution marks the first step into this direction by considering classes of molecules with respect to their contribution to functionality. This understanding is considered as a key for future compositional design.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

Coaxial Alginate Hydrogels: From Self-Assembled 3D Cellular Constructs to Long-Term Storage

Alginate as a versatile naturally occurring biomaterial has found widespread use in the biomedical field due to its unique features such as biocompatibility and biodegradability. The ability of its semipermeable hydrogels to provide a favourable microenvironment for clinically relevant cells made alginate encapsulation a leading technology for immunoisolation, 3D culture, cryopreservation as well as cell and drug delivery. The aim of this work is the evaluation of structural properties and swelling behaviour of the core-shell capsules for the encapsulation of multipotent stromal cells (MSCs), their 3D culture and cryopreservation using slow freezing. The cells were encapsulated in core-shell capsules using coaxial electrospraying, cultured for 35 days and cryopreserved. Cell viability, metabolic activity and cell–cell interactions were analysed. Cryopreservation of MSCs-laden core-shell capsules was performed according to parameters pre-selected on cell-free capsules. The results suggest that core-shell capsules produced from the low viscosity high-G alginate are superior to high-M ones in terms of stability during in vitro culture, as well as to solid beads in terms of promoting formation of viable self-assembled cellular structures and maintenance of MSCs functionality on a long-term basis. The application of 0.3 M sucrose demonstrated a beneficial effect on the integrity of capsules and viability of formed 3D cell assemblies, as compared to 10% dimethyl sulfoxide (DMSO) alone. The proposed workflow from the preparation of core-shell capsules with self-assembled cellular structures to the cryopreservation appears to be a promising strategy for their off-the-shelf availability.     

Proteins Marking the Sequence of Genotoxic Signaling from Irradiated Mesenchymal Stromal Cells to CD34+ Cells

Non-targeted effects (NTE) of ionizing radiation may initiate myeloid neoplasms (MN). Here, protein mediators (I) in irradiated human mesenchymal stromal cells (MSC) as the NTE source, (II) in MSC conditioned supernatant and (III) in human bone marrow CD34+ cells undergoing genotoxic NTE were investigated. Healthy sublethal irradiated MSC showed significantly increased levels of reactive oxygen species. These cells responded by increasing intracellular abundance of proteins involved in proteasomal degradation, protein translation, cytoskeleton dynamics, nucleocytoplasmic shuttling, and those with antioxidant activity. Among the increased proteins were THY1 and GNA11/14, which are signaling proteins with hitherto unknown functions in the radiation response and NTE. In the corresponding MSC conditioned medium, the three chaperones GRP78, CALR, and PDIA3 were increased. Together with GPI, these were the only four altered proteins, which were associated with the observed genotoxic NTE. Healthy CD34+ cells cultured in MSC conditioned medium suffered from more than a six-fold increase in γH2AX focal staining, indicative for DNA double-strand breaks, as well as numerical and structural chromosomal aberrations within three days. At this stage, five proteins were altered, among them IQGAP1, HMGB1, and PA2G4, which are involved in malign development. In summary, our data provide novel insights into three sequential steps of genotoxic signaling from irradiated MSC to CD34+ cells, implicating that induced NTE might initiate the development of MN.     

Isolate-Specific Effect of Entomopathogenic Endophytic Fungi on Population Growth of Two-Spotted Spider Mite (Tetranychus urticae Koch) and Levels of Steroidal Glycoalkaloids in Tomato

Journal of Chemical Ecology - Entomopathogenic fungi (EPF) can be experimentally established in several plant species as endophytes. Ecological effects of EPF inoculations on plant growth and...