Mesoporous Composite Bioactive Compound Delivery System for Wound-Healing Processes.

Currently, the treatment of wounds is still a challenge for healthcare professionals due to high complication incidences and social impacts, and the development of biocompatible and efficient medicines remains a goal. In this regard, mesoporous materials loaded with bioactive compounds from natural extracts have a high potential for wound treatment due to their nontoxicity, high loading capacity and slow drug release. MCM-41-type mesoporous material was synthesized by using sodium trisilicate as a silica source at room temperature and normal pressure. The synthesized mesoporous silica was characterized by using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), N2 absorption-desorption (BET), Dynamic Light Scattering (DLS) and Fourier transform infrared spectroscopy (FT-IR), revealing a high surface area (BET, 1244 m2/g); pore diameter of approx. 2 nm; and a homogenous, ordered and hexagonal geometry (TEM images). Qualitative monitoring of the desorption degree of the Salvia officinalis (SO) extract, rich in ursolic acid and oleanolic acid, and Calendula officinalis (CO) extract, rich in polyphenols and flavones, was performed via the continuous recording of the UV-VIS spectra at predetermined intervals. The active ingredients in the new composite MCM-41/sage and marigold (MCM-41/SO&CO) were quantified by using HPLC-DAD and LC-MS-MS techniques. The evaluation of the biological composites' activity on the wound site was performed on two cell lines, HS27 and HaCaT, naturally involved in tissue-regeneration processes. The experimental results revealed the ability to stimulate collagen biosynthesis, the enzymatic activity of the main metalloproteinases (MMP-2 and MMP-9) involved in tissue remodeling processes and the migration rate in the wound site, thus providing insights into the re-epithelializing properties of mesoporous composites.

Implications of the Cultivation of Rosemary and Thyme (Lamiaceae) in Plant Communities for the Development of Antioxidant Therapies.

Oxidative stress is the most critical factor in multiple functional disorders' development, and natural antioxidants could protect the human body against it. Our study aims to investigate the polyphenol content of four extracts of two medicinal plants (Rosmarinus officinalis L. and Thymus vulgaris L.) and analyze the correlation with their antioxidant activity. The research was carried out on extracts of rosemary and thyme obtained from species cultivated together in plant communities. Both were compared with extracts from species cultivated in individual crops (control crops). Their polyphenols were determined by spectrophotometric methods (dosage of flavones, phenol carboxylic acids, and total polyphenols) and chromatography (UHPLC-MS and FT-ICR MS). Triterpenic acids were also quantified, having a higher concentration in the thyme extract from the culture. The antioxidant activity of the dry extracts was evaluated in vitro (DPPH, ABTS, and FRAP) and in silico (prediction of interactions with BACH1/BACH2 transcription factors). The concentrations of polyphenols are higher in the extracts obtained from the sources collected from the common crops. These observations were also validated following the chromatographic analysis for some compounds. Statistically significant differences in the increase in the antioxidant effect were observed for the extracts from the common batches compared to those from the individual ones. Following the Pearson analysis, the IC50 values for each plant extract were strongly correlated with the concentration of active phytoconstituents. Molecular docking studies revealed that quercetin could bind to BTB domains of BACH1 and BACH2 transcription factors, likely translating into increased antioxidant enzyme expression. Future studies must validate the in silico findings and further investigate phytosociological cultivation's effects.

Phytochemical Screening and Antioxidant Potential of Selected Extracts from Betula alba var. pendula Roth., Glycyrrhiza glabra L., and Avena sativa L.

The aim of the present study was to obtain, characterize, and evaluate the antioxidant potential of some extracts obtained from the bark of Betula alba var. pendula Roth., the root of Glycyrrhiza glabra L., and the green herb of the Avena sativa. The results revealed that the lowest IC50 value, determined by all three methods, was obtained for Betulae extractum (BE) (73.6 µg/mL-DPPH method, 11.2 µg/mL-ABTS method, and 58.7 µg/mL-FRAP method), followed by Liquiritiae extractum (LE) (805.6 µg/mL, 92.1 µg/mL, and 722 µg/mL) and Avenae extractum (1.13 mg/mL-DPPH method, 99.7 µg/mL-ABTS method, and 135.1 µg/mL-FRAP method). These results correlate with total polyphenols content (expressed in g tannic acid/100 g dry extract), with BE having more polyphenols than LE and AE (47.96 ± 9.7083 for BE, compared with 9.31 ± 0.9913 for LE and 40.55 ± 6.3715 for AE). The total flavonoid content (expressed as g rutoside/100 g dry extract) is similar for BE and LE (3.75 ± 0.3140 and 3.44 ± 0.3037) and smaller for AE (1.95 ± 0.0526). Therefore, Betulae extractum has the strongest antioxidant action, with an IC50 value very close to the standard used as a reference (ascorbic acid-16.5 µg/mL solution). The FT-ICR-MS analysis confirmed the presence of the major compounds in all three extracts. The antioxidant properties of the studied extracts were further supported by molecular docking experiments that revealed the potential of the analyzed phytochemicals to act as both noncovalent and covalent activators of the Nrf2 signaling pathway, with promising benefits in treating various skin disorders.

Outlook on Chronic Venous Disease Treatment: Phytochemical Screening, In Vitro Antioxidant Activity and In Silico Studies for Three Vegetal Extracts.

Chronic venous disease is one of the most common vascular diseases; the signs and symptoms are varied and are often neglected in the early stages. Vascular damage is based on proinflammatory, prothrombotic, prooxidant activity and increased expression of several matrix metalloproteinases (MMPs). The aim of this research is preparation and preliminary characterization of three vegetal extracts (Sophorae flos-SE, Ginkgo bilobae folium-GE and Calendulae flos-CE). The obtained dry extracts were subjected to phytochemical screening (FT-ICR-MS, UHPLC-HRMS/MS) and quantitative analysis (UHPLC-HRMS/MS, spectrophotometric methods). Antioxidant activity was evaluated using three methods: FRAP, DPPH and ABTS. More than 30 compounds were found in each extract. The amount of flavones follows the succession: SE > GE > CE; the amount of phenolcarboxylic acids follows: SE > CE > GE; and the amount of polyphenols follows: SE > GE > CE. Results for FRAP method varied as follows: SE > CE > GE; results for the DPPH method followed: SE > GE > CE; and results for ABTS followed: SE > GE > CE. Strong and very strong correlations (appreciated by Pearson coefficient) have been observed between antioxidant activity and the chemical content of extracts. Molecular docking studies revealed the potential of several identified phytochemicals to inhibit the activity of four MMP isoforms. In conclusion, these three extracts have potential in the treatment of chronic venous disease, based on their phytochemical composition.

Snapshot of the pollution-driven metabolic and microbiota changes in Carassius gibelio from Bucharest leisure lakes.

In the last decades, increased intakes of contaminants and the habitats' destruction have produced drastic changes in the aquatic ecosystems. The environmental contaminants can accumulate in aquatic organisms, leading to the disturbance of the antioxidant/prooxidant balance in fish. In this context, we evaluated the level of organic, inorganic and microbiological pollutants in four leisure lakes (Chitila, Floreasca, Tei and Vacaresti) from Bucharest, the largest city of Romania, in order to compare their effects on hepatopancreas and gills metabolism and antioxidant defense mechanisms in Carassius gibelio, the most known and widespread freshwater fish in this country. The lowest level of oxidative stress was recorded in the case of fish collected from the Vacaresti lake, a protected wetland area where aquatic organisms live in wild environmental conditions. In contrast, significant oxidative changes were observed in the hepatopancreas and gills of fish from the Chitila, Floreasca and Tei lakes, such as reduced glutathione S-transferase activity and glutathione level, and increased degree of lipid peroxidation, being correlated with elevated levels of pesticides (such as 2,4'-methoxychlor) and Escherichia coli load in these organs. Although different patterns of pollutants' accumulation were observed, no important interindividual variations in cytosine methylation degree were determined. In conclusion, the presence and concentrations of metals, pesticides and antibiotics varied with the analyzed tissue and sampling site, and were correlated with changes in the cellular redox homeostasis, but without significantly affecting the epigenetic mechanisms.

The Influence of Phytosociological Cultivation and Fertilization on Polyphenolic Content of Menthae and Melissae folium and Evaluation of Antioxidant Properties through In Vitro and In Silico Methods.

Since medicinal plants are widely used in treating various diseases, phytoconstituents enrichment strategies are of high interest for plant growers. First of all, we investigated the impact of phytosociological cultivation on polyphenolic content (total flavonoids-TFL, and total polyphenols-TPC) of peppermint (Mentha piperita L.) and lemon balm (Melissa officinalis L.) leaves, using spectrophotometric methods. Secondly, the influence of chemical (NPK) and organic (BIO) fertilization on polyphenolic content and plant material quality was also assessed. Dry extracts were obtained from harvested leaves using hydroethanolic extraction solvents for further qualitative and quantitative assessment of phytoconstituents by FT-ICR MS and UHPLC-MS. Furthermore, the antioxidant activity of leaf extracts was determined in vitro using DPPH, ABTS and FRAP methods. Molecular docking simulations were employed to further evaluate the antioxidant potential of obtained extracts, predicting the interactions of identified phytochemicals with sirtuins. The concentration of polyphenols was higher in the plant material harvested from the phytosociological culture. Moreover, the use of BIO fertilizer led to the biosynthesis of a higher content of polyphenols. Higher amounts of phytochemicals, such as caffeic acid, were determined in extracts obtained from phytosociological crops. The antioxidant activity was dependent on polyphenols concentration, more potent inhibition values being observed for the extracts obtained from the phytosociological batches. Molecular docking studies and MM/PBSA calculations revealed that the obtained extracts have the potential to directly activate sirtuins 1, 5 and 6 through several polyphenolic compounds, such as rosmarinic acid, thus complementing the free radical scavenging activity with the potential stimulation of endogenous antioxidant defense mechanisms. In conclusion, growing medicinal plants in phytosociological cultures treated with biofertilizers can have a positive impact on plant material quality, concentration in active constituents and biological activity.

Novel Graphene Oxide/Quercetin and Graphene Oxide/Juglone Nanostructured Platforms as Effective Drug Delivery Systems with Biomedical Applications.

In this paper, novel drug delivery systems (DDS) were designed based on graphene oxide (GO) as nanocarrier, loaded with two natural substances (quercetin (Qu) and juglone (Ju)) at different concentrations. The chemical structure and morphology of the synthesized GO-based materials were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and Raman spectroscopy. The antibacterial activity was evaluated against standard strains, Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739, and Candida albicans ATCC 10231. Results demonstrated excellent antimicrobial activity, with a 5 log reduction of E. coli and a 1 log to 3.04 log reduction of S. aureus populations. Reduction rates were above 90%. Biocompatibility tests were also performed on GO-based materials, and the results showed biocompatible behavior for both L929 fibroblast cell line and BT474 breast cancer cells at lower concentrations. The identity of Qu and Ju was demonstrated by matrix-assisted laser desorption/ionization (MALDI) analysis, showing the compounds' mass with high accuracy. In addition, specific properties of GO made it a versatile matrix for the MALDI analysis. The results of this study indicated that GO-based platforms may be suitable for applications in many areas for the effective and beneficial use of hydrophobic compounds such as Ju and Qu.

Phenotypic Switching of B16F10 Melanoma Cells as a Stress Adaptation Response to Fe3O4/Salicylic Acid Nanoparticle Therapy.

Melanoma is a melanocyte-derived skin cancer that has a high heterogeneity due to its phenotypic plasticity, a trait that may explain its ability to survive in the case of physical or molecular aggression and to develop resistance to therapy. Therefore, the therapy modulation of phenotypic switching in combination with other treatment modalities could become a common approach in any future therapeutic strategy. In this paper, we used the syngeneic model of B16F10 melanoma implanted in C57BL/6 mice to evaluate the phenotypic changes in melanoma induced by therapy with iron oxide nanoparticles functionalized with salicylic acid (SaIONs). The results of this study showed that the oral administration of the SaIONs aqueous dispersion was followed by phenotypic switching to highly pigmented cells in B16F10 melanoma through a cytotoxicity-induced cell selection mechanism. The hyperpigmentation of melanoma cells by the intra- or extracellular accumulation of melanic pigment deposits was another consequence of the SaIONs therapy. Additional studies are needed to assess the reversibility of SaIONs-induced phenotypic switching and the impact of tumor hyperpigmentation on B16F10 melanoma's progression and metastasis abilities.

Magnetic nanoparticles-based therapy for malignant mesothelioma.

This work was aimed to analyze the versatility of the chick embryo chorioallantoic membrane (CAM) as in vivo model for the study of the malignant pleural mesothelioma (MPM) and the therapeutic potential of Fe3O4÷salicylic acid magnetic nanoparticles (SaMNPs) on MPM cells. The antitumor effects of SaMNPs were studied by in vitro and in vivo tests on CARM-L12 TG3 rat malignant mesothelioma cells and human MPM xenografts implanted on CAMs. In order to assess the human MPM xenograft growth characteristics, calretinin, HBME-1 (Hector Battifora mesothelial epitope-1), and cytokeratins immunohistochemical stainings were performed. The human MPM xenografts continue to develop on the CAMs and xenograft MPM cells showed highly metastatic features and a particular pattern of metastasis. The SaMNPs had a specific uptake by the MPM cells and an antiproliferative effect at therapeutic doses greater than 100 µg÷mL. The results confirmed the possibility to use the CAM as in vivo model to study the biology of MPM and to evaluate the antitumor potential of new therapeutic agents. They highlighted a strong antitumor effect of the SaMNPs on the rat and human MPM cells and open new perspectives in the treatment of MPM.

Antitumoral materials with regenerative function obtained using a layer-by-layer technique.

A layer-by layer technique was successfully used to obtain collagen/hydroxyapatite-magnetite-cisplatin (COLL/HAn-Fe3O4-CisPt, n=1-7) composite materials with a variable content of hydroxyapatite intended for use in the treatment of bone cancer. The main advantages of this system are the possibility of controlling the rate of delivery of cytostatic agents, the presence of collagen and hydroxyapatite to ensure more rapid healing of the injured bone tissue, and the potential for magnetite to be a passive antitumoral component that can be activated when an appropriate external electromagnetic field is applied. In vitro cytotoxicity assays performed on the COLL/HAn-Fe3O4-CisPt materials obtained using a layer-by layer method confirmed their antitumoral activity. Samples with a higher content of hydroxyapatite had more antitumoral activity because of their better absorption of cisplatin and consequently a higher amount of cisplatin being present in the matrices.

Hybrid nanomaterial for stabilizing the antibiofilm activity of Eugenia carryophyllata essential oil.

The aim of the present study was to demonstrate that Fe(3)O(4)/oleic acid core/shell nanostructures could be used as systems for stabilizing the Eugenia carryophyllata essential oil (EO) on catheter surface pellicles, in order to improve their resistance to fungal colonization. EO microwave assisted extraction was performed in a Neo-Clevenger (related) device and its chemical composition was settled by GC-MS analysis. Fe(3)O(4)/oleic acid-core/shell nanoparticles (NP) were obtained by a precipitation method under microwave condition. High resolution transmission electron microscopy (HR-TEM) was used as a primary characterization method. The NPs were processed to achieve a core/shell/EO coated-shell nanosystem further used for coating the inner surface of central venous catheter samples. The tested fungal strains have been recently isolated from different clinical specimens. The biofilm architecture was assessed by confocal laser scanning microscopy (CLSM). Our results claim the usage of hybrid nanomaterial (core/shell/coated-shell) for the stabilization of E. carryophyllata EO, which prevented or inhibited the fungal biofilm development on the functionalized catheter, highlighting the opportunity of using these nanosystems to obtain improved, anti-biofilm coatings for biomedical applications.

Synthesis, characterization and in vitro assessment of the magnetic chitosan-carboxymethylcellulose biocomposite interactions with the prokaryotic and eukaryotic cells.

Preparation and characterization of CS/Fe(3)O(4)/CMC composite scaffolds including the morphology, crystallinity, and the in vitro efficacy as antibiotic delivery vehicles as well as their influence on the eukaryotic cells are reported. The results demonstrated that the magnetic polymeric composite scaffolds are exhibiting structural and functional properties that recommend them for further applications in the biomedical field. They improve the activity of currently used antibiotics belonging to penicillins, macrolides, aminoglycosides, rifampicines and quinolones classes, representing potential macromolecular carriers for these antimicrobial substances, to achieve extracellular and intracellular targets. The obtained systems are not cytotoxic and do not influence the eukaryotic HCT8 cell cycle, representing potential tools for the delivery of drugs in a safe, effective and less expensive manner.