bluuebunny/crossref_metadata_2025 huggingface dataset:
In Silico Study Identified Methotrexate Analog as Potential Inhibitor of Drug Resistant Human Dihydrofolate Reductase for Cancer Therapeutics
Authors: Rana Rabia Mukhtar , Rampogu Shailima , Abid Noman Bin , Zeb Amir , Parate Shraddha , Lee Gihwan , Yoon Sanghwa , Kim Yumi , Kim Donghwan , Lee Keun Woo
Published: August 2020

Drug resistance is a core issue in cancer chemotherapy. A known folate antagonist, methotrexate (MTX) inhibits human dihydrofolate reductase (hDHFR), the enzyme responsible for the catalysis of 7,8-dihydrofolate reduction to 5,6,7,8-tetrahydrofolate, in biosynthesis and cell proliferation. Structural change in the DHFR enzyme is a significant cause of resistance and the subsequent loss of MTX. In the current study, wild type hDHFR and double mutant (engineered variant) F31R/Q35E (PDB ID: 3EIG) were subject to computational study. Structure-based pharmacophore modeling was carried out for wild type (WT) and mutant (MT) (variant F31R/Q35E) hDHFR structures by generating ten models for each. Two pharmacophore models, WT-pharma and MT-pharma, were selected for further computations, and showed excellent ROC curve quality. Additionally, the selected pharmacophore models were validated by the Guner-Henry decoy test method, which yielded high goodness of fit for WT-hDHFR and MT-hDHFR. Using a SMILES string of MTX in ZINC15 with the selections of ‘clean’, in vitro and in vivo options, 32 MTX-analogs were obtained. Eight analogs were filtered out due to their drug-like properties by applying absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment tests and Lipinski’s Rule of five. WT-pharma and MT-pharma were further employed as a 3D query in virtual screening with drug-like MTX analogs. Subsequently, seven screening hits along with a reference compound (MTX) were subjected to molecular docking in the active site of WT- and MT-hDHFR. Through a clustering analysis and examination of protein-ligand interactions, one compound was found with a ChemPLP fitness score greater than that of MTX (reference compound). Finally, a simulation of molecular dynamics (MD) identified an MTX analog which exhibited strong affinity for WT- and MT-hDHFR, with stable RMSD, hydrogen bonds (H-bonds) in the binding site and the lowest MM/PBSA binding free energy. In conclusion, we report on an MTX analog which is capable of inhibiting hDHFR in wild type form, as well as in cases where the enzyme acquires resistance to drugs during chemotherapy treatment.
Novel Validated Analytical Method Based on Potentiometric Transduction for the Determination of Citicoline Psychostimulant/Nootropic Agent
Authors: Kamel Ayman H. , Amr Abd El-Galil E. , Galal Hoda R. , Almehizia Abdulrahman A.
Published: August 2020

Herein, a novel validated potentiometric method is presented for the first time for citicoline determination. The method is based on measuring the potential using new constructed citicoline electrodes. The electrodes are based on the use of citicolinium/phosphomolybdate [Cit]2[PM] (sensor I) and citicolinium/tetraphenylborate [Cit][TPB] (sensor II) ion association complexes. These sensory materials were dispersed in plasticized polyvinyl chloride (PVC) polymeric membranes. The sensors revealed a Nernstian response with the slopes 55.9 ± 1.8(r2 = 0.9994) and 51.8 ± 0.9 (r2 = 0.9991) mV/decade over a linearity range of 6.3 × 10−6–1.0 × 10−3 and 1.0 × 10−5–1.0 × 10−3 M and detection limits of 3.16 × 10−6 and 7.1 × 10−6 M for sensors I and II, respectively. To ensure the existence of monovalent citicoline, all measurements were performed in 50 mM acetate buffer at pH 3.5. All presented electrodes showed good performance characteristics such as rapid response, good selectivity, high potential-stability and long life-span. Method verification and validation in terms of response linearity, quantification limit, accuracy, bias, trueness, robustness, within-day variability and between-days variability were evaluated. The method was introduced for citicoline determination in different pharmaceutical formulations and compared with the standard high performance liquid chromatography (HPLC) method.
Optimization of a Simplified and Effective Analytical Method of Pesticide Residues in Mealworms (Tenebrio molitor Larvae) Combined with GC–MS/MS and LC–MS/MS
Authors: Kim Leesun , Baek Sujin , Son Kyungae , Kim Eunsun , Noh Hyun Ho , Kim Danbi , Oh Min-seok , Moon Byeong-chul , Ro Jin-Ho
Published: August 2020

