bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion of Oleic Acid into Azelaic and Pelargonic Acid by a Chemo-Enzymatic Route
Authors: Brenna Elisabetta , Colombo Danilo , Di Lecce Giuseppe , Gatti Francesco G. , Ghezzi Maria Chiara , Tentori Francesca , Tessaro Davide , Viola Mariacristina
Published: April 2020

A chemo-enzymatic approach for the conversion of oleic acid into azelaic and pelargonic acid is herein described. It represents a sustainable alternative to ozonolysis, currently employed at the industrial scale to perform the reaction. Azelaic acid is produced in high chemical purity in 44% isolation yield after three steps, avoiding column chromatography purifications. In the first step, the lipase-mediated generation of peroleic acid in the presence of 35% H2O2 is employed for the self-epoxidation of the unsaturated acid to the corresponding oxirane derivative. This intermediate is submitted to in situ acid-catalyzed opening, to afford 9,10-dihydroxystearic acid, which readily crystallizes from the reaction medium. The chemical oxidation of the diol derivative, using atmospheric oxygen as a stoichiometric oxidant with catalytic quantities of Fe(NO3)3∙9∙H2O, (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), and NaCl, affords 9,10-dioxostearic acid which is cleaved by the action of 35% H2O2 in mild conditions, without requiring any catalyst, to give pelargonic and azelaic acid.
Inhalation Administration of the Bicyclic Ethers 1,8- and 1,4-cineole Prevent Anxiety and Depressive-Like Behaviours in Mice
Authors: Dougnon Godfried , Ito Michiho
Published: April 2020

The anxiolytic and antidepressant-like activities of the naturally occurring monoterpene 1,8-cineole and its structural isomer 1,4-cineole were evaluated in mice via inhalation administration at doses ranging from 4 × 10−6 to 4 × 10−1 mg per 400 μL of triethyl citrate. Mice were tested for anxiety-like behaviours by using the light–dark box test (LDB) and marble-burying test (MBT) and for depression-like symptoms by using the forced swimming test (FST) and tail suspension test (TST). Diazepam and fluoxetine were used as standard drugs for anxiolytic and antidepressant tests, respectively. The results showed that 1,8-cineole at 4 × 10−4 mg, and 1,4-cineole at 4 × 10−4 and 4 × 10−3 mg significantly increased the amount of time spent in the light box and the number of entries in the light box in the LDB as well as reduced the number of marbles buried in the MBT relative to those in the control, suggesting an anxiolytic effect. Similarly, 1,8-cineole at 4 × 10−4 and 4 × 10−2 mg and 1,4-cineole at doses of 4 × 10−4 to 4 × 10−2 mg significantly reduced immobility times in the FST and TST relative to those of the control, suggesting an antidepressant activity. The role of the GABAA/benzodiazepine receptor system in the anxiolytic effects of 1,8- and 1,4-cineole was investigated through co-administration of flumazenil, a GABAergic system antagonist. Flumazenil reversed the effects of diazepam and 1,8-cineole, suggesting that 1,8-cineole affects the GABAA/benzodiazepine receptors. Collectively, the results suggest that inhaled 1,8- and 1,4-cineole prevented anxiety and depressive-like symptoms in classic mice models.
In Vitro Anti-Leishmanial Effect of Metallic Meso-Substituted Porphyrin Derivatives against Leishmania braziliensis and Leishmania panamensis Promastigotes Properties
Authors: Espitia-Almeida Fabian , Díaz-Uribe Carlos , Vallejo William , Gómez-Camargo Doris , Romero Bohórquez Arnold R.
Published: April 2020

In this study, a family of porphyrins based on 5,10,15,20-Tetrakis(4-ethylphenyl)porphyrin (1, Ph) and six metallo-derivatives (Zn2+(2, Ph-Zn), Sn4+(3, Ph-Sn), Mn2+ (4, Ph-Mn), Ni2+ (5, Ph-Ni), Al3+ (6, Ph-Al), and V3+ (7, Ph-V)) were tested as photosensitizers for photodynamic therapy against Leishmania braziliensis and panamensis. The singlet oxygen quantum yield value (ΦΔ) for (1–7) was measured using 1,3-diphenylisobenzofuran (DPBF) as a singlet oxygen trapping agent and 5,10,15,20-(tetraphenyl)-porphyrin (H2TPP) as a reference standard; besides, parasite viability was estimated by the MTT assay. After metal insertion into the porphyrin core, the ΦΔ increased from 0.76–0.90 and cell viability changed considerably. The ΦΔ and metal type changed the cytotoxic activity. Finally, (2) showed both the highest ΦΔ (0.90) and the best photodynamic activity against the parasites studied (IC50 of 1.2 μM).
Characterization of Rosa canina Fruits Collected in Urban Areas of Slovakia. Genome Size, iPBS Profiles and Antioxidant and Antimicrobial Activities
Authors: Rovná Katarína , Ivanišová Eva , Žiarovská Jana , Ferus Peter , Terentjeva Margarita , Kowalczewski Przemysław Łukasz , Kačániová Miroslava
Published: April 2020

