Multiple-Molecule Drug Design Based on Systems Biology Approaches and Deep Neural Network to Mitigate Human Skin Aging

Human skin aging is affected by various biological signaling pathways, microenvironment factors and epigenetic regulations. With the increasing demand for cosmetics and pharmaceuticals to prevent or reverse skin aging year by year, designing multiple-molecule drugs for mitigating skin aging is indispensable. In this study, we developed strategies for systems medicine design based on systems biology methods and deep neural networks. We constructed the candidate genomewide genetic and epigenetic network (GWGEN) via big database mining. After doing systems modeling and applying system identification, system order detection and principle network projection methods with real time-profile microarray data, we could obtain core signaling pathways and identify essential biomarkers based on the skin aging molecular progression mechanisms. Afterwards, we trained a deep neural network of drug–target interaction in advance and applied it to predict the potential candidate drugs based on our identified biomarkers. To narrow down the candidate drugs, we designed two filters considering drug regulation ability and drug sensitivity. With the proposed systems medicine design procedure, we not only shed the light on the skin aging molecular progression mechanisms but also suggested two multiple-molecule drugs for mitigating human skin aging from young adulthood to middle age and middle age to old age, respectively.     

Enhancement of the Antioxidant and Skin Permeation Properties of Betulin and Its Derivatives

This study investigated the antioxidant activity DPPH, ABTS, and Folin–Ciocalteu methods of betulin (compound 1) and its derivatives (compounds 2–11). Skin permeability and accumulation associated with compounds 1 and 8 were also examined. Identification of the obtained products (compound 2–11) and betulin isolated from plant material was based on the analysis of ¹H- NMR and ¹³C-NMR spectra. The partition coefficient was calculated to determine the lipophilicity of all compounds. In the next stage, the penetration through pig skin and its accumulation in the skin were evaluated of ethanol vehicles containing compound 8 (at a concentration of 0.226 mmol/dm³), which was characterized by the highest antioxidant activity. For comparison, penetration studies of betulin itself were also carried out. Poor solubility and the bioavailability of pure compounds are major constraints in combination therapy. However, we observed that the ethanol vehicle was an enhancer of skin permeation for both the initial betulin and compound 8. The betulin 8 derivative showed increased permeability through biological membranes compared to the parent betulin. The paper presents the transformation of polycyclic compounds to produce novel derivatives with marked antioxidant activities and as valuable intermediates for the pharmaceutical industry. Moreover, the compounds contained in the vehicles, due to their mechanism of action, can have a beneficial effect on the balance between oxidants and antioxidants in the body, minimizing the effects of oxidative stress. The results of this work may contribute to knowledge regarding vehicles with antioxidant potential. The use of vehicles for this type of research is therefore justified.     

pH‐Modulating Poly(ethylene glycol)/Alginate Hydrogel Dressings for the Treatment of Chronic Wounds

The development of chronic wounds has been frequently associated with alkaline pH values. The application of pH‐modulating wound dressings can, therefore, be a promising treatment option to promote normal wound healing. This study reports on the development and characterization of acidic hydrogel dressings based on interpenetrating poly(ethylene glycol) diacrylate/acrylic acid/alginate networks. The incorporation of ionizable carboxylic acid groups results in high liquid uptake up to 500%. The combination of two separate polymer networks significantly improves the tensile and compressive stability. In a 2D cell migration assay, the application of hydrogels (0% to 1.5% acrylic acid) results in complete “wound” closure; hydrogels with 0.25% acrylic acid significantly increase the cell migration velocity to 19.8 ± 1.9 µm h⁻¹. The most promising formulation (hydrogels with 0.25% acrylic acid) is tested on 3D human skin constructs, increasing keratinocyte ingrowth into the wound by 164%.

     

Use of Phosphoantimonic Acid for Arsenic Determination by Activation Analysi

A methed was elaborated to determine arsenic amount in skin samples by neutron activation analysis and high-resolution gamma spectrometry including sample preparation after mineralization by sorption on silicagel saturated with phosphoantimonic acid. The samples were irradiated in the VVR-S reactor core in a flux of 10¹³ neutrons · cm^?2 · s^?1, mineralized with a mixture of nitric and sulphuric acids, the gamma spectrum was measured after passing through an ion-exchanger containing 0.5 mol P₂O₅ to 1 mol Sb₂O₅ (SP-2) by a gamma-spectroscopy system PLURIMAT 20 with a Ge(Li) detector, and the ⁷⁶As photopeak of E_γ = 0.559 MeV was measured. The values of the results obtained varied in the range of (4?5 )× 10^?1 ppm arsenic. The sensitivity of the proposed determination method is l×10^?3 μg arsenic.     

钴基非晶丝的巨磁阻抗效应实验装置设计

介绍了巨磁阻抗效应的原理,提出了测量方法,分析巨磁阻抗效应随频率、外加磁场的变化规律.研究表明在6~21 MHz范围内,100 mT磁场下巨磁阻抗可达-50%以上,并且在30~40 mT磁场下巨磁阻抗即可达到-40%.     

Antioxidant activity of grape skin aqueous extracts from pressurized hot water extraction combined with electron paramagnetic resonance spectroscopy

Pressurized hot water extraction (PHWE) was employed to prepare extracts from dried grape skin of two wine grape varieties (St. Laurent and Alibernet) at various temperatures (from 40 up to 120 °C) and amounts of sample (0.5, 1.0 and 1.5 g). To assess the antioxidant activity of the extracts, electron paramagnetic resonance (EPR) spectroscopy was applied involving DPPH and ABTS⁺ assays. Other extract characteristics including HPLC profile of anthocyanins and total phenolic compound content were obtained as well. PHWE has also been compared with earlier results of extractions of the same grape skin samples with compressed methanol and compressed ethanol under the conditions of pressurized fluid extraction (PFE). From this comparison, PHWE emerges as the more benign and efficient extraction method to recover valuable phenolic antioxidants from grape skins for the prospective use in functional food supplements.     

On the Stagnation Point Flow of a Special Class of Non-Newtonian Fluids

Abstract

The two-dimensional boundary layer equations for a class of non-Newtonian fluids, for which the apparent viscosity can be expressed as a polynomial in the second scalar invariant of the rate of strain tensor, have been derived. These equations have been employed to analyse the flow near a stagnation point over a stationary impermeable wall. The non-Newtonian effects on the boundary layer velocity profile and the wall skin friction have been studied, and compared with the corresponding Newtonian fluid. The fluid velocity in the boundary layer has been shown to be retarded by the non-Newtonian effect while the skin friction increases proportionate to it.     

An Extraction Method for Obtaining the Maximum Non-Anthocyanin Phenolics from Grape Berry Skins

To obtain maximum non-anthocyanin phenolics from grape skins, various extraction conditions were evaluated according to the amounts of 8 non-anthocyanin phenolics. The result showed that the optimal extraction was performed in ethyl acetate solution at 25°C, with liquid/solid ratio of 10:1 (ml/g) and for 30 min. On this basis, the non-anthocyanin extracts from two red and two white grape cultivars were analyzed using high performance liquid chromatography coupled with tandem mass spectrometry (HPLC- MS/MS), and twenty-four compounds were qualified and simultaneously quantified, which indicated that the present extraction method was suitable for the study of non-anthocyanin in grape skins.     

Design and Fabrication of Artificial Skin: Chitosan and Gelatin Immobilization on Silicone by Poly Acrylic Acid Graft Using a Plasma Surface Modification Method

Acrylic acid (AAc) was grafted onto the surfaces of polydimethylsiloxane (PDMS) films using a two-step oxygen plasma treatment. The first step of this method included oxygen plasma pretreatment of the PDMS films, immersion in AAc, and drying. The second step was carried out by plasma polymerization of the preadsorbed reactive AAc on the surfaces of the dried pretreated films. Then chitosan and gelatin were immobilized onto the poly(acrylic acid) grafted silicone through covalent bonding. The films were characterized by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and water contact angle measurements. Fibroblast cells (L929) were cultured onto the chitosan- and gelatin-immobilized poly(acrylic acid)-grafted silicone and poly(acrylic acid)-grafted silicone films. It was observed that the chitosan- and gelatin-immobilized surfaces showed significant cell growth in comparison with poly(acrylic acid)-grafted silicone samples. It seems that chitosan- and gelatin-immobilized surfaces may have an excellent potential to be used as a derm-like matrix.