Transdermal Delivery Systems for Ibuprofen and Ibuprofen Modified with Amino Acids Alkyl Esters Based on Bacterial Cellulose

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.     

Iron-aluminium pair reconfiguration processes in SiGe alloys

For the iron-aluminium pair in silicon it is possible to observe a deeper and stable first-nearest neighbour configuration and a shallower metastable more distant pair. Depending on sample cooling conditions it is possible to convert some of the stable pairs to metastable ones in a fully reversible process. The conversion process is a single jump of the iron between two neighbouring interstitial sites. In this study we have analysed how the electronic levels of the pair in both configurations are modified in SiGe by the alloying effects. We have also investigated to what extent the presence of germanium atoms in the crystal matrix affects the dynamics of the single iron jump process. These studies have been performed using Czochralski-grown unstrained aluminium-doped Si_1−x Ge _x crystals (0 < x < 0.056). Local environments of the Fe_iAl_s pairs have been observed as structures seen in high-resolution Laplace DLTS spectra. It has been observed that the energy separation of the main and subsidiary peaks are similar for both pair configurations which indicates that for iron the alloy effect is similar for both its interstitial positions.     

Analysis of AAC walls subjected to vertical load

The paper describes the results of testing six autoclaved aerated concrete (AAC) walls on a natural scale. The walls were made of 18 cm wide blocks and thin layer joints. Reinforced and non‐reinforced walls were tested. Basalt grids and typical steel reinforcement (truss type) were used as reinforcements. The load was applied by a reinforced concrete rim beam. In the first part of the tests, the impact of the opening (window) on stress distribution and the load capacity of the wall was analysed. In the second part of the tests, the unequally loaded connection zone of perpendicular walls was analysed. The results were used to draw practical conclusions on rules of additional reinforcement of zones surrounding openings and connection zones of perpendicular walls.     

Simulations and analyses of arched brick structures

The paper presents problems related to the assessment of historical objects, especially brick arch structures, in view of potential improvement of their strength using various technologies. We have presented the methodology and computer simulations used for assessment of present strain and load bearing capacity of brick arches along with a variety of reinforcement techniques. We also present arch deformation FEM analysis along with results of assessment of actual objects.     

Structural Integrity of the A147T Polymorph of Mammalian TSPO

Ligands of the transmembrane protein TSPO are used for imaging of brain inflammation, but a common polymorphism in TSPO complicates their application to humans. Here we determined the three‐dimensional structure and side‐chain dynamics of the A147T polymorph of mammalian TSPO in complex with the first‐generation ligand PK11195. We show that A147T TSPO is able to retain the same structural and dynamic profile as the wild‐type protein and thus binds PK11195 with comparable affinity. Our study is important for the design of more potent diagnostic and therapeutic ligands of TSPO.     

The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis

Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.     

Asymmetric Synthesis of 3,4‐Dihydrocoumarins Bearing an α,α‐Disubstituted Amino Acid Moiety

An organocatalytic approach for the stereoselective synthesis of 3,4‐dihydrocoumarins with an α,α‐disubstituted amino acid moiety incorporated is presented. The developed methodology is based on the cascade reaction between α‐substituted azlactones and 2‐hydroxychalcones. It is initiated by a chiral Brønsted base‐catalyzed enantio‐ and diastereoselective Michael reaction followed by the azlactone ring opening to construct a 3,4‐dihydrocoumarin framework. Products bearing two adjacent stereogenic centers, one being quaternary, were formed with high enantioselectivities and excellent diastereoselectivities. Furthermore, the complete regioselectivity of the new cascade reactivity is worthy of notice.

     

Modulation of CD14 and TLR4⋅MD‐2 Activities by a Synthetic Lipid A Mimetic

Monosaccharide lipid A mimetics based on a glucosamine core linked to two fatty acid chains and bearing one or two phosphate groups have been synthesized. Compounds 1 and 2 , each with one phosphate group, were practically inactive in inhibiting LPS‐induced TLR4 signaling and cytokine production in HEK‐blue cells and murine macrophages, but compound 3 , with two phosphate groups, was found to be active in efficiently inhibiting TLR4 signal in both cell types. The direct interaction between compound 3 and the MD‐2 coreceptor was investigated by NMR spectroscopy and molecular modeling/docking analysis. This compound also interacts directly with the CD14 receptor, stimulating its internalization by endocytosis. Experiments on macrophages show that the effect on CD14 reinforces the activity on MD‐2 ? TLR4 because compound 3 's activity is higher when CD14 is important for TLR4 signaling (i.e., at low LPS concentration). The dual targeting of MD‐2 and CD14, accompanied by good solubility in water and lack of toxicity, suggests the use of monosaccharide 3 as a lead compound for the development of drugs directed against TLR4related syndromes.     

DArTseq-Based High-Throughput SilicoDArT and SNP Markers Applied for Association Mapping of Genes Related to Maize Morphology

Today, agricultural productivity is essential to meet the needs of a growing population, and is also a key tool in coping with climate change. Innovative plant breeding technologies such as molecular markers, phenotyping, genotyping, the CRISPR/Cas method and next-generation sequencing can help agriculture meet the challenges of the 21st century more effectively. Therefore, the aim of the research was to identify single-nucleotide polymorphisms (SNPs) and SilicoDArT markers related to select morphological features determining the yield in maize. The plant material consisted of ninety-four inbred lines of maize of various origins. These lines were phenotyped under field conditions. A total of 14 morphological features was analyzed. The DArTseq method was chosen for genotyping because this technique reduces the complexity of the genome by restriction enzyme digestion. Subsequently, short fragment sequencing was used. The choice of a combination of restrictases allowed the isolation of highly informative low copy fragments of the genome. Thanks to this method, 90% of the obtained DArTseq markers are complementary to the unique sequences of the genome. All the observed features were normally distributed. Analysis of variance indicated that the main effect of lines was statistically significant (p < 0.001) for all 14 traits of study. Thanks to the DArTseq analysis with the use of next-generation sequencing (NGS) in the studied plant material, it was possible to identify 49,911 polymorphisms, of which 33,452 are SilicoDArT markers and the remaining 16,459 are SNP markers. Among those mentioned, two markers associated with four analyzed traits deserved special attention: SNP (4578734) and SilicoDArT (4778900). SNP marker 4578734 was associated with the following features: anthocyanin coloration of cob glumes, number of days from sowing to anthesis, number of days from sowing to silk emergence and anthocyanin coloration of internodes. SilicoDArT marker 4778900 was associated with the following features: number of days from sowing to anthesis, number of days from sowing to silk emergence, tassel: angle between the axis and lateral branches and plant height. Sequences with a length of 71 bp were used for physical mapping. The BLAST and EnsemblPlants databases were searched against the maize genome to identify the positions of both markers. Marker 4578734 was localized on chromosome 7, the closest gene was Zm00001d022467, approximately 55 Kb apart, encoding anthocyanidin 3-O-glucosyltransferase. Marker 4778900 was located on chromosome 7, at a distance of 45 Kb from the gene Zm00001d045261 encoding starch synthase I. The latter observation indicated that these flanking SilicoDArT and SNP markers were not in a state of linkage disequilibrium.