Cancer is a disease caused by the alteration of proto-oncogenes and tumor suppressor genes, which has a high prevalence in the population and is one of the main causes of death worldwide. For its treatment, there are different therapy options, but these are not always effective for all existing types of cancer, which gives rise to the search for new compounds. The objective of the work is to determine the degree of cytotoxic activity of naphthoxyacetamide using dose-response curves in a cell viability assay. For this, the cytotoxic effects of N-(2-morpholinoethyl)-2-(naphthalen-2-yloxy) were identified in cancer cells (HeLa) based on the metabolic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylretrazol (MTT) bromide. The cell cultures were seeded at a density of 5,000 cells/well in 96-well plates and treated by hexapplication with various concen-trations of the compounds to be tested (0.31-3.16 µM/mL) for 24 h. Microplates were read in an ELISA reader at 575nm. The dose response curve of N- (2-morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide (3.16, 1.77, 1, 0.31 µM/mL). The results showed that N-(2-morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide, at a concentration of 3.16 µM/ mL, presents cytotoxic effects similar to those shown by the drug reference (cisplatin 3.32 µM/mL). In conclusion, N-(2-morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide showed cyto-toxic effects similar to Cisplatin.

Scrophularia striata Boiss. (Scrophulariaceae family), as an important medicinal plant, is one of the species native to western Iran. This perennial herbaceous plant has been traditionally used to cure various diseases, including eye and ear infections, inflammation, infectious wounds, colds, and boils, and is also used to treat bacterial, fungal, and viral infections in the world. Since the COVID-19 pandemic outbreak, Ongoing efforts are proceeding worldwide to develop an efficient vaccine and use approaches to find preventive measures and effective treatment. S. striata was introduced as a phenylethanoid glycosides (PhGs) source. S. striata functions as a resistant plant under various stresses. The essential mechanism in response to abiotic and biotic stress is the production of phenolic compound precursors, which eventually leads to PhG compound accumulation, especially acteoside, in this plant. Acteoside operates as a powerful antioxidant that scavenges excess ROS content in biological systems. The study purposed to evaluate the acteoside content in response to Pb stress of S. striata. HPLC analysis was employed to identify PhGs between the untreated and Pb-treated shoots plants with three gathering times (24, 48, and 72 hours). Our results indicated that acteoside increased significantly after 72h under Pb stress, and no significant difference was observed in other time courses. In general, S. striata is a good source of PhGs, especially acteoside, with application in the pharmaceutical industry.

The innate immune system is responsible for the body's defense against aggressive agents, mainly through activating pattern-recognition receptors (PRRs). Recognizing these agents results in an inflammatory response that activates tissue repair and eliminating the agent. Among the macromolecules related to these events are inflammasomes (inflammatory response activators), with emphasis on nucleotide-binding domain leucine-rich repeat-containing receptors protein 3 (NLRP3), in which blocking their oligomerization inhibits inflammasome activity. In this way, targeting NLRP3 represents a new approach to designing anti-inflammatory drugs. Here, molecular docking and dynamics, focusing on Dynamic Cross-Correlation Matrix (DCCM) analysis, were used to characterize significant interactions of MCC950 (known inhibitors) and their analog NP3-166 (ligand co-crystalized) with NLRP3 and generate useful information in drug design. The results showed that the compounds were stable during the MD simulation time (100 ns), demonstrated by the RMSD RMSF, R_g, SASA, and H-bond plots. Analysis of the DCCM graphs showed that more correlated movements are presented for MCC950 compared to NP3-166. In fact, the more rigid structure of MCC950 may influence the more significant interaction. A higher correlation observed in both complexes between residues 100 – 200 and 300 – 400 highlights the results obtained from the interaction analysis, showing that interaction with Ala²²⁸ and Arg⁵⁷⁸ may be essential for the inhibitory activity of the compounds. Our findings highlight that greater structural rigidity of the ligand and interactions with residues Ala²²⁸ and Arg⁵⁷⁸ may be critical for designing new NLRP3 inhibitors with anti-inflammatory potential.

Currently, there is a growing interest in the development of bimodal systems that have a signal for more than one diagnostic imaging technique, such as magnetic resonance imaging (MRI). MRI is able to distinguish pathological from healthy tissues, however, in some cases, a high local concentration of the contrast agents (CAs) is necessary to improve the contrast in the images. Nanoparticulate CAs are able to concentrate several CAs molecules into one nanoparticle, increasing the local concentration of paramagnetic ions. In this work, we intend to associate AgInSe2 quantum dots (QDs) with gadolinium complexes (DOTA-Gd) to develop bimodal systems. The QDs were prepared in water and the synthesis parameters were optimized. The ligand DOTA was conjugated with cysteamine and complexed with Gd3+. The complex was then conjugated to QDs through the metal-thiol bond, obtaining the bimodal systems. Optical characterization indicated that the QDs remained stable and fluorescent, and an increase in emission intensity after conjugation was observed. The systems were characterized by relaxometry at 20MHz and 37 °C, obtaining longitudinal relaxivities by Gd3+ higher than the CAs used clinically. Thus, the prepared nanoprobes showed promising properties for MRI and optical imaging.

Immunohistochemical staining of cell and molecular targets in brain samples is a powerful tool that can provide valuable information on neurological mechanisms. However, post-processing of microphotographs acquired after 3, 3’-Diaminobenzidine (DAB) staining can be particularly challenging due to the complexity, size and number of the samples, the targets being analyzed, image quality, and even the subjectivity related with image analysis and morphological appreciation by different users. Conventional analysis of these data usually relies on the manual quantification of distinct parameters in a large set of images like, for example, the number and size of cells or, in more complex analysis, the number and size of cell branching (as in Sholl analysis, e.g.). These prove to be extremely time-consuming and complex tasks, inappropriate for the processing of high amounts of information.

Here we describe an improved semi-automatic method to quantify glial fibrillary acidic protein (GFAP)-labelled astrocytes in immunohistochemistry images of rat brain, at a magnification as low as 20x. This method is a straightforward adaptation of the Young & Morrison method, using the ImageJ plugin Skeletonize, coupled to an intuitive data processing in datasheet-based software.

This method allows a faster and more efficient post-processing of brain tissue samples for the quantification of astrocytes size and number, area occupied, as well as astrocyte branching and branch length (indicative of astrocyte activation). Thus, contributing to better understand the possible inflammatory response developed by astrocytes.

Lignocellulosic biomass can become an important raw material for the production of polymers containing sugars. Glucose is the best known breakdown product of cellulose. However, the depolymerization of hemicellulose results in the formation of glucose, as well as other hexoses (mannose, galactose, rhamnose) or pentoses (xylose, arabinose). On the other hand, levulinic acid has been pointed out as a promising molecule with regard to sustainable chemicals, which can be produced from renewable resources such as lignocellulosic biomass. The α-angelica lactone (AL) can, in turn, be produced from levulinic acid through an intramolecular condensation process followed by dehydration, presenting itself as an important raw material for the synthesis of new polymers sustainable. This work has as main objective to investigate the valorization of sugars and their derivatives, present as major components in the aqueous fraction resulting from the liquefaction processes of the wood biomass, aiming at its use in the production of sustainable and biodegradable polymers, which can be applied to processes industrial in the pharmaceutical industry.

Objective: Sialidases can play an important role in atherosclerosis development due to modification of low-density lipoproteins (LDL). It is known that desialylated LDL are associated with atherosclerosis development. However, the information about factors leading to desialylation of LDL needs in clarifying. The creation of appropriate model object could help to understand factors related to desialylation of LDL. The aim of this study was to test the possibility to change sialylation of lipoproteins in healthy mice upon an injection of immobilized sialidase.

Methods: The control group of C57BL6 mice (n=48) was treated by a single injection of saline, while the experimental group (n=48) received Vibrio cholerae sialidase conjugated with mouse IgG. Mice were terminated at fixed periods: before and after a single injection (1-7 days). LDL was isolated from serum by ultracentrifugation. The content of sialic acid was determined according to Warren’s method. Lipids of serum were measured by commercial kits.

Results: A significant decrease in LDL sialic acid by 30% was detected up to 5 days after the sialidase injection. Also, serum levels of triglycerides, total cholesterol and HDL-cholesterol in experimental mice did not differ compared with wild-type control mice.

Conclusions: A new approach to study the role of sialidase as a proatherogenic factor in vivo was established. Research was supported by the Russian Science Foundation (grant#20-15-00264).

Schinus molle is a perennial tree commonly known as "Pirul" in Mexico. This aromatic plant belongs to the Anacardiaceae family and the antibacterial, antifungal, insecticidal and cytotoxic activities of its bioactive essential oils have been investigated. Locally, the plant is mainly used as an analgesic, antiseptic, antibacterial, purgative, and diuretic agent. In the study, the plant, which is generally grown as an ornamental plant on the Mediterranean coasts of Turkey, was evaluated in terms of its cytotoxic properties based on its secondary metabolites. Raw and ripe fruits, together with the plant's leaves, were collected and extracted using different solvents. Both 70% methanol and water extracts of leaves, ripe fruits, and raw fruits were prepared. The 6 different extracts obtained were tested in cell lines of humans' most common cancer types (Du-145 prostate cancer, CaCo-2 colon cancer, and MCF-7 breast cancer). As a result, methanol extracts prepared from the ripe fruits of the plant decreased the viability of three different cancer cells, especially MCF-7 and Du-145 cell lines, at low concentrations below 50%. Especially in the MCF-7 cell line, the viability at 15 µg/mL was calculated as 46.03±1.19%. While the cell line with the most minor effect of the extracts was CaCo-2, the extracts with the most negligible antiproliferative effect were the water extracts of the leaves, raw, and ripe fruits.

Rare earth-doped nanoparticles have been investigated for their use in disease diagnosis, drug delivery, tumor therapy and bioimaging. In this context, we selected BaSO4:Eu phosphor nanoparticles, commercially available by Merck, to evaluate their antitumoral efficiency for prospective therapeutic applications, as no study was previously performed. Lung carcinoma epithelial cells (A549 cell line) were incubated with these barite (BaSO4) nanophosphors up to 72 hours. The highest concentration tested (200 µg/mL nanoparticles) decreased the number of viable cells only by 10% from control as measured by MTT test. This result was also confirmed by double staining of viable and dead cells with calcein AM and ethidium homodimer, respectively. In addition, the level of nitric oxide released by cells in the media after the incubation with the nanoparticles increased with 10% above control, showing that no major inflammation was induced, even in the presence of high concentrations of particles. However, an increased accumulation of lysosomes was noticed by LysoTracker Green DND-26 in a time- and dose-dependent manner. This finding could suggest the uptake of Eu-doped barite particles in these acidic organelles in order to be eliminated further by the cells. In conclusion, our investigation revealed no significant anti-proliferative properties of the BaSO4:Eu phosphor nanoparticles on lung tumor cells, but further investigations related to their cytotoxicity should be performed for a better characterization in a biological environment. Acknowledgements: This research was funded by UEFISCDI, grant number PN-III-P1-1_1-TE-2021-1375 (81TE/2022).

Thiazolopyrimidines are well known to be designed to act as bio-isosteric analogues of purine nucleus. They proved to show a wide range of biological activities; such as anticancer, anti-inflammatory, antifungal, antiviral and antitubercular activity. In this study, a literature survey was thoroughly performed to elect the most active thiazolopyrimidine-containing scaffolds; acting as anticancer agents; to be subjected to extensive computational studies in order to explore the possible credible mode of their anticancer activity. First, drug-likeness was investigated for the most active derivatives, followed by molecular docking study against CDK, VEGFR and PI3K enzymes to assess their binding energy and propose the mode of action. Then, contact preference and surface mapping studies were carried out to explain the presence of remarkable affinity of certain analogues towards a specific enzyme, in addition to providing more information about their activity. Finally, physicochemical properties, Lipinski's rule of five and ADMET prediction studies were applied to predict the best route of administration and to suggest the pharmacokinetics of the most promising candidates.