The studies of plant bacterial endophytes, colonizing the plant tissues without any signs of diseases, are essential for understanding of ecological interactions. The aim of our study is to detect microbiological contamination and to assess the antimicrobial, antioxidant activity, total phenolic, carotenoid content, genome size, and ploidy of non-cultivated Rosa canina sampled from urban areas. Samples of Rosa canina fruits were collected in three locations in Slovakia. The highest total viable count and the Enterobacteriaceae count in fruits were 4.32 log CFU/g and 4.29 log CFU/g, respectively. Counts of the mesophilic anaerobic sporulating bacteria, Pseudomonas spp., and of the microscopic fungi and yeasts were 3.00, 2.15 log CFU/g, 3.65 log CFU/g, and 2.76 log CFU/g, respectively. Regarding the antimicrobial activity, Escherichia coli and Klebsiela oxytoca were the most sensitive species among the assayed microorganisms to the treatment with the ethanolic extracts of Rosa canina fruits. The fruits were rich in bioactive compounds, polyphenols, and carotenoids, that could be related to their antioxidant activity. Genome sizes of analyzed samples ranged from 2.3 to 2.96. DNA-based fingerprinting obtained by iPBS markers of the Rosa canina var. lapidicola Heinr. Braun., was characterized by some distinctive inserted loci. An interdisciplinary study was performed for the dog roses from different parts of Slovakia that resulted in deeper characterization of this species.
Chemical Composition and Biological Activities of Essential Oils from Peels of Three Citrus Species
Authors: Caputo Lucia , Cornara Laura , Bazzicalupo Miriam , De Francesco Clara , De Feo Vincenzo , Trombetta Domenico , Smeriglio Antonella
Published: April 2020

Background: Fruit peels are generally underutilized byproducts of the food industry, although they are valuable sources of bioactive compounds. The aim of this study is to evaluate a new application for three Citrus peel EOs as bio-herbicides. Methods: After a micro-morphological evaluation of Citrus peels by SEM analysis, the phytochemical composition of the EOs of Citrus × bergamia Risso & Poit., Citrus × myrtifolia Raf., and Citrus limon (L.) Osbeck was characterized by GC/FID and GC/MS analyses. The in vitro phytotoxicity against germination and initial radical elongation of several crop and weed species was evaluated. Furthermore, the eco-compatibility of these EOs has been assessed by the brine shrimp (Artemia salina) lethality assay. Results: SEM analysis highlighted the morphometric differences of the schizolysigenous pockets among the peels of the three Citrus species. Oxygenated monoterpenes are the main constituents in C. × bergamia (51.09%), whereas monoterpene hydrocarbons represent the most abundant compounds in C. × myrtifolia (82.15%) and C. limon (80.33%) EOs. They showed marked and selective phytotoxic activity in vitro, often at very low concentration (0.1 μg/mL) against all plant species investigated, without showing any toxicity on Artemia salina, opening the perspective of their use as safe bio-herbicides.
Bioassay-Guided Isolation of Antiproliferative Compounds from Limbarda crithmoides (L.) Dumort
Authors: Adorisio Sabrina , Giamperi Laura , Bucchini Anahi Elena Ada , Delfino Domenico Vittorio , Marcotullio Maria Carla
Published: April 2020

Limbarda crithmoides (L.) Dumort (Asteraceae) n-hexane extract displayed high cell proliferation inhibitory activity against acute myeloid leukaemia cells (OCI-AML3) and was therefore subjected to a bioassay-guided multistep separation procedure. Two thymol derivatives, namely 10-acetoxy-8,9-epoxythymol tiglate (1) and 10-acetoxy-9-chloro-8,9-dehydrothymol (2), were isolated and identified by means of NMR spectroscopy. Both of them exhibited a significant dose-dependent inhibition of cell proliferation.
The Anti-Inflammatory and Antimicrobial Potential of Selected Ethnomedicinal Plants from Sri Lanka
Authors: Napagoda Mayuri , Gerstmeier Jana , Butschek Hannah , De Soyza Sudhara , Pace Simona , Lorenz Sybille , Qader Mallique , Witharana Sanjeeva , Nagahawatte Ajith , Wijayaratne Gaya , Svatoš Aleš , Jayasinghe Lalith , Koeberle Andreas , Werz Oliver
Published: April 2020

Traditional folk medicine in Sri Lanka is mostly based on plants and plant-derived products, however, many of these medicinal plant species are scientifically unexplored. Here, we evaluated the anti-inflammatory and antimicrobial potency of 28 different extracts prepared from seven popular medicinal plant species employed in Sri Lanka. The extracts were subjected to cell-based and cell-free assays of 5-lipoxygenase (5-LO), microsomal prostaglandin E2 synthase (mPGES)-1, and nitric oxide (NO) scavenging activity. Moreover, antibacterial and disinfectant activities were assessed. Characterization of secondary metabolites was achieved by gas chromatography coupled to mass spectrometric (GC-MS) analysis. n-Hexane- and dichloromethane-based extracts of Garcinia cambogia efficiently suppressed 5-LO activity in human neutrophils (IC50 = 0.92 and 1.39 µg/mL), and potently inhibited isolated human 5-LO (IC50 = 0.15 and 0.16 µg/mL) and mPGES-1 (IC50 = 0.29 and 0.49 µg/mL). Lipophilic extracts of Pothos scandens displayed potent inhibition of mPGES-1 only. A methanolic extract of Ophiorrhiza mungos caused significant NO scavenging activity. The lipophilic extracts of G. cambogia exhibited prominent antibacterial and disinfectant activities, and GC-MS analysis revealed the presence of fatty acids, sesquiterpenes and other types of secondary metabolites. Together, our results suggest the prospective utilization of G. cambogia as disinfective agent with potent anti-inflammatory properties.
PF74 and Its Novel Derivatives Stabilize Hexameric Lattice of HIV-1 Mature-Like Particles
Authors: Dostálková Alžběta , Škach Kryštof , Kaufman Filip , Křížová Ivana , Hadravová Romana , Flegel Martin , Ruml Tomáš , Hrabal Richard , Rumlová Michaela
Published: April 2020

A major structural retroviral protein, capsid protein (CA), is able to oligomerize into two different hexameric lattices, which makes this protein a key component for both the early and late stages of HIV-1 replication. During the late stage, the CA protein, as part of the Gag polyprotein precursor, facilitates protein–protein interactions that lead to the assembly of immature particles. Following protease activation and Gag polyprotein processing, CA also drives the assembly of the mature viral core. In the early stage of infection, the role of the CA protein is distinct. It controls the disassembly of the mature CA hexameric lattice i.e., uncoating, which is critical for the reverse transcription of the single-stranded RNA genome into double stranded DNA. These properties make CA a very attractive target for small molecule functioning as inhibitors of HIV-1 particle assembly and/or disassembly. Of these, inhibitors containing the PF74 scaffold have been extensively studied. In this study, we reported a series of modifications of the PF74 molecule and its characterization through a combination of biochemical and structural approaches. Our data supported the hypothesis that PF74 stabilizes the mature HIV-1 CA hexameric lattice. We identified derivatives with a higher in vitro stabilization activity in comparison to the original PF74 molecule.
Radiative Colloidal Investigation for Thermal Transport by Incorporating the Impacts of Nanomaterial and Molecular Diameters (dNanoparticles, dFluid): Applications in Multiple Engineering Systems
Authors: Ahmed Naveed , Adnan  , Khan Umar , Mohyud-Din Syed Tauseef , Chu Yu-Ming , Khan Ilyas , Nisar Kottakkaran Sooppy
Published: April 2020

Thermal enhancement and irreversible phenomena in colloidal suspension (Al2O3-H2O) is a potential topic of interest from the aspects of industrial, mechanical and thermal engineering; heat exchangers; coolant car radiators; and bio-medical, chemical and civil engineering. In the light of these applications, a colloidal analysis of Al2O3-H2O was made. Therefore, a colloidal model is considered and treated numerically. The significant influences of multiple parameters on thermal enhancement, entropy generation and Bejan parameter are examined. From the presented colloidal model, it is explored that Al2O3-H2O is better for the applications of mechanical and applied thermal engineering. Moreover, fraction factor tiny particles are significant parameters which enhanced the thermal capability of the Al2O3-H2O suspension.
Nanostructured ZnO/Ag Film Prepared by Magnetron Sputtering Method for Fast Response of Ammonia Gas Detection
Authors: Zheng Yiran , Li Min , Wen Xiaoyan , Ho Ho-Pui , Lu Haifei
Published: April 2020

Possessing a large surface-to-volume ratio is significant to the sensitive gas detection of semiconductor nanostructures. Here, we propose a fast-response ammonia gas sensor based on porous nanostructured zinc oxide (ZnO) film, which is fabricated through physical vapor deposition and subsequent thermal annealing. In general, an extremely thin silver (Ag) layer (1, 3, 5 nm) and a 100 nm ZnO film are sequentially deposited on the SiO2/Si substrate by a magnetron sputtering method. The porous nanostructure of ZnO film is formed after thermal annealing contributed by the diffusion of Ag among ZnO crystal grains and the expansion of the ZnO film. Different thicknesses of the Ag layer help the formation of different sizes and quantities of hollows uniformly distributed in the ZnO film, which is demonstrated to hold superior gas sensing abilities than the compact ZnO film. The responses of the different porous ZnO films were also investigated in the ammonia concentration range of 10 to 300 ppm. Experimental results demonstrate that the ZnO/Ag(3 nm) sensor possesses a good electrical resistance variation of 85.74% after exposing the sample to 300 ppm ammonia gas for 310 s. Interestingly, a fast response of 61.18% in 60 s for 300 ppm ammonia gas has been achieved from the ZnO/Ag(5 nm) sensor, which costs only 6 s for the response increase to 10%. Therefore, this controllable, porous, nanostructured ZnO film maintaining a sensitive gas response, fabricated by the physical deposition approach, will be of great interest to the gas-sensing community.
Computational and Spectroscopic Studies of Carbon Disulfide
Authors: Adilina Indri B. , Aulia Fauzan , Fitriady Muhammad A. , Oemry Ferensa , Widjaya Robert R. , Parker Stewart F.
Published: April 2020

The vibrational spectroscopy of CS2 has been investigated many times in all three phases. However, there is still some ambiguity about the location of two of the modes in the solid state. The aim of this work was to locate all of the modes by inelastic neutron scattering (INS) spectroscopy, (which has no selection rules), and to use periodic density functional theory to provide a complete and unambiguous assignment of all the modes in the solid state. A comparison of the observed and calculated INS spectra shows generally good agreement. All four of the ν2 bending mode components are calculated to fall within 14 cm−1. Inspection of the spectrum shows that there are no bands close to the intense feature at 390 cm−1 (assigned to ν2); this very strongly indicates that the Au mode is within the envelope of the 390 cm−1 band. Based on a simulation of the band shape of the 390 cm−1 feature, the most likely position of the optically forbidden component of the ν2 bending mode is 393 ± 2 cm−1. The calculations show that the optically inactive Au translational mode is strongly dispersed, so it does not result in a single feature in the INS spectrum.
Tuning up Transcription Factors for Therapy
Authors: Becskei Attila
Published: April 2020

The recent developments in the delivery and design of transcription factors put their therapeutic applications within reach, exemplified by cell replacement, cancer differentiation and T-cell based cancer therapies. The success of such applications depends on the efficacy and precision in the action of transcription factors. The biophysical and genetic characterization of the paradigmatic prokaryotic repressors, LacI and TetR and the designer transcription factors, transcription activator-like effector (TALE) and CRISPR-dCas9 revealed common principles behind their efficacy, which can aid the optimization of transcriptional activators and repressors. Further studies will be required to analyze the linkage between dissociation constants and enzymatic activity, the role of phase separation and squelching in activation and repression and the long-range interaction of transcription factors with epigenetic regulators in the context of the chromosomes. Understanding these mechanisms will help to tailor natural and synthetic transcription factors to the needs of specific applications.
Synthesizing of Novel Bulk (Zr67Cu33)100−xWx(x; 5–30 at%) Glassy Alloys by Spark Plasma Sintering of Mechanically Alloyed Powders
Authors: El-Eskandarany M. Sherif , Ali Naser
Published: April 2020

Metallic glassy alloys with their short-range order have received considerable attention since their discovery in 1960’s. The worldwide interest in metallic glassy alloys is attributed to their unique mechanical, physical, and chemical properties, which cannot be found together in long-range order alloys of the same compositions. Traditional preparation methods of metallic glasses, such as rapid solidification of melts, always restrict the formation of glassy alloys with large atomic fraction (above 3–5 at%) of high melting point metals (Ta, Mo, W). In this study, (Zr67Cu33)100−xWx(x; 5–30 at%) metallic glassy alloys were fabricated through a mechanical alloying approach, which starts from the elemental powders. This system shows excellent glass forming ability in a wide range of W (0 ≤ x ≥ 30 at%). We have proposed a spark plasma sintering technique to prepare nearly full-dense large sized (20 × 20 mm) bulk metallic glassy alloys. The as-consolidated bulk metallic glassy alloys were seen to possess high thermal stability when compared with the other metallic glassy systems. This is implied by their high glass transition temperature (722–735 K), wide range of supercooled liquid region (39 K to over 100 K), and high values of crystallization temperature (761 K to 823 K). In addition, the fabricated ternary systems have revealed high microhardness values.
Cannabis sativa L. Inflorescences from Monoecious Cultivars Grown in Central Italy: An Untargeted Chemical Characterization from Early Flowering to Ripening
Authors: Ingallina Cinzia , Sobolev Anatoly P. , Circi Simone , Spano Mattia , Fraschetti Caterina , Filippi Antonello , Di Sotto Antonella , Di Giacomo Silvia , Mazzoccanti Giulia , Gasparrini Francesco , Quaglio Deborah , Campiglia Enio , Carradori Simone , Locatelli Marcello , Vinci Giuliana , Rapa Mattia , Ciano Salvatore , Giusti Anna Maria , Botta Bruno , Ghirga Francesca , Capitani Donatella , Mannina Luisa
Published: April 2020

The chemical composition of the inflorescences from four Cannabis sativa L. monoecious cultivars (Ferimon, Uso-31, Felina 32 and Fedora 17), recently introduced in the Lazio Region, was monitored over the season from June to September giving indications on their sensorial, pharmaceutical/nutraceutical proprieties. Both untargeted (NMR) and targeted (GC/MS, UHPLC, HPLC-PDA/FD and spectrophotometry) analyses were carried out to identify and quantify compounds of different classes (sugars, organic acids, amino acids, cannabinoids, terpenoids, phenols, tannins, flavonoids and biogenic amines). All cultivars in each harvesting period showed a THC content below the Italian legal limit, although in general THC content increased over the season. Citric acid, malic acid and glucose showed the highest content in the late flowering period, whereas the content of proline drastically decreased after June in all cultivars. Neophytadiene, nerolidol and chlorogenic acid were quantified only in Felina 32 cultivar, characterized also by a very high content of flavonoids, whereas alloaromadendrene and trans-cinnamic acid were detected only in Uso-31 cultivar. Naringenin and naringin were present only in Fedora 17 and Ferimon cultivars, respectively. Moreover, Ferimon had the highest concentration of biogenic amines, especially in July and August. Cadaverine was present in all cultivars but only in September. These results suggest that the chemical composition of Cannabis sativa L. inflorescences depends on the cultivar and on the harvesting period. Producers can use this information as a guide to obtain inflorescences with peculiar chemical characteristics according to the specific use.
A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications
Authors: Kerru Nagaraju , Gummidi Lalitha , Maddila Suresh , Gangu Kranthi Kumar , Jonnalagadda Sreekantha B.
Published: April 2020

The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.
Formation of Phases in Reactively Sintered TiAl3 Alloy
Authors: Školáková Andrea , Salvetr Pavel , Leitner Jindřich , Lovaši Tomáš , Novák Pavel
Published: April 2020

This work highlights new results on the synthesis of the TiAl3 intermetallic phase using self-propagating high-temperature synthesis. This method is considered a promising sintering route for intermetallic compounds. It was found that the reactions proceed in two stages. Below the melting point of aluminum, the Ti2Al5 phase forms at 450 °C after long annealing times by a direct solid-state reaction between the aluminum and titanium, and is converted consequently to TiAl3. This is a completely new finding; until now, many authors have believed in the preferential formation of the TiAl3 phase. The second stage, the self-propagating strongly exothermic reaction, proceeds above the melting point of aluminum. It leads to the formation of the TiAl3 phase accompanied by Ti2Al5 and Ti3Al phases. The reaction mechanism was shown in the form of chemical equations, which were supported by calculating Gibbs energy. Reaction temperatures (Tonset, Tmaximum, and Toffset) were determined after induction heating thanks to recording by an optical pyrometer. This finding provides completely new opportunities for the determination of activation energy at heating rates, in which common calorimeters are not able to detect a response or even measure. Now, the whole procedure will become accessible.
Stealth Coating of Nanoparticles in Drug-Delivery Systems
Authors: Fam See Yee , Chee Chin Fei , Yong Chean Yeah , Ho Kok Lian , Mariatulqabtiah Abdul Razak , Tan Wen Siang
Published: April 2020

Nanoparticles (NPs) have emerged as a powerful drug-delivery tool for cancer therapies to enhance the specificity of drug actions, while reducing the systemic side effects. Nonetheless, NPs interact massively with the surrounding physiological environments including plasma proteins upon administration into the bloodstream. Consequently, they are rapidly cleared from the blood circulation by the mononuclear phagocyte system (MPS) or complement system, resulting in a premature elimination that will cause the drug release at off-target sites. By grafting a stealth coating layer onto the surface of NPs, the blood circulation half-life of nanomaterials can be improved by escaping the recognition and clearance of the immune system. This review focuses on the basic concept underlying the stealth behavior of NPs by polymer coating, whereby the fundamental surface coating characteristics such as molecular weight, surface chain density as well as conformations of polymer chains are of utmost importance for efficient protection of NPs. In addition, the most commonly used stealth polymers such as poly(ethylene glycol) (PEG), poly(2-oxazoline) (POx), and poly(zwitterions) in developing long-circulating NPs for drug delivery are also thoroughly discussed. The biomimetic strategies, including the cell-membrane camouflaging technique and CD47 functionalization for the development of stealth nano-delivery systems, are highlighted in this review as well.
Application of Continuous Glucose Monitoring for Assessment of Individual Carbohydrate Requirement during Ultramarathon Race
Authors: Ishihara Kengo , Uchiyama Natsuki , Kizaki Shino , Mori Emi , Nonaka Tsutomu , Oneda Hiroshi
Published: April 2020

Background: The current study intended to evaluate the feasibility of the application of continuous glucose monitoring to guarantee optimal intake of carbohydrate to maintain blood glucose levels during a 160-km ultramarathon race. Methods: Seven ultramarathon runners (four male and three female) took part in the study. The glucose profile was monitored continuously throughout the race, which was divided into 11 segments by timing gates. Running speed in each segment was standardized to the average of the top five finishers for each gender. Food and drink intake during the race were recorded and carbohydrate and energy intake were calculated. Results: Observed glucose levels ranged between 61.9–252.0 mg/dL. Average glucose concentration differed from the start to the end of the race (104 ± 15.0 to 164 ± 30.5 SD mg/dL). The total amount of carbohydrate intake during the race ranged from 0.27 to 1.14 g/kg/h. Glucose concentration positively correlated with running speeds in segments (P < 0.005). Energy and carbohydrate intake positively correlated with overall running speed (P < 0.01). Conclusion: The present study demonstrates that continuous glucose monitoring could be practical to guarantee optimal carbohydrate intake for each ultramarathon runner.
Four Weeks of Time-Restricted Feeding Combined with Resistance Training Does Not Differentially Influence Measures of Body Composition, Muscle Performance, Resting Energy Expenditure, and Blood Biomarkers
Authors: Stratton Matthew T. , Tinsley Grant M. , Alesi Michaela G. , Hester Garrett M. , Olmos Alex A. , Serafini Paul R. , Modjeski Andrew S. , Mangine Gerald T. , King Kelsey , Savage Shelby N. , Webb Austin T. , VanDusseldorp Trisha A.
Published: April 2020

Recently, interest in time-restricted feeding (TRF) has increased from reports highlighting improvements in body composition and muscular performance measures. Twenty-six recreationally active males were randomly assigned to either TRF (n = 13; ~22.9 years; 82.0 kg; 178.1 cm; 8 h eating window, 25% caloric deficit, 1.8 g/kg/day protein) or normal diet (ND; n = 13; ~22.5 years; 83.3 kg; 177.5 cm; normal meal pattern; 25% caloric deficit, 1.8 g/kg/day protein) groups. Participants underwent 4-weeks of supervised full body resistance training. Changes in body composition (fat mass (FM), fat free mass (FFM), and body fat percentage (BF%)), skeletal muscle cross sectional area (CSA) and muscle thickness (MT) of the vastus lateralis (VL), rectus femoris, (RF), and biceps brachii (BB) muscles, resting energy expenditure (REE), muscular performance, blood biomarkers, and psychometric parameters were assessed. Significant (p < 0.05) decreases were noted in BM, FM, BF%, testosterone, adiponectin, and REE, along with significant increases in BP1RM, LP1RM, VJHT, VJPP, VLCSA, BBCSA, and BBMT in both groups. Plasma cortisol levels were significantly elevated at post (p = 0.018) only in ND. Additionally, FFM was maintained equally between groups. Thus, a TRF style of eating does not enhance reductions in FM over caloric restriction alone during a 4-week hypocaloric diet.
Content Validation through Expert Judgement of an Instrument on the Nutritional Knowledge, Beliefs, and Habits of Pregnant Women
Authors: Fernández-Gómez Elisabet , Martín-Salvador Adelina , Luque-Vara Trinidad , Sánchez-Ojeda María Angustias , Navarro-Prado Silvia , Enrique-Mirón Carmen
Published: April 2020

The aim of this study was to conduct content validation through expert judgement of an instrument which explores the nutritional knowledge, beliefs, and habits during pregnancy. This is a psychometric study in which 14 experts participated in the evaluation of each of the questionnaire items, which were divided into two blocks according to the characteristics of sufficiency, clarity, coherence, and relevance. Fleiss’ κ statistic was used to measure strength of agreement. A pre-test with 102 participants was conducted to measure the degree of understandability of the instrument. The strength of agreement obtained for each of the dimensions was almost perfect. For each pair of experts, strength of agreement ranged between substantial and almost perfect. Sufficiency was the characteristic of the questionnaire that obtained the highest values in the two blocks, and was also the most statistically significant (p < 0.001). Coherence was the most statistically significant characteristic in the first block (p = 0.030). Clarity was the most statistically significant characteristic in the second block (p = 0.037). The wording of five of the twenty original items was corrected. The new version of the instrument attained a high degree of understandability. The results suggest that the instrument is valid and may therefore be applied.
Flaxseed (Linum Usitatissimum L.) Supplementation in Patients Undergoing Lipoprotein Apheresis for Severe Hyperlipidemia—A Pilot Study
Authors: Kanikowska Dominika , Korybalska Katarzyna , Mickiewicz Agnieszka , Rutkowski Rafał , Kuchta Agnieszka , Sato Maki , Kreft Ewelina , Fijałkowski Marcin , Gruchała Marcin , Jankowski Maciej , Bręborowicz Andrzej , Witowski Janusz
Published: April 2020

Being rich in polyunsaturated fatty acids, flaxseed (Linum usitatissimum L.) is thought to be able to decrease lipid levels and dampen inflammation. In this pilot study, we aimed to determine whether flaxseed supplementation could improve the profiles of lipids and inflammatory mediators in patients with severe hyperlipidemia resistant to conventional lipid-lowering pharmacotherapy and requiring lipoprotein apheresis. To this end, six patients received, blindly—in addition to their normal lipoprotein apheresis regimen—a 10-week dietary supplementation with flaxseed (28 g/d) administered in biscuits. This was followed by a 10-week washed out-period and a 10-week supplementation phase with whole wheat placebo. Blood samples were collected at the end of each phase, before the lipoprotein apheresis session. The primary endpoint was the lipid profile and the secondary endpoints were the concentrations of inflammatory mediators and tolerability. Flaxseed supplementation was well-tolerated and resulted in a consistent and significant decrease in total cholesterol and low-density lipoprotein (LDL) levels. The median (and range) percentage decrease was 11.5% (0–18.8) and 7.3% (4.4–26.6), for cholesterol (p = 0.015) and LDL-C (p = 0.003), respectively. On the other hand, there was no significant effect of flaxseed on lipoprotein(a) (Lp(a)), C-reactive protein (CRP), and interleukin 6 (IL-6) concentrations. These observations indicate that flaxseed can produce a cholesterol- and LDL-lowering effect in patients treated with lipoprotein apheresis. Thus, flaxseed supplementation may help to control cholesterol in this patient population. The flaxseed supplementation protocol applied may be of use for further adequately-powered studies to validate and extend our findings.
Anserine Reverses Exercise-Induced Oxidative Stress and Preserves Cellular Homeostasis in Healthy Men
Authors: Alkhatib Ahmad , Feng Wen-Hsin , Huang Yi-Jen , Kuo Chia-Hua , Hou Chien-Wen
Published: April 2020

The study tested whether anserine (beta-alanyl-3-methyl-l-histidine), the active ingredient of chicken essence affects exercise-induced oxidative stress, cell integrity, and haematology biomarkers. In a randomized placebo-controlled repeated-measures design, ten healthy men ingested anserine in either a low dose (ANS-LD) 15 mg·kg−1·bw−1, high dose (ANS-HD) 30 mg·kg−1·bw−1, or placebo (PLA), following an exercise challenge (time to exhaustion), on three separate occasions. Anserine supplementation increased superoxide dismutase (SOD) by 50% (p < 0.001, effect size d = 0.8 for both ANS-LD and ANS-HD), and preserved catalase (CAT) activity suggesting an improved antioxidant activity. However, both ANS-LD and ANS-HD elevated glutathione disulfide (GSSG), (both p < 0.001, main treatment effect), and consequently lowered the glutathione to glutathione disulfide (GSH/GSSG) ratio compared with PLA (p < 0.01, main treatment effect), without significant effects on thiobarbituric acid active reactive substances (TBARS). Exercise-induced cell damage biomarkers of glutamic-oxaloacetic transaminase (GOT) and myoglobin were unaffected by anserine. There were slight but significant elevations in glutamate pyruvate transaminase (GPT) and creatine kinase isoenzyme (CKMB), especially in ANS-HD (p < 0.05) compared with ANS-LD or PLA. Haematological biomarkers were largely unaffected by anserine, its dose, and without interaction with post exercise time-course. However, compared with ANS-LD and PLA, ANS-HD increased the mean cell volume (MCV), and decreased the mean corpuscular haemoglobin concentration (MCHC) (p < 0.001). Anserine preserves cellular homoeostasis through enhanced antioxidant activity and protects cell integrity in healthy men, which is important for chronic disease prevention. However, anserine temporal elevated exercise-induced cell-damage, together with enhanced antioxidant activity and haematological responses suggest an augmented exercise-induced adaptative response and recovery.
Decreased Consumption of Added Fructose Reduces Waist Circumference and Blood Glucose Concentration in Patients with Overweight and Obesity. The DISFRUTE Study: A Randomised Trial in Primary Care
Authors: Domínguez-Coello Santiago , Carrillo-Fernández Lourdes , Gobierno-Hernández Jesús , Méndez-Abad Manuel , Borges-Álamo Carlos , García-Dopico José Antonio , Aguirre-Jaime Armando , Cabrera-de León Antonio
Published: April 2020

The relationship between fructose intake and insulin resistance remains controversial. Our purpose was to determine whether a reduction in dietary fructose is effective in decreasing insulin resistance (HOMA2-IR). This field trial was conducted on 438 adults with overweight and obese status, without diabetes. A total of 121 patients in a low fructose diet (LFD) group and 118 in a standard diet (SD) group completed the 24-week study. Both diets were prescribed with 30–40% of energy intake restriction. There were no between-group differences in HOMA2-IR. However, larger decreases were seen in the LFD group in waist circumference (−7.0 vs. −4.8 = −2.2 cms, 95% CI: −3.7, −0.7) and fasting blood glucose −0.25 vs. −0.11 = −0.14 mmol/L, 95% CI: −0.028, −0.02). The percentage of reduction in calorie intake was similar. Only were differences observed in the % energy intake for some nutrients: total fructose (−2 vs. −0.6 = −1.4, 95% CI: −2.6, −0.3), MUFA (−1.7 vs. −0.4 = −1.3, 95% CI: −2.4, −0.2), protein (5.1 vs. 3.6 = 1.4, 95% CI: 0.1, 2.7). The decrease in fructose consumption originated mainly from the reduction in added fructose (−2.8 vs. −1.9 = −0.9, 95% CI: −1.6, −0.03). These results were corroborated after multivariate adjustments. The low fructose diet did not reduce insulin resistance. However, it reduced waist circumference and fasting blood glucose concentration, which suggests a decrease in hepatic insulin resistance.
Dissolving Microneedles for Rapid and Painless Local Anesthesia
Authors: Lee Byeong-Min , Lee Chisong , Lahiji Shayan Fakhraei , Jung Ui-Won , Chung Gehoon , Jung Hyungil
Published: April 2020

Microneedles are emerging drug delivery methods for painless treatment. The current study tested dissolving microneedles containing lidocaine (Li-DMN) for use in local anesthesia. An Li-DMN patch was fabricated by centrifugal lithography with carboxymethyl cellulose as a structural polymer and assessed for physical properties by optical microscopy and a fracture force analyzer. The biocompatibility was evaluated by a histology section in vitro and by ear thickness in vivo. The efficacy of the Li-DMN patch was assessed by electrophysiological recordings in primary cultured sensory neurons in vitro and a von Frey test on rats’ hind paws in vivo. The physical properties of the microneedle showed enough rigidity for transdermal penetration. The maximal capacity of lidocaine-HCl in the Li-DMN patch was 331.20 ± 6.30 µg. The cytotoxicity of the dissolving microneedle to neuronal cells was negligible under an effective dose of lidocaine for 18 h. Electrophysiological recordings verified the inhibitory effect of the voltage-gated sodium channel current by the Li-DMN patch in vitro. A skin reaction to the edema test and histologic analysis of the rats’ ears after application of the Li-DMN patch were negligible. Also, the application of the Li-DMN patch reduced the nocifensive behavior of the rats almost immediately. In conclusion, the dissolving microneedle patch with carboxymethyl cellulose is a promising candidate method for the painless delivery of lidocaine-HCl.
Carminic Acid Linked to Silica Nanoparticles as Pigment/Antioxidant Bifunctional Excipient for Pharmaceutical Emulsions
Authors: Arriagada Francisco , Ugarte Catalina , Günther Germán , Larraín María Angélica , Guarnizo-Herrero Víctor , Nonell Santi , Morales Javier
Published: April 2020

The incorporation of pigments and natural polyphenols into inorganic matrices, resulting in a hybrid material that improves the resistance and chemical stability of the pigments and the antioxidant capacity of the materials, has been of great interest to the pharmaceutical, chemical and food industries. The aim of this work was to prepare and characterize a bifunctional pigment–antioxidant nanomaterial-based carminic acid-decorated solid core-mesoporous shell silica nanoparticles, evaluating its properties as a pigment, its antioxidant capacity and its properties as a chemical stabilizer of emulsions. The chemical stability of oil-in-water (O/W) Pickering emulsions was evaluated determining the stability of vitamin E solubilized in the oil phase. Carminic acid was attached through the action of coupling ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) agents, and the resulting spherical and homogeneous nanoparticles showed a diameter close to 175 nm. A notorious change of emulsion color was observed by the addition of the nanomaterial. Emulsions showed an attractive pink color, and when the pH was adjusted to pH 3 and pH 9, a change in color was observed, analogous to carminic acid in solution. The nanomaterial incorporation also improved chemical stability, decreasing vitamin E consumption to 9.26% of the initial value, demonstrating an important antioxidant effect of the developed nanomaterial.
Melt Amorphisation of Orlistat with Mesoporous Silica Using a Supercritical Carbon Dioxide: Effects of Pressure, Temperature, and Drug Loading Ratio and Comparison with Other Conventional Amorphisation Methods
Authors: Park Heejun , Cha Kwang-Ho , Hong Seung Hyeon , Abuzar Sharif Md , Ha Eun-Sol , Kim Jeong-Soo , Kim Min-Soo , Hwang Sung-Joo
Published: April 2020

The aim of this work was to develop an amorphous orlistat-loaded mesoporus silica formulation using the melt-amorphisation by supercritical fluid (MA-SCF) and to investigate the effects of pressure and temperature on the pharmaceutical properties of the developed formulation. In addition, the effect of orlistat mass ratio to the mesoporus silica was also evaluated. The carbon dioxide was used as a supercritical fluid, and Neusilin®UFL2 was selected as the mesoporous silica. For comparison with conventional amorphisation methods, orlistat formulations were also prepared by solvent evaporation and hot melt methods. Various pharmaceutical evaluations including differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, specific surface area, total pore volume, and content uniformity were performed to characterise the prepared orlistat formulation. The melting point depression and the solubility of orlistat in supercritical carbon dioxide (SC-CO2) were selected for the interpretation of evaluated results in relation to temperature and pressure. The total pore volume of the prepared orlistat-loaded mesoporus silica decreased with an increasing density of SC-CO2 to about 500 g/L at a constant temperature or pressure. From these results, it was suggested that increasing the density of SC-CO2 to about 500 g/L could result in the easier penetration of CO2 into molten orlistat and lower viscosity, hence facilitating the introduction and loading of orlistat into the pores of Neusilin®UFL2. However, when the density of SC-CO2 increased to more than 500 g/L, the total pore volume increased, and this may be due to the release out of orlistat from the pores of Neusilin®UFL2 by the increased orlistat solubility in SC-CO2. Interestingly, as the total pore volume decreased by the filling of the drug, the drug crystallinity decreased; hence, the dissolution rate increased. Furthermore, it was shown that the most desirable mass ratio of Neusilin®UFL2:orlistat for the amorphisation was 1:0.8 at an optimised supercritical condition of 318 K and 10 MPa. Compared with other amorphisation methods, only the sample prepared by the MA-SCF method was in pure amorphous state with the fastest dissolution rate. Therefore, it was concluded that the amorphous orlistat-loaded mesoporus silica prepared using MA-SCF under optimised conditions was more advantageous for enhancing the dissolution rate of orlistat than other conventional amorphisation methods.
Stability and Safety Traits of Novel Cyclosporine A and Tacrolimus Ophthalmic Galenic Formulations Involved in Vernal Keratoconjunctivitis Treatment by a High-Resolution Mass Spectrometry Approach
Authors: Ghiglioni Daniele Giovanni , Martino Piera Anna , Bruschi Gaia , Vitali Davide , Osnaghi Silvia , Corti Maria Grazia , Beretta Giangiacomo
Published: April 2020

In this study, a sensitive quantitative method based on high performance liquid chromatography combined with high-resolution mass spectrometry, Q ExactiveTM-Orbitrap® was set up and applied for the determination of the immunosuppressor agents cyclosporine A and tacrolimus in novel ethanol-free ophthalmic formulations for the treatment of Vernal keratoconjunctivitis. Different storage parameters in terms of storage temperatures and practical usage conditions were investigated to assess the stability of all formulations during shelf life simulating the real conditions as well to confirm the feasibility of use of ethanol-free products. The methodology was linear (r2 = 0.995) over the concentration range 0–200 ng/mL, and its selectivity, precision, accuracy and recovery were all within the required limits. Under different conditions (storage period 0–90 days, 5–25 °C, unopened/usage simulated conditions), our results revealed that both active pharmaceutical ingredients (API) show satisfactory stability up to 30 days of storage/usage, with a significant and consistent concentration decline of cyclosporine A after this time point when its hydroalcoholic formulation was kept at 25 °C.
Metabolomics Response for Drought Stress Tolerance in Chinese Wheat Genotypes (Triticum aestivum)
Authors: Guo Xiaoyang , Xin Zeyu , Yang Tiegang , Ma Xingli , Zhang Yang , Wang Zhiqiang , Ren Yongzhe , Lin Tongbao
Published: April 2020

Metabolomics is an effective biotechnological tool that can be used to attain comprehensive information on metabolites. In this study, the profiles of metabolites produced by wheat seedlings in response to drought stress were investigated using an untargeted approach with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to determine various physiological processes related to drought tolerance from the cross between drought-tolerant genotype (HX10) and drought-sensitive genotype (YN211). The current study results showed that under drought stress, HX10 exhibited higher growth indices than YN211. After drought stress treatment, a series of phenolics accumulated higher in HX10 than in YN211, whereas the amount of thymine, a pyrimidine, is almost 13 folds of that in YN211. These metabolites, as well as high levels of different amino acids, alkaloids, organic acids, and flavonoids in the drought treated HX10 could help to explain its strong drought-tolerant capacity. The current study explored the understanding of the mechanisms involved in the drought response of wheat seedling; these metabolome data could also be used for potential QTL or GWAS studies to identify locus (loci) or gene(s) associated with these metabolic traits for the crop improvement.
Fabrication of Poly(vinyl alcohol)-Polyaniline Nanofiber/Graphene Hydrogel for High-Performance Coin Cell Supercapacitor
Authors: Joo Hyeonseo , Han Hoseong , Cho Sunghun
Published: April 2020

Electroactive polymer hydrogel offers several advantages for electrical devices, including straightforward synthesis, high conductivity, excellent redox behavior, structural robustness, and outstanding mechanical properties. Here, we report an efficient strategy for generating polyvinyl alcohol–polyaniline–multilayer graphene hydrogels (PVA–PANI–MLG HDGs) with excellent scalability and significantly improved mechanical, electrical, and electrochemical properties; the hydrogels were then utilized in coin cell supercapacitors. Production can proceed through the simple formation of boronate (–O–B–O–) bonds between PANI and PVA chains; strong intermolecular interactions between MLG, PANI, and PVA chains contribute to stronger and more rigid HDGs. We identified the optimal amount of PVA (5 wt.%) that produces a nanofiber-like PVA–PANI HDG with better charge transport properties than PANI HDGs produced by earlier approaches. The PVA–PANI–MLG HDG demonstrated superior tensile strength (8.10 MPa) and higher specific capacitance (498.9 F/cm2, 166.3 F/cm3, and 304.0 F/g) than PVA–PANI HDGs without MLG. The remarkable reliability of the PVA–PANI–MLG HDG was demonstrated by 92.6% retention after 3000 cycles of galvanostatic charge–discharge. The advantages of this HDG mean that a coin cell supercapacitor assembled using it is a promising energy storage device for mobile and miniaturized electronics.