An effective analytical method was optimized for residues including chlorpyrifos–methyl, deltamethrin, fenoxanil, thiobencarb and fludioxonil in mealworms, the larval form of Tenebrio molitor. They are listed for pest control during wheat cultivation and can be found in wheat-bran feed for growing mealworms in South Korea. Analytes were extracted using acetonitrile and salt packet. Four clean-up methods ((1) MgSO4 + 25 mg PSA + 25 mg C18; (2) MgSO4 + 50 mg PSA + 50 mg C18; (3) EMR-lipidTM tube; and (4) 10 mL n-hexane) were investigated and the method (1) was selected due to its robustness. Low-temperature precipitation of fat and proteins improved the recoveries. Recoveries from the Method (1) were satisfying with 70–120% with <20% relative SD at a spiking level of 0.01 mg/kg. With the simultaneous sample preparation, fenoxanil, thiobencarb and fludioxonil were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS) and chlorpyrifos–methyl and deltamethrin by gas chromatography tandem mass spectrometry (GC–MS/MS). Quantification limits for LC–MS/MS and GC–MS/MS were 0.5 and 2.5 μg/L, respectively. No pesticides of interest were detected in 30 real samples collected across the nation. However, the data can be provided for establishing maximum residue limits for the pesticides in mealworms in response to the positive list system.
i-Propylammonium Lead Chloride Based Perovskite Photocatalysts for Depolymerization of Lignin Under UV Light
Authors: Kausar Samia , Altaf Ataf Ali , Hamayun Muhammad , Rasool Nasir , Hadait Mahwish , Akhtar Arusa , Muhammad Shabbir , Badshah Amin , Shah Syed Adnan Ali , Zakaria Zainul Amiruddin
Published: August 2020

Lignin depolymerization for the purpose of synthesizing aromatic molecules is a growing focus of research to find alternative energy sources. In current studies, the photocatalytic depolymerization of lignin has been investigated by two new iso-propylamine-based lead chloride perovskite nanomaterials (SK9 and SK10), synthesized by the facile hydrothermal method. Characterization was done by Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), UV-Visible (UV-Vis), Photoluminescence (PL), and Fourier-Transform Infrared (FTIR) Spectroscopy and was used for the photocatalytic depolymerization of lignin under UV light. Lignin depolymerization was monitored by taking absorption spectra and catalytic paths studied by applying kinetic models. The %depolymerization was calculated for factors such as catalyst dose variation, initial concentration of lignin, and varying temperatures. Pseudo-second order was the best suited kinetic model, exhibiting a mechanism for lignin depolymerization that was chemically rate controlled. The activation energy (Ea) for the depolymerization reaction was found to be 15 kJ/mol, which is remarkably less than conventional depolymerization of the lignin, i.e., 59.75 kJ/mol, exhibiting significant catalytic efficiencies of synthesized perovskites. Products of lignin depolymerization obtained after photocatalytic activity at room temperature (20 °C) and at 90 °C were characterized by GC-MS analysis, indicating an increase in catalytic lignin depolymerization structural subunits into small monomeric functionalities at higher temperatures. Specifically, 2-methoxy-4-methylphenol (39%), benzene (17%), phenol (10%) and catechol (7%) were detected by GC-MS analysis of lignin depolymerization products.
Selective Arylation of 2-Bromo-4-chlorophenyl-2-bromobutanoate via a Pd-Catalyzed Suzuki Cross-Coupling Reaction and Its Electronic and Non-Linear Optical (NLO) Properties via DFT Studies
Authors: Nazeer Usman , Rasool Nasir , Mujahid Aqsa , Mansha Asim , Zubair Muhammad , Kosar Naveen , Mahmood Tariq , Raza Shah Ali , Shah Syed Adnan Ali , Zakaria Zainul Amiruddin , Akhtar Muhammad Nadeem
Published: August 2020

