Development of Cyclodextrin-Based Mono and Dual Encapsulated Powders by Spray Drying for Successful Preservation of Everlasting Flower Extract.

The study aimed to develop encapsulation systems to maintain the preservation of everlasting (Helichrysum plicatum) flower extract polyphenols. Spray-dried encapsulates were formulated using ß-cyclodextrin (BCD) and 2-hydroxypropyl-ß-cyclodextrin (HPBCD) as supramolecular hosts, and their macromolecule mixtures with the conventional carriers, maltodextrin (MD) and whey protein (WP). The obtained microparticles were comparatively assessed regarding technological, physicochemical, and phytochemical properties. The highest yields were achieved by combining cyclodextrins with whey protein (73.96% for WP+BCD and 75.50% for WP+HPBCD compared to 62.48% of pure extract). The extract-carrier interactions and thermal stability were evaluated by FTIR and DSC analysis, suggesting successful entrapment within the carriers. Carriers reduced the particle diameter (3.99 to 4.86 µm compared to 6.49 µm of pure extract), classifying all encapsulates as microsystems. Carrier blends made the particle size distribution uniform, while SEM analysis revealed the production of more spherical and less aggregated particles. The HPBCD provided the highest encapsulation efficiency, with the highest content of detected aglycones and slightly lower values of their glycosylated forms. An analysis of the dual macromolecule encapsulation systems revealed the highest bioactive preservation potential for SHE+MD+BCD and SHE+WP+HPBCD. Overall, macromolecule combinations of cyclodextrins and conventional biopolymers in the spray-drying process can enhance the functional properties of H. plicatum extract.

Spasmolytic, Antimicrobial, and Antioxidant Activities of Spray-Dried Extracts of Gentiana asclepiadea L. with In Silico Pharmacokinetic Analysis.

This study aimed to evaluate the spasmolytic activity of an underground parts extract of Gentiana asclepiadea L. (Gentianaceae), assess its antioxidant and antimicrobial activities, and explore the impact of extract encapsulation on the aforementioned bioactivities. An extract encapsulated by spray drying with whey protein, pure extract, and pure whey protein were comparatively tested. The main compounds identified via HPLC-DAD analysis underwent in silico ADME assessment. The spasmolytic effect was tested on a model of spontaneous rat ileum contractions, and the mechanism of action was further evaluated on acetylcholine-, KCl-, CaCl2-, BaCl2-, histamine-, N(ω)-nitro-L-arginine methyl ester-, and glibenclamide-modified contractions. The most abundant compounds were secoiridoids (dominantly gentiopicroside), followed by C-glycosylated flavonoids and xanthones. Both pure and encapsulated extracts achieved significant spasmolytic effects, despite the spasmogenic activity of pure whey protein. The extract may exert its spasmolytic effect through multiple pathways, predominantly by antagonizing the Ca2+ channel and opening the K+ channel, while the nitric oxide pathway appears not to be involved. The antimicrobial and antioxidant activities of the pure extract were moderate. The extract stabilized by encapsulation retained all of the tested bioactivities of the unencapsulated extract. The obtained results suggest that G. asclepiadea has potential for use in the treatment of some gastrointestinal complaints and that the encapsulated extract could be a valuable functional ingredient in pharmaceutical and food products.

Spasmolytic Activity of Gentiana lutea L. Root Extracts on the Rat Ileum: Underlying Mechanisms of Action.

The roots of Gentiana lutea L. are utilized in the preparation of various beverages and herbal remedies, serving as a traditional remedy for gastrointestinal ailments. The spasmolytic activity that could substantiate the traditional use of G. lutea root had not been investigated. The main objective goal of the study was to determine the validity of its use as a traditional remedy. The extraction of G. lutea root was performed using a 50% hydroethanolic solvent with three different extraction techniques: ultrasound-assisted extraction (UAE), heat-assisted extraction, and percolation. The spasmolytic activity was tested on isolated rat ileum. The mechanism of action was monitored using the models of spontaneous contractions and acetylcholine-, histamine-, CaCl2-, Bay K8644-, L-NAME-, ODQ-, apamin-, BaCl2-, charybdotoxin-, glibenclamide-, TRAM-34-, and quinine-modified contractions. UAE, having the best bioactivity, was further subjected to a liquid-liquid extraction fractionation. HPLC phytochemical analysis was performed for all tested extracts and fractions. Gentian root extracts were rich in secoiridoids, xanthones, and flavonoids. The UAE has shown better results on spontaneous contractions in comparison to its fractions, leading to the more detailed testing of its spasmolytic mechanism of activity. The extract's activity is primarily mediated through intermediate conductance Ca2+-activated K+ channels, ATP-sensitive K+ channels, voltage-sensitive K+ channels, and mechanisms that activate Ca2+ channels. Overall, the G. lutea root shows great potential in the treatment of spasmodic gastrointestinal ailments.

Correlation between journal metrics-based academic evaluation and researchers' ethics.

The "publish or perish" approach has become an integral part of an academic's life when seeking positions, striving for promotions, or competing for funding. This approach often hinges on journal-based metrics which push researchers to seek publication in journals indexed in the Web of Science. Due to the pressure to publish a certain number of publications in journals indexed in the Web of Science, researchers might attempt to find a journal with a lower impact factor, i.e., less popular and visible journals in the scientific community. Even more concerning is the fact that researchers might publish their results in predatory journals. This paper analyzes the consequence of introducing a journal indicators-based academic evaluation by analyzing productivity and publication patterns of researchers. Moreover, this paper investigates the correlation between journal-based academic evaluation rules and researchers' ethics. The analysis is based on bibliometric data collected from the Web of Science database. The case study subject is the Serbian research landscape before and after the introduction of a journal metrics-based academic evaluation.

An In Vitro and In Silico Characterization of Salvia sclarea L. Methanolic Extracts as Spasmolytic Agents.

The use of medicinal plant species and their products is widespread in the field of gastrointestinal and respiratory diseases. This study aimed to evaluate the traditional use of Salvia sclarea L., clary sage, finding the possible mechanisms of its spasmolytic and bronchodilator actions in in vitro conditions supported by molecular docking analysis, along with the antimicrobial effects. Four dry extracts were prepared from the aerial parts of S. sclarea, using absolute or 80% (v/v) methanol by the method of a single-stage maceration or an ultrasound-assisted extraction. Characterization of the bioactive compounds by high-performance liquid chromatography indicated the presence of significant amounts of polyphenolics, with rosmarinic acid as the prevalent one. The spontaneous ileal contractions were best inhibited by the extract prepared with 80% methanol and maceration. The same extract was superior in the carbachol- and KCl-induced tracheal smooth muscle contractions, being the strongest bronchodilator agent. The most powerful relaxation of KCl-induced ileal contractions was achieved with the extract made of absolute methanol by maceration, while the 80% methanolic extract made with the ultrasound method generated the best spasmolytic effects in the acetylcholine-induced ileal contractions. Docking analysis suggested that apigenin-7-O-glucoside and luteolin-7-O-glucoside exhibited the highest binding affinity to voltage-gated calcium channels. Gram (+) bacteria were more susceptible to the effects of the extracts, particularly Staphylococcus aureus, in contrast to Gram (-) bacteria and Candida albicans. This is the first study to point out the influence of S. sclarea methanolic extracts on the gastrointestinal and respiratory spasm reduction, paving the way for their potential place in complementary medicine.

Economic Justification Analysis of Minimally Invasive versus Conventional Aortic Valve Replacement.

There is no definitive consensus about the cost-effectiveness of minimally invasive aortic valve replacement (AVR) (MI-AVR) compared to conventional AVR (C-AVR). The aim of this study was to compare the rate of postoperative complications and total hospital costs of MI-AVR versus C-AVR overall and by the type of aortic prosthesis (biological or mechanical). Our single-center retrospective study included 324 patients over 18 years old who underwent elective isolated primary AVR with standard stented AV prosthesis at the Institute for Cardiovascular Diseases "Dedinje" between January 2019 and December 2019. Reintervention, emergencies, combined surgical interventions, and patients with sutureless valves were excluded. In both MI-AVR and C-AVR, mechanical valve implantation contributed to overall reduction of hospital costs with equal efficacy. The cost-effectiveness ratio indicated that C-AVR is cheaper and yielded a better clinical outcome with mechanical valve implantation (67.17 vs. 69.5). In biological valve implantation, MI-AVR was superior. MI-AVR patients had statistically significantly higher LVEF and a lower Euro SCORE than C-AVR patients (Mann-Whitney U-test, p = 0.002 and p = 0.002, respectively). There is a slight advantage to MI-AVR vs. C-AVR, since it costs EUR 9.44 more to address complications that may arise. Complications (mortality, early reoperation, cerebrovascular insult, pacemaker implantation, atrial fibrillation, AV block, systemic inflammatory response syndrome, wound infection) were less frequent in the MI-AVR, making MI-AVR more economically justified than C-AVR (18% vs. 22.1%).

Natural deep eutectic solvents combined with cyclodextrins: A novel strategy for chokeberry anthocyanins extraction.

Innovative eco-friendly methods based on natural deep eutectic solvents (NaDES) coupled with ultrasound-assisted extraction were employed for chokeberry anthocyanins extractions. Nine different NaDES composed of choline chloride as a hydrogen bond acceptor and organic acids (lactic, citric, malic), sugars (glucose, fructose), polyols (glycerol, 1,2-propanediol, sorbitol), and an amide (urea) as hydrogen bond donors were screened. Malic acid-containing NaDES was selected for optimization extraction conditions (time, temperature, water in NaDES) by response surface methodology. Optimal conditions for simultaneously maximizing the anthocyanins extraction (cyanidin-3-O-glucoside, cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, total anthocyanins) were 42.7 °C, 90 min, and 40 % (w/w) water in NaDES. In the next stage of this study, the possibility to improve anthocyanins extraction at elevated temperatures by incorporating different concentrations of hydroxypropyl-ß-cyclodextrin into selected NaDES was investigated. The extraction was improved at hydroxypropyl-ß-cyclodextrin concentrations up to 3 % (w/w). To clarify the interaction of NaDES components and anthocyanins, a molecular dynamic simulation was conducted.

Ultrasound-Assisted Water Extraction of Gentiopicroside, Isogentisin, and Polyphenols from Willow Gentian "Dust" Supported by Hydroxypropyl-ß-Cyclodextrin as Cage Molecules.

The residue after sieving ("dust") from the willow gentian underground parts is an unexploited herbal tea by-product, although it contains valuable bioactive compounds. Cyclodextrins as efficient green co-solvents, cage molecules, and multifunctional excipients could improve the extraction and contribute to the added value of the resulting extracts. The objective of this study was to determine the optimal conditions for the extraction of gentiopicroside, isogentisin, and total phenolics (TPC) from willow gentian "dust" using ultrasound-assisted water extraction coupled with hydroxypropyl-ß-cyclodextrin (HPßCD). The influence of extraction temperature (X1: 20-80 °C), time (X2: 20-50 min), and HPßCD concentration (X3: 2-4% w/v) was analyzed employing the response surface methodology (RSM). The optimal extraction conditions for simultaneously maximizing the extraction yield of all monitored responses were X1: 74.89 °C, X2: 32.57 min, and X3: 3.01% w/v. The experimentally obtained response values under these conditions (46.96 mg/g DW for gentiopicroside, 0.51 mg/g DW for isogentisin, and 12.99 mg GAE/g DW for TPC) were in close agreement with those predicted, thus confirming the suitability and good predictive accuracy of the developed RSM models. Overall, the developed extraction system could be an applicable alternative strategy to improve the extraction of bioactive compounds from the underutilized "dust" of willow gentian underground parts.

Bioassay-Guided Skin-Beneficial Effects of Fractionated Sideritis raeseri subsp. raeseri Extract.

This study aimed to evaluate the potentials for skin-beneficial effects of the hydroethanolic extract of the aerial parts of ironwort (Sideritis raeseri Boiss. & Heldr. subsp. raeseri) and its fractions (petroleum ether, ethyl acetate, n-butanol and water). For these purposes, chemical analysis and in vitro antioxidant, anti-tyrosinase and antimicrobial assays, as well as determination of sun protection factor (SPF), were performed. The highest total phenolic content and quantity of individual flavonoids, chlorogenic acid and verbascoside were determined in the n-butanol fraction, which is in line with results obtained for antioxidant activity. The greatest antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, the most common causative agents of the skin infections in humans, was exhibited by the ethyl acetate fraction. The strongest anti-tyrosinase activity was shown by the hydroethanolic extract (52.64% of inhibition at 100 µg/mL). Almost all tested samples showed photoprotective activity with SPF higher than 6 obtained at a low concentration of 0.1 mg/mL, which was more than 15 for the butanol fraction. These findings revealed that the hydroethanolic extract of S. raeseri aerial parts could be a valuable ingredient in the formulation of cosmetic and medicinal products intended to overcome various skin disorders.

Ultrasound-Assisted Natural Deep Eutectic Solvents Extraction of Bilberry Anthocyanins: Optimization, Bioactivities, and Storage Stability.

Bilberry fruits (Vaccinium myrtillus L.) are one of the richest natural sources of anthocyanins and are widely used due to their pharmacological and nutritional properties. To ensure their maximum application potential, it is necessary to overcome the limitations of conventional extraction solvents and techniques. This study aimed to develop a green method for bilberry anthocyanin extraction using natural deep eutectic solvents (NaDES) integrated with ultrasound-assisted extraction (UAE) in order to define extraction conditions that will prevent decomposition of the anthocyanins or the loss of bioactivity. After a screening of ten different NaDES, choline chloride:sorbitol (1:1) was selected as the most effective. Furthermore, the influence analysis and optimization of the NaDES-UAE extraction conditions were carried out employing response surface methodology. The optimal conditions were found to be an extraction time of 37.63 min, a temperature of 48.38 °C, and 34.79% (w/w) water in NaDES. The extraction yields of target compounds under optimized extraction conditions were 0.27 mg/g DW of cyanidin-3-O-glucoside and 2.12 mg CGE/g DW of TAC. The obtained optimized extract showed promising radical scavenging and antimicrobial activity. A stability study with the optimized extract revealed that refrigerated storage at 4 °C in the dark provided the best anthocyanins preservation. Overall, the developed NaDES-UAE method showed promising application potential and can be considered as a high-efficiency green alternative to conventional anthocyanins extraction methods, enabling the preservation of active ingredients and the bioactivity of extracts.