Effect of Sex Steroids and PGF2α on the Expression of Their Receptors and Decorin in Bovine Caruncular Epithelial Cells in Early–Mid Pregnancy

Changes in the expression of various genes, including pregnancy-associated hormone receptors and extracellular matrix proteins, have been suggested to play a significant role in bovine placental development. This study aimed to examine the influence of sex steroids and PGF_2α on decorin (DCN) expression in the epithelial cells of bovine caruncle in early–mid pregnancy in cows. The expression patterns of DCN, PTGFR_, PGR and ESR1 were analyzed by RT-qPCR and Western blotting in primary caruncular epithelial cell cultures (PCECC) and placental tissue homogenates derived from the 2nd and 4th months of pregnancy. PCECC were found to express DCN, PTGFR_, PGR and ESR1. The intensity of PGR staining was higher in cells derived from the 4th month of pregnancy (p < 0.05). The 17β-estradiol, progesterone and PGF_2α have not been shown to affect DCN expression. PGF_2α decreased PTGFR expression in cells derived from the 4th month of gestation (p < 0.05). In conclusion, the results of the present preliminary study showed that the expression of the PTGFR, ESR1, PGR and DCN in PCECC does not vary throughout early–mid pregnancy. Further studies should be carried out to observe the relationship between hormonal status and cellular adhesion to determine their importance for properly developing placentation and pregnancy in cows.     

Synthesis and Characterization of New Ruthenium (II) Complexes of Stoichiometry [Ru(p-Cymene)Cl2L] and Their Cytotoxicity against HeLa-Type Cancer Cells

When the [Ru(p-cymene)(μ-Cl)Cl]₂ complex is made to react, in dichloromethane, with the following ligands: 2-aminobenzonitrile (2abn), 4-aminobenzonitrile (4abn), 2-aminopyridine (2ampy) and 4-aminopyridine (4ampy), after addition of hexane, the following compounds are obtained: [Ru(p-cymene)Cl₂(2abn)] (I), [Ru(p-cymene)Cl₂(4abn)] (II), [Ru(p-cymene)Cl₂(2ampy] (III) and [Ru(p-cymene)Cl₂(μ-(4ampy)] (IV). All the compounds are characterized by elemental analysis of carbon, hydrogen and nitrogen, proton nuclear magnetic resonance, COSY ¹H-¹H, high-resolution mass spectrometry (ESI), thermogravimetry and single-crystal X-ray diffraction (the crystal structure of III is reported and compared with the closely related literature of II). The cytotoxicity effects of complexes were described for cervical cancer HeLa cells via 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay. The results demonstrate a low in vitro anticancer potential of the complexes.     

Investigation into the Use of Encorafenib to Develop Potential PROTACs Directed against BRAFV600E Protein

BRAF is a serine/threonine kinase frequently mutated in human cancers. BRAF^V600E mutated protein is targeted through the use of kinase inhibitors which are approved for the treatment of melanoma; however, their long-term efficacy is hampered by resistance mechanisms. The PROTAC-induced degradation of BRAF^V600E has been proposed as an alternative strategy to avoid the onset of resistance. In this study, we designed a series of compounds where the BRAF kinase inhibitor encorafenib was conjugated to pomalidomide through different linkers. The synthesized compounds maintained their ability to inhibit the kinase activity of mutated BRAF with IC₅₀ values in the 40–88 nM range. Selected compounds inhibited BRAF^V600E signaling and cellular proliferation of A375 and Colo205 tumor cell lines. Compounds 10 and 11, the most active of the series, were not able to induce degradation of mutated BRAF. Docking and molecular dynamic studies, conducted in comparison with the efficient BRAF degrader P5B, suggest that a different orientation of the linker bearing the pomalidomide substructure, together with a decreased mobility of the solvent-exposed part of the conjugates, could explain this behavior.     

The Genus Cetraria s. str.—A Review of Its Botany,Phytochemistry, Traditional Uses and Pharmacology

The genus Cetraria s. str. (Parmeliaceae family, Cetrarioid clade) consists of 15 species of mostly erect brown or greenish yellow fruticose or subfoliose thallus. These Cetraria species have a cosmopolitan distribution, being primarily located in the Northern Hemisphere, in North America and in the Eurasia area. Phytochemical analysis has demonstrated the presence of dibenzofuran derivatives (usnic acid), depsidones (fumarprotocetraric and protocetraric acids) and fatty acids (lichesterinic and protolichesterinic acids). The species of Cetraria, and more particularly Cetraria islandica, has been widely employed in folk medicine for the treatment of digestive and respiratory diseases as decoctions, tinctures, aqueous extract, and infusions. Moreover, Cetraria islandica has had an important nutritional and cosmetic value. These traditional uses have been validated in in vitro and in vivo pharmacological studies. Additionally, new therapeutic activities are being investigated, such as antioxidant, immunomodulatory, cytotoxic, genotoxic and antigenotoxic. Among all Cetraria species, the most investigated by far has been Cetraria islandica, followed by Cetraria pinastri and Cetraria aculeata. The aim of the current review is to update all the knowledge about the genus Cetraria covering aspects that include taxonomy and phylogeny, morphology and distribution, ecological and environmental interest, phytochemistry, traditional uses and pharmacological properties.     

Metabolic Profile of Agropyron repens (L.) P. Beauv. Rhizome Herbal Tea by HPLC-PDA-ESI-MS/MS Analysis

Agropyron repens (L.) P. Beauv. (couch grass) is a world-wide infesting rhizomatous plant with pharmacological applications. Chemical research is focused on its allelopathic and anti-inflammatory components, which are mainly present in the essential oil. Conversely, the aqueous extracts have been sparingly investigated, although the herbal tea is by far the most used formulation. To fill the gap, the metabolic profile of Agropyron repens rhizome herbal tea was investigated by electrospray ionization (ESI) tandem–mass spectrometry (MS/MS); the phenolic profile was investigated by HPLC-PDA-ESI-MS/MS. ESI-MS fingerprinting was provided, evidencing diagnostic ions for saccharides, organic acids and amino acids. The HPLC-PDA-ESI-MS/MS analysis evidenced at least 20 characteristic phenolic compounds, the most representative being caffeoyl and feruloyl quinic esters, followed by coumaric, caffeic and ferulic acids, and hesperidin among flavonoids. In addition, the essential amino acid tryptophan was identified for the first time. The results suggest new perspectives of applications for Agropyron repens rhizome.     

Biomaterials Based on Chitosan and Its Derivatives and Their Potential in Tissue Engineering and Other Biomedical Applications—A Review

In the times of dynamically developing regenerative medicine, more and more attention is focused on the use of natural polymers. This is due to their high biocompatibility and biodegradability without the production of toxic compounds, which means that they do not hurt humans and the natural environment. Chitosan and its derivatives are polymers made most often from the shells of crustaceans and are biodegradable and biocompatible. Some of them have antibacterial or metal-chelating properties. This review article presents the development of biomaterials based on chitosan and its derivatives used in regenerative medicine, such as a dressing or graft of soft tissues or bones. Various examples of preparations based on chitosan and its derivatives in the form of gels, films, and 3D structures and crosslinking products with another polymer are discussed herein. This article summarizes the latest advances in medicine with the use of biomaterials based on chitosan and its derivatives and provides perspectives on future research activities.     

Azapeptide activity-based probes for the SARS-CoV-2 main protease enable visualization of inhibition in infected cells

The COVID-19 pandemic has revealed the vulnerability of the modern, global society. With expected waves of future infections by SARS-CoV-2, treatment options for infected individuals will be crucial in order to decrease mortality and hospitalizations. The SARS-CoV-2 main protease is a validated drug target, for which the first inhibitor has been approved for use in patients. To facilitate future work on this drug target, we designed a solid-phase synthesis route towards azapeptide activity-based probes that are capped with a cysteine-reactive electrophile for covalent modification of the active site of M^pro. This design led to the most potent ABP for M^pro and one of the most potent inhibitors reported thus far. We demonstrate that this ABP can be used to visualize M^pro activity and target engagement by drugs in infected cells.

The COVID-19 pandemic has revealed the vulnerability of the modern, global society.     

Bimetallic TiO2 Nanoparticles for Lignin-Based Model Compounds Valorization by Integrating an Optocatalytic Flow-Microreactor

The challenge of improving the activity of TiO₂ by modifying it with metals and using it for targeted applications in microreactor environments is an active area of research. Recently, microreactors have emerged as successful candidates for many photocatalytic reactions, especially for the selective oxidation process. The current work introduces ultrasound-assisted catalyst deposition on the inner walls of a perfluoro-alkoxy alkane (PFA) microtube under mild conditions. We report Cu-Au/TiO₂ and Fe-Au/TiO₂ nanoparticles synthesized using the sol–gel method. The obtained photocatalysts were thoroughly characterized by UV–Vis diffuse-reflectance spectroscopy (DRS), high-resolution scanning electron microscopy (HR-SEM), high-resolution transmission electron microscopy (HR-TEM), X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and N₂ physisorption. The photocatalytic activity under UV (375 nm) and visible light (515 nm) was estimated by the oxidation of lignin-based model aromatic alcohols in batch and fluoropolymer-based flow systems. The bimetallic catalyst exhibited improved photocatalytic selective oxidation. Herein, four aromatic alcohols were individually investigated and compared. In our experiments, the alcohols containing hydroxy and methoxy groups (coniferyl and vanillin alcohol) showed high conversion (93% and 52%, respectively) with 8% and 17% selectivity towards their respective aldehydes, with the formation of other side products. The results offer an insight into ligand-to-metal charge transfer (LMCT) complex formation, which was found to be the main reason for the activity of synthesized catalysts under visible light.     

HeH+ under Spatial Confinement

In the present study, the influence of spatial confinement on the bond length as well as dipole moment, polarizability and (hyper)polarizabilities of HeH+ ion was analyzed. The effect of spatial confinement was modelled by cylindrically symmetric harmonic oscillator potential, that can be used to mimic high pressure conditions. Based on the conducted research it was found that the spatial confinement significantly affects the investigated properties. Increasing the confinement strength leads to a substantial decrease of their values. This work may be of particular interest for astrochemistry as HeH+ is believed to be the first compound to form in the Universe.     

Identification of Human Dihydroorotate Dehydrogenase Inhibitor by a Pharmacophore-Based Virtual Screening Study

Human dihydroorotate dehydrogenase (hDHODH) is an enzyme belonging to a flavin mononucleotide (FMN)-dependent family involved in de novo pyrimidine biosynthesis, a key biological pathway for highly proliferating cancer cells and pathogens. In fact, hDHODH proved to be a promising therapeutic target for the treatment of acute myelogenous leukemia, multiple myeloma, and viral and bacterial infections; therefore, the identification of novel hDHODH ligands represents a hot topic in medicinal chemistry. In this work, we reported a virtual screening study for the identification of new promising hDHODH inhibitors. A pharmacophore-based approach combined with a consensus docking analysis and molecular dynamics simulations was applied to screen a large database of commercial compounds. The whole virtual screening protocol allowed for the identification of a novel compound that is endowed with promising inhibitory activity against hDHODH and is structurally different from known ligands. These results validated the reliability of the in silico workflow and provided a valuable starting point for hit-to-lead and future lead optimization studies aimed at the development of new potent hDHODH inhibitors.