Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.     

微纳层叠聚丙烯腈凝胶流动特性的数值模拟研究

建立了层叠流道的三维模型和有限元网格模型，根据流变测试数据，采用Polymat对物料的黏度模型参数进行拟合，并利用Polyflow软件对聚丙烯腈（PAN）凝胶在层叠流道内的三维等温流动过程进行了数值模拟分析。研究发现，当入口流量增大时，层叠流道出口速度的不均匀性增加；沿流动方向流道内压力逐渐降低，并在出口处降低至同一最低值；流道进出口压力差与入口流量大小具有正相关性；在流道的中心截面上剪切速率分布均匀，波动较小。     

虚实结合的可穿戴产品适合性检验研究

目的 为了更科学地研究和检验可穿戴产品的适合性,提出一种适合性检验方法,能够精确保留现实环境中的产品佩戴关系,并能将现实与虚拟的适合性检验研究相结合,得到合理的适合性检验结果.方法 以虚拟现实眼镜的适合性检验为例,通过高精度的三维测量技术将现实环境中的人、产品以及人—产品佩戴关系转化为三维虚拟信息,并以人—产品佩戴三维模型为参考基准对齐人和产品的虚拟模型,得到保留现实佩戴关系的人—产品佩戴模型组,再应用偏差分析法得出人—机佩戴区域的可视化适合性结果和统计数据,结合主观评价方法进一步分析产品的适合性.结论 虚实结合的产品适合性检验方法可在虚拟环境中高精度地保留现实环境中的人—产品佩戴关系,并能得到可视化的适合性检验结果,为检验和指导产品的适合性提供依据.     

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.     

Metabolic Profiling of VOCs Emitted by Bacteria Isolated from Pressure Ulcers and Treated with Different Concentrations of Bio-AgNPs

Considering the advent of antibiotic resistance, the study of bacterial metabolic behavior stimulated by novel antimicrobial agents becomes a relevant tool to elucidate involved adaptive pathways. Profiling of volatile metabolites was performed to monitor alterations of bacterial metabolism induced by biosynthesized silver nanoparticles (bio-AgNPs). Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis were isolated from pressure ulcers, and their cultures were prepared in the presence/absence of bio-AgNPs at 12.5, 25 and 50 µg mL⁻¹. Headspace solid phase microextraction associated to gas chromatography–mass spectrometry was the employed analytical platform. At the lower concentration level, the agent promoted positive modulation of products of fermentation routes and bioactive volatiles, indicating an attempt of bacteria to adapt to an ongoing suppression of cellular respiration. Augmented response of aldehydes and other possible products of lipid oxidative cleavage was noticed for increasing levels of bio-AgNPs. The greatest concentration of agent caused a reduction of 44 to 80% in the variety of compounds found in the control samples. Pathway analysis indicated overall inhibition of amino acids and fatty acids routes. The present assessment may provide a deeper understanding of molecular mechanisms of bio-AgNPs and how the metabolic response of bacteria is untangled.     

Microstructure and electromagnetic properties of LiFe5O8 ferrite ceramics prepared from wet- and dry-milled powders

The effect of dry and wet ball milling of LiFe₅O₈ ferrite powder on the microstructure and electromagnetic properties of ferrite ceramics was studied using XRD analysis, scanning electron microscopy, dilatometry, thermogravimetry, calorimetry, and measurement of specific magnetization and electrical resistance. The sintering temperature was 1050 °C; the sintering time was 2 h. It was found that ferrite fabricated from dry-milled powder exhibits an ordered α-LiFe₅O₈ phase with bulk density of 91%. Its saturation magnetization and Curie temperature are 55 emu/g and 628°С, respectively. Specific electrical resistance is 4?10⁶ Ω cm. Wet milling in isopropyl alcohol causes formation of a disordered β-LiFe₅O₈ phase. Ceramics produced by this method shows higher bulk density (97%) and low porosity, and an order of magnitude lower resistivity. Its saturation magnetization and Curie temperature are 51 emu/g and 607°С, respectively.     

High dielectric constant of NiFe2O4–LaFeO3 nanocomposite: Interfacial conduction and dielectric loss

Materials exhibiting colossal dielectric constant are the most sought-after materials due to their variety of applications in various electronics industries. NiFe₂O₄ and LaFeO₃ belonging to the spinel and perovskite structures, respectively, were coupled into a nanocomposite by adapting a one-pot sol-gel synthesis. The ratio of NiFe₂O₄:LaFeO₃ was varied and the synthesized materials were studied for their dielectric behaviors. Interestingly, among the samples studied, the nanocomposite with the ratio of 1:2 of NiFe₂O₄–LaFeO₃ exhibited a high dielectric constant value of 10390 at a frequency of 1 kHz with a several-fold increase in conductivity. The high conductivity resulted in a high dielectric loss. The origin of such a high dielectric constant and loss have been attributed to the Maxwell-Wagner type space charge polarization arising from the microstructure that consists of large and continuous grain boundaries, and the conducting phase at the interface, respectively.