In the present study, 2-bromo-4-chlorophenyl-2-bromobutanoate (3) was synthesized via the reaction of 2-bromo-4-chlorophenol with 2-bromobutanoyl bromide in the presence of pyridine. A variety of 2-bromo-4-chlorophenyl-2-bromobutanoate derivatives (5a–f) were synthesized with moderate to good yields via a Pd-catalyzed Suzuki cross-coupling reaction. To find out the reactivity and electronic properties of the compounds, Frontier molecular orbital analysis, non-linear optical properties, and molecular electrostatic potential studies were performed.
Synergistic Effect of a Pleuromutilin Derivative with Tetracycline against Streptococcus suis In Vitro and in the Neutropenic Thigh Infection Model
Authors: Chen Fang , Wei Meng-Chao , Luo Yi-Dan , Jin Zhen , Tang You-Zhi
Published: August 2020

Tetracycline (TET) has been widely used in the treatment of Streptococcus suis (S. suis) infection. However, it was found that the efficacy of many antibiotics in S. suis decreased significantly, especially tetracycline. In this study, GML-12 (a novel pleuromutilin derivative) was used in combination with TET against 12 S. suis isolates. In the checkerboard assay, the TET/GML-12 combination exhibited synergistic and additive effects against S. suis isolates (n = 12). In vitro time-killing assays and in vivo therapeutic experiments were used to confirm the synergistic effect of the TET/GML-12 combination against S. suis strains screened based on an FICI ≤ 0.5. In time-killing assays, the TET/GML-12 combination showed a synergistic effect or an additive effect against three isolates with a bacterial reduction of over 2.4-log10 CFU/mL compared with the most active monotherapy. Additionally, the TET/GML-12 combination displayed potent antimicrobial activity against four isolates in a mouse thigh infection model. These results suggest that the TET/GML-12 combination may be a potential therapeutic strategy for S. suis infection.
Identification of Polyphenols from Coniferous Shoots as Natural Antioxidants and Antimicrobial Compounds
Authors: Dziedzinski Marcin , Kobus-Cisowska Joanna , Szymanowska Daria , Stuper-Szablewska Kinga , Baranowska Marlena
Published: August 2020

Currently, coniferous shoots are almost absent as a food ingredient despite their wide availability in many parts of the world. The aim of the study was to assess and compare the composition of selected plant metabolites, evaluate the antioxidant and antimicrobial properties of selected shoots collected in 2019 from the arboretum in Zielonka (Poland), including individual samples from Picea abies L. (PA), Larix decidua Mill (LD), Pinus sylvestris L. (PS), Pseudotsuga menziesii (PM) and Juniperus communis L. (JC). The present work has shown that aqueous extracts obtained from tested shoots are a rich source of phenols such as caffeic acid, ferulic acid, chlorogenic acid, 4-hydroxybenzoic acid and many others. Obtained extracts exhibit antioxidant and antimicrobial properties in vitro. The highest sum of the studied phenolic compounds was found in the PA sample (13,947.80 µg/g dw), while the lowest in PS (6123.57 µg/g dw). The samples were particularly rich in ferulic acid, chlorogenic acid and 4-hydroxybenzoic acid. The highest values regarding the Folin-Ciocâlteu reagent (FCR) and ferric reducing ability of plasma (FRAP) reducing ability tests, as well as the total flavonoid content assay, were obtained for the LD sample, although the LD (14.83 mg GAE/g dw) and PM (14.53 mg GAE/g dw) samples did not differ statistically in the FCR assay. With respect to free radical quenching measurements (DPPH), the PA (404.18-μM Trolox/g dw) and JC (384.30-μM Trolox/g dw) samples had the highest radical quenching ability and did not differ statistically. Generally, extracts obtained from PA and PS showed the highest antimicrobial activity against tested Gram-negative bacteria, Gram-positive bacteria and fungi.
Bioactive Compounds, Antioxidant Activity, and Antinutritional Content of Legumes: A Comparison between Four Phaseolus Species
Authors: Alcázar-Valle Montserrat , Lugo-Cervantes Eugenia , Mojica Luis , Morales-Hernández Norma , Reyes-Ramírez Heidy , Enríquez-Vara Jhony Navat , García-Morales Soledad
Published: August 2020

Beans (Phaseolus spp.) are one of the most important legumes for their nutritional value and health benefits in many world regions. In addition to Phaseolus vulgaris, there are four additional species that are cultivated in many regions of the world and are a source of food for human consumption: P. lunatus, P. coccineus, P. polyanthus, and P. acutifolius. In this work, phenolic compounds, antioxidant activity, and anti-nutritional compounds of 18 bean accessions, corresponding to four different species of the genus Phaseolus, were analyzed. In addition, their physical characteristics, proximate composition, and amino acid content were determined in order to compare their phytochemical composition and nutritional value. The species closest to each other in terms of essential amino acid content were P. polyanthus with P. vulgaris and P. lunatus with P. coccineus. Furthermore, there was a strong positive correlation between antioxidant activity and flavonoids, anthocyanins, and lectins with all the accessions collected. Significant differences in the content of phenolic compounds were found among the bean species studied. Therefore, in addition to P. vulgaris, other species such as P. coccineus and P. lunatus have high biological and antioxidant potential that could be beneficial to human health when consumed as nutraceutical foods.
GC-MS Phytochemical Profiling, Pharmacological Properties, and In Silico Studies of Chukrasia velutina Leaves: A Novel Source for Bioactive Agents
Authors: Jahan Israt , Tona Marzia Rahman , Sharmin Sanjida , Sayeed Mohammed Aktar , Tania Fatamatuz Zuhura , Paul Arkajyoti , Chy Md. Nazim Uddin , Rakib Ahmed , Emran Talha Bin , Simal-Gandara Jesus
Published: August 2020

Chukrasia velutina is a local medicinal plant commonly known as chikrassy in Bangladesh, India, China, and other South Asian countries. The leaves, bark, and seeds are vastly used as herbal medicine for fever and diarrhea, and its leaves essential oils are used for antimicrobial purposes. In this study, we discuss the neuropsychiatric properties of C. velutina leaves through several animal models, quantitative and qualitative phytochemical analysis, and computational approaches. Neuropsychiatric effects were performed in rodents on the methanolic extract of C. velutina leaves (MECVL). Antidepressant, anxiolytic, and sedative effects experimented through these rodent models were used such as the force swimming test (FST), tail suspension test (TST), hole board test (HBT), elevated plus maze test (EPMT), light/dark box test (LDBT), open field test (OFT), and hole cross test (HCT). In these rodent models, 200 and 400 mg/kg doses were used which exhibited a significant result in the force swimming and tail suspension test (p < 0.001) for the antidepressant effect. In the anxiolytic study, the results were significant in the hole board, elevated plus maze, and light/dark box test (p < 0.001) for doses of 200 and 400 mg/kg. The result was also significant in the open field and hole cross test (p < 0.001) for sedative action in the sake of similar doses. Moreover, qualitative and quantitative studies were also performed through phytochemical screening and GC-MS analysis, and fifty-seven phytochemical compounds were found. These compounds were analyzed for pharmacokinetics properties using the SwissADME tool and from them, thirty-five compounds were considered for the molecular docking analysis. These phytoconstituents were docking against the human serotonin receptor, potassium channel receptor, and crystal structure of human beta-receptor, where eight of the compounds showed a good binding affinity towards the respective receptors considered to the reference standard drugs. After all of these analyses, it can be said that the secondary metabolite of C. velutina leaves (MECVL) could be a good source for inhibiting the neuropsychiatric disorders which were found on animal models as well as in computational studies.
Streptomyces sp. Strain MUSC 125 from Mangrove Soil in Malaysia with Anti-MRSA, Anti-Biofilm and Antioxidant Activities
Authors: Mangzira Kemung Hefa , Tan Loh Teng-Hern , Chan Kok-Gan , Ser Hooi-Leng , Law Jodi Woan-Fei , Lee Learn-Han , Goh Bey-Hing
Published: August 2020

There is an urgent need to search for new antibiotics to counter the growing number of antibiotic-resistant bacterial strains, one of which is methicillin-resistant Staphylococcus aureus (MRSA). Herein, we report a Streptomