Unveiling new genetic insights in rheumatoid arthritis for drug discovery through Taxonomy3 analysis.

Genetic support for a drug target has been shown to increase the probability of success in drug development, with the potential to reduce attrition in the pharmaceutical industry alongside discovering novel therapeutic targets. It is therefore important to maximise the detection of genetic associations that affect disease susceptibility. Conventional statistical methods such as genome-wide association studies (GWAS) only identify some of the genetic contribution to disease, so novel analytical approaches are required to extract additional insights. C4X Discovery has developed Taxonomy3, a unique method for analysing genetic datasets based on mathematics that is novel in drug discovery. When applied to a previously published rheumatoid arthritis GWAS dataset, Taxonomy3 identified many additional novel genetic signals associated with this autoimmune disease. Follow-up studies using tool compounds support the utility of the method in identifying novel biology and tractable drug targets with genetic support for further investigation.

Whey Protein Isolate as a Substrate to Design Calendula officinalis Flower Extract Controlled-Release Materials.

The use of natural active substances and the development of new formulations are promising directions in the cosmetic and pharmacy industries. The primary purpose of this research was the production of microparticles based on whey protein isolate (WPI) and calcium alginate (ALG) containing Calendula officinalis flower extract and their incorporation into films composed of gelatin, WPI, and glycerol. Both swollen and dry microparticles were studied by optical microscopy and their sizes were measured. Water absorption by the microparticles, their loading capacity, and the release profile of flower extract were also characterized. The films were analyzed by mechanical tests (Young's modulus, tensile strength, elongation at break), swelling capacity, contact angle, and moisture content measurements. The presented data showed that the active ingredient was successfully enclosed in spherical microparticles and completely released after 75 min of incubation at 37 °C. The incorporation of the microparticles into polymer films caused a decrease in stiffness and tensile strength, simultaneously increasing the ductility of the samples. Moreover, the films containing microparticles displayed higher swelling ability and moisture content compared to those without them. Hence, the materials prepared in this study with Calendula officinalis flower extract encapsulated into polymeric microspheres can be a starting point for the development of new products intended for skin application; advantages include protection of the extract against external factors and a controlled release profile.

Gelatin and gelatin/starch-based films modified with sorbitol for wound healing.

Gelatin-based films modified with sorbitol were produced from gelatin solution or gelatin/starch blends using a simple and low-cost solvent casting method, and subsequently, their physicochemical, mechanical, and biocompatibility properties were characterized. This work focused on developing and optimizing a biopolymeric blend to improve the pure biopolymers' properties for potential biomedical applications such as wound dressing. The films were characterized in terms of morphology and transparency, mechanical, moisture and swelling properties, thermal stability, and degradation potential. Moreover, hemocompatibility, as well as cytocompatibility of prepared films, were examined. The addition of sorbitol contributed to improving mechanical properties, swelling reduction, and increasing biostability over time. The cytocompatibility of obtained films was confirmed in vitro with two different human cell lines, fibroblastic and osteoblastic, and a more favorable cellular response was received for fibroblasts. Further, in hemocompatibility studies, it was found that all films may be classified as non-hemolytic as they did not have a negative effect on the human erythrocytes. The obtained results indicate the great potential of the gelatin/starch blends modified with sorbitol as regenerative biomaterials intended for wound healing applications.

Stability Studies, Biodegradation Tests, and Mechanical Properties of Sodium Alginate and Gellan Gum Beads Containing Surfactant.

The excessive presence of single-use plastics is rapidly degrading our natural environment on a global scale due to their inherent resistance to decomposition. Wet wipes used for personal or household purposes contribute significantly to the accumulation of plastic waste. One potential solution to address this problem involves developing eco-friendly materials that possess the ability to degrade naturally while retaining their washing capabilities. For this purpose, the beads from sodium alginate, gellan gum, and a mixture of these natural polymers containing surfactant were produced using the ionotropic gelation method. Stability studies of the beads by observing their appearance and diameter were performed after incubation in solutions of different pH values. The images showed that macroparticles were reduced in size in an acidic medium and swelled in solution of pH-neutral phosphate-buffered saline. Moreover, all the beads first swelled and then degraded in alkaline conditions. The beads based on gellan gum and combining both polymers were the least sensitive to pH changes. The compression tests revealed that the stiffness of all macroparticles decreased with the increasing pH of the solutions in which they were immersed. The studied beads were more rigid in an acidic solution than in alkaline conditions. The biodegradation of macroparticles was assessed using a respirometric method in soil and seawater. It is important to note that the macroparticles degraded more rapidly in soil than in seawater.

A Look at the Spatial Confining Effect on the Molecular Electrostatic Potential (MEP)-A Case Study of the HF and BrCN Molecules.

In this theoretical study, we report on the molecular electrostatic potential (MEP) of titled molecules confined by repulsive potentials of cylindrical symmetry mimicking a topology. Our calculations show that the spatial restriction significantly changes the picture of the MEP of molecules in a quantitative and qualitative sense. In particular, the drastic changes in the MEP as a function of the strength of spatial confinement are observed for the BrCN molecule. This preliminary study is the first step in the investigation of the behavior of the MEP of molecular systems under orbital compression.

From Supramolecular Hydrogels to Multifunctional Carriers for Biologically Active Substances.

Supramolecular hydrogels are 3D, elastic, water-swelled materials that are held together by reversible, non-covalent interactions, such as hydrogen bonds, hydrophobic, ionic, host-guest interactions, and metal-ligand coordination. These interactions determine the hydrogels' unique properties: mechanical strength; stretchability; injectability; ability to self-heal; shear-thinning; and sensitivity to stimuli, e.g., pH, temperature, the presence of ions, and other chemical substances. For this reason, supramolecular hydrogels have attracted considerable attention as carriers for active substance delivery systems. In this paper, we focused on the various types of non-covalent interactions. The hydrogen bonds, hydrophobic, ionic, coordination, and host-guest interactions between hydrogel components have been described. We also provided an overview of the recent studies on supramolecular hydrogel applications, such as cancer therapy, anti-inflammatory gels, antimicrobial activity, controlled gene drug delivery, and tissue engineering.

Freeze-Dried Matrices Composed of Degradable Polymers with Surfactant-Loaded Microparticles Based on Pectin and Sodium Alginate.

Gelatin/polyvinylpyrrolidone/hydroxyethyl cellulose/glycerol porous matrices with microspheres made of sodium alginate or pectin and sodium alginate were produced. A surfactant was loaded into these microparticles. The microspheres were characterized using optical microscopy, scanning electron microscopy SEM, and laser diffraction particle size analyzer. For the matrices, the density, porosity, swelling capacity, dissolution in phosphate saline buffer were determined and SEM, mechanical, and thermogravimetric studies were applied. The results showed that the size of the two-component microspheres was slightly larger than that of single-ingredient microparticles. The images confirmed the spherical shape of the microparticles. The prepared matrices had high water uptake ability and porosity due to the presence of hydrophilic polymers. The presence of microparticles in the matrices caused a decrease in these parameters. Degradation of the composites with the microspheres was significantly faster than the matrix without them. The addition of microparticles increased the stiffness and toughness of the prepared materials. The efficiency of the thermal decomposition main stage was reduced in the samples with microspheres, whereas a char residue increased in these composites.

Evaluation of Polymeric Matrix Loaded with Melatonin for Wound Dressing.

The development of scaffolds mimicking the extracellular matrix containing bioactive substances has great potential in tissue engineering and wound healing applications. This study investigates melatonin-a methoxyindole present in almost all biological systems. Melatonin is a bioregulator in terms of its potential clinical importance for future therapies of cutaneous diseases. Mammalian skin is not only a prominent melatonin target, but also produces and rapidly metabolizes the multifunctional methoxyindole to biologically active metabolites. In our methodology, chitosan/collagen (CTS/Coll)-contained biomaterials are blended with melatonin at different doses to fabricate biomimetic hybrid scaffolds. We use rat tail tendon- and Salmo salar fish skin-derived collagens to assess biophysical and cellular properties by (i) Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), (ii) thermogravimetric analysis (TG), (iii) scanning electron microscope (SEM), and (iv) proliferation ratio of cutaneous cells in vitro. Our results indicate that melatonin itself does not negatively affect biophysical properties of melatonin-immobilized hybrid scaffolds, but it induces a pronounced elevation of cell viability within human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF), and reference melanoma cells. These results demonstrate that this indoleamine accelerates re-epithelialization. This delivery is a promising technique for additional explorations in future dermatotherapy and protective skin medicine.

Lyophilized Emulsions in the Form of 3D Porous Matrices as a Novel Material for Topical Application.

Researchers are constantly searching for innovations that can be applied to the cosmetic industry. Production of porous materials stored in a lyophilized form and swollen directly before use may be beneficial considering their facilitated packaging, transport and storage. In this study, we propose porous materials based on sodium alginate, gelatin, glycerol and lipids (cottonseed oil and beeswax) obtained by freeze-drying and cross-linking. Material composition with the most promising properties was modified by the addition of PLA microparticles with Calendula officinalis flower extract. The structure and properties of obtained porous materials were analyzed. ATR-FTIR, mechanical properties, residual moisture content, porosity and density were assessed, as well as swelling properties and degradation after their cross-linking. The loading capacity and in vitro release of Calendula officinalis flower extract were performed for samples with incorporated PLA microparticles containing plant extract. The modification of the composition and fabrication method of materials significantly influenced their physicochemical properties. The selected plant extract was successfully incorporated into polymeric microparticles that were subsequently added into developed materials. Prepared materials may be considered during designing new cosmetic formulations.

Design of Sodium Alginate/Gelatin-Based Emulsion Film Fused with Polylactide Microparticles Charged with Plant Extract.

This study aimed at designing emulsion films based on sodium alginate, gelatin, and glycerol, and their modification by the addition of lipids (cottonseed oil and beeswax). Film composition with the most promising properties was further modified by the incorporation of polylactide (PLA) microparticles with Calendula officinalis flower extract. PLA microspheres were obtained by the emulsion/solvent evaporation method. The size distribution of oily particles in emulsions was investigated. Mechanical properties, moisture content, UV-Vis spectra, and the color of films were analyzed, while biophysical skin parameters were assessed after their application to the skin. Moreover, the contact angles were measured, and the surface free energy of polymeric films was determined. An investigation of the amount of Calendula officinalis flower extract which can be incorporated into PLA microparticles was performed. The modification of the composition of films significantly influenced their physicochemical properties. The selected active ingredient in the form of plant extract was successfully incorporated into polymeric microparticles that were further added into the developed emulsion film. The condition of the skin after the application of obtained emulsion films improved. The prepared materials, especially containing microparticles with plant extract, can be considered for designing new cosmetic forms, such as cosmetic masks, as well as new topical formulations for pharmaceutical delivery.

Arsenic species and their transformation pathways in marine plants. Usefulness of advanced hyphenated techniques HPLC/ICP-MS and UPLC/ESI-MS/MS in arsenic species analysis.

The growing popularity of algae as a foodstuff around the world raises concern for the safety of this food type with respect to arsenic content in algae. The need for determination of total arsenic content and arsenic speciation in algae food has become an important issue. In this paper we have developed a complete analytical procedure for arsenic determination in algae products comprised of 1) total arsenic (tAs) determination in native algae samples after digestion, 2) extraction of As species with the use of two extraction methods with three extracting agents, 3) extracted total arsenic (extracted tAs) determination in algae extracts, 4) bespoke As speciation, 4) mass balance estimation based on extracted tAs and bespoke As speciation results, 5) unknown arsenic (uAs) species identification. Two advanced hyphenated techniques, HPLC/ICP-MS and UPLC/ESI-MS/MS, were employed along with the HPLC/ICP-MS method validation. Total As content in edible algae samples was found to range from (19.28 ± 0.45) mg kg-1 up to (72.6 ± 2.7) mg kg-1. Bespoke arsenic speciation of edible algae samples has revealed the presence of some known inorganic and simple organic As compounds such as As(III) from

Modification of Collagen/Gelatin/Hydroxyethyl Cellulose-Based Materials by Addition of Herbal Extract-Loaded Microspheres Made from Gellan Gum and Xanthan Gum.

Because consumers are nowadays focused on their health and appearance, natural ingredients and their novel delivery systems are one of the most developing fields of pharmacy, medicine, and cosmetics. The main goal of this study was to design, prepare, and characterize composite materials obtained by incorporation of microspheres into the porous polymer materials consisting of collagen, gelatin, and hydroxyethyl cellulose. Microspheres, based on gellan gum and xanthan gum with encapsulated Calendula officinalis flower extract, were produced by two methods: extrusion and emulsification. The release profile of the extract from both types of microspheres was compared. Then, obtained microparticles were incorporated into polymeric materials with a porous structure. This modification had an influence on porosity, density, swelling properties, mechanical properties, and stability of materials. Besides, in vitro tests were performed using mouse fibroblasts. Cell viability was assessed with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The obtained materials, especially with microspheres prepared by emulsion method, can be potentially helpful when designing cosmetic forms because they were made from safely for skin ingredients used in this industry and the herbal extract was successfully encapsulated into microparticles.

Effect of plasticizer and surfactant on the properties of poly(vinyl alcohol)/chitosan films.

The objective of this study was to develop eco-friendly films based on poly(vinyl alcohol) (PVA) and chitosan (CTS) with the addition of plasticizer (glycerol or sorbitol) and surfactant (cocamidopropyl betaine). The properties of the obtained polymeric films were determined by contact angle measurements, attenuated total reflection infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM), mechanical tests, and moisture content analysis. The results indicated that four-component blends had high surface hydrophilicity and surface roughness due to the presence of the surfactant. Glycerol incorporation into PVA/CTS blends resulted in higher flexibility and greater water absorption capacity of the three- and four-component polymeric blends compared with these blends with sorbitol. By contrast, the addition of the surfactant to the materials is essential for their application in personal hygiene products as disposable wipes.

Stability and anti-proliferative properties of biologically active compounds extracted from Cistus L. after sterilization treatments.

The growing interest of oncologists in natural compounds such as polyphenols and flavonoids is encouraging the development of innovative and efficient carriers for the delivery of those drugs. This study examines carboxymethyl chitosan-based microcapsules created by spray drying as a method for delivering biologically active compounds isolated from the Cistus herb. Effects of sterilization and encapsulation on the polyphenol and flavonoid content of Cistus extract were investigated to optimize the production process. Furthermore, in vitro studies were carried out to examine the anticancer properties of sterilized polyphenols and flavonoids on glioblastoma cells isolated from oncological patients. Acquired results show high anticancer potential towards glioblastoma as well as low cytotoxicity towards non-cancer cell lines by the substances in question. Steam sterilization is shown to affect the content of biologically active compounds the least. We demonstrate that the investigated form of drug encapsulation is both efficient and potentially possible to scale up from the viewpoint of the pharmaceutical industry.

Evaluation of Immunoreactivity of Pea (Pisum sativum) Albumins in BALB/c and C57BL/6 Mice.

Green pea (Pisum sativum) is a component of European cuisine; however, an estimated 0.8% of Europeans suffer from allergies to pea proteins. We examined the immunoreactive potential of pea albumins (PA) in BALB/c and C57BL/6 mice. Mice were orally gavaged with PA or glycated pea albumins (G-PA) for 10 consecutive days, in combination with an adjuvant. Both PA and G-PA increased PA-specific serum antibody titers to about 212 for anti-PA IgG, ∼27 for anti-PA IgA, and ∼27.8 for anti-PA IgA in fecal extracts (p < 0.001). On day 42 postexposure, the antibodies titers decreased and were greater in BALB/c compared to C57BL/6 mice (p < 0.05). Distribution of CD4+ and CD8+ T cells in lymphoid tissues presented strain-specific differences. PA was found to induce lymphocyte proliferation; however, G-PA did not. Both PA and G-PA changed CD4+ and CD8+ T cells percentages in some lymphoid tissues; however, this did not impact cytokines production by splenocyte cultures evidenced by the stimulation of Th1, Th2, and Th17 cells. The observed immunomodulatory properties of PA and G-PA and lack of a sign of allergic reaction render them suitable for supplements in personalized diets, but further research is needed to precisely understand this activity.

DFT and spatial confinement: a benchmark study on the structural and electrical properties of hydrogen bonded complexes.

An extended set of 37 exchange correlation functionals, representing different DFT approximations, has been evaluated on a difficult playground represented by the dipole moment (µz), polarizability (αzz), first hyperpolarizability (ßzzz), and the corresponding interaction-induced electrical properties (Δµz, Δαzz, Δßzzz) of spatially confined hydrogen bonded (HB) dimers. A two-dimensional harmonic oscillator potential was used to exert the effect of spatial restriction. The performance of DFT methods in predicting hydrogen bond lengths in the studied molecular complexes upon confinement has also been examined. The data determined using a high-level CCSD(T) method serve as a reference. The conducted analyses allow us to conclude that methods rooted in DFT constitute a precise tool for the calculation of µz and αzz as well as Δµz and Δαzz, as most of the tested functionals provide results affected by rather small relative errors. On the other hand, an accurate description of the nonlinear optical response of the studied HB systems remains a great challenge for most of the analyzed DFT functionals, both in vacuum and in the presence of an analytical confining potential. Some of the tested DFT methods are found to be prone to catastrophic failure in the prediction of ßzzz as well as Δßzzz. The obtained results indicate that there is no great chasm in performance between functionals belonging to different DFT approximations or functionals including different amount of Hartree-Fock exchange when the values of dipole moment and first hyperpolarizability as well as the corresponding interaction-induced electrical properties are considered. However, a higher fraction of Hartree-Fock exchange improves the quality of predictions of αzz and Δαzz. Additionally, it has been shown that only three functionals from the examined set, namely B2PLYP, B3LYP and ωB97X-D, provide highly accurate structural parameters for the investigated systems. Of significant importance is the conclusion that the ωB97X-D functional, representing a modern and highly parametrized range-separated hybrid, demonstrates the most coherent behavior, showing rather small deviations from the reference data in the case of µz, αzz, Δµz and Δαzz as well as the structural parameters of the studied HB dimers. Moreover, our results indicate that the presence of spatial confinement has a rather small effect on the performance of DFT methods.

Microparticles based on natural and synthetic polymers for cosmetic applications.

Most peeling products (exfoliators) available on the market, used in cosmetic and aesthetic dermatology applications, contain synthetic microbeads as abrasive agents. After being released into the natural environment, these non-biodegradable microparticles have an adverse impact on it, especially on aquatic ecosystems. Cosmetics consisting of solid plastic particles will be prohibited in the European Union from 2020. Therefore, there is a great need to develop effective abrasive substances for cosmetic industry. An alternative to synthetic beads may be beads based on biopolymers. Spherical microparticles of sodium alginate and mixture of sodium alginate and starch were obtained using encapsulator BÜCHI B-395 Pro. The obtained microparticles were added to the developed peeling formulation. Subsequently, the evaluation of skin condition after application of peelings with alginate, alginate-starch and synthetic microparticles was made, including topography, skin's barrier quality, hydration, colour, and the level of sebum. The peeling containing sodium alginate and sodium alginate with starch beads does not irritate the skin - redness of skin, itching and dryness did not appear. Microparticles of sodium alginate and sodium alginate with starch act on the skin as effectively as commercial synthetic particles, therefore they may be successfully used as abrasive ingredients in the developed recipe.

Assessment of DFT for endohedral complexes' dipole moment: PNO-LCCSD-F12 as a reference method.

We present a systematic evaluation of the performance of a wide range of exchange-correlation functionals and related dispersion correction schemes for the computation of dipole moments of endohedral complexes, formed through the encapsulation of an AB molecule (AB = LiF, HCl) inside carbon nanotubes (CNTs) of different diameter. The consistency and accuracy of (i) generalized gradient approximation, (ii) meta GGA, (iii) global hybrid, and (iv) range-separated hybrid density functionals are assessed. In total, 37 density functionals are tested. The results obtained using the highly accurate pair natural orbitals based explicitly correlated local coupled cluster singles doubles (PNO-LCCSD-F12) method of Werner and co-workers [Schwilk et al., J. Chem. Theory Comput., 2017, 13, 3650; Ma et al., J. Chem. Theory Comput., 2017, 13, 4871] with the aug-cc-pVTZ basis set serve as a reference. The static electric dipole moment is computed via the finite field response or, when possible, as the expectation value of the dipole operator. Among others, it is shown that functionals belonging to the class of range-separated hybrids, provide results closest to the coupled cluster reference data. In particular, the ωB97X as well as the M11 functional may be considered as a promising choice for computing electric properties of noncovalent endohedral complexes. On the other hand, the worst performance was found for the functionals which do not include the Hartree-Fock exchange. The analysis of both the coupled cluster and the DFT results indicates a strong coupling of dispersion and polarization that may also explain why lower level DFT methods, as well as Hartree-Fock and MP2, cannot yield dipole moments beyond a qualitative agreement with the higher order reference data. Interestingly, the much smaller and less systematically constructed basis sets of Pople of moderate size provide results of accuracy at least comparable with the extended Dunning's aug-cc-pVTZ basis set.

Author Correction: Antimicrobial Peptide Potency is Facilitated by Greater Conformational Flexibility when Binding to Gram-negative Bacterial Inner Membranes.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Collagen/Gelatin/Hydroxyethyl Cellulose Composites Containing Microspheres Based on Collagen and Gelatin: Design and Evaluation.

The objective of this study was to develop three-dimensional collagen/gelatin/hydroxyethyl cellulose composites in combination with gelatin or collagen-gelatin loaded microspheres. Microspheres were prepared by an emulsification/crosslinking method. A 1-Ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) mixture were used as a crosslinking agent for the obtained materials. The structure of the materials was studied using scanning electron microscopy (SEM) and infrared spectroscopy. Moreover, a Calendula officinalis (pot marigold) flower extract release profile of the microsphere-loaded matrices was assessed in vitro. Additionally, porosity, density, stability, swelling and mechanical properties were tested. On the basis of SEM images, the microspheres exhibited a spherical shape and were irregularly dispersed in the polymer matrix. However, it was found that the addition of microparticles to obtained materials did not significantly change their microstructure. We observed a slight decrease in the swelling properties of matrices and an increase in values of Young's modulus. Significantly, the addition of microspheres to the polymer matrices led to improved loading capacity of materials and release performance of Calendula officinalis flower extract. This makes the collagen/gelatin/hydroxyethyl cellulose composites containing microspheres a promising and suitable vehicle for biomedical, dermatological, or cosmetic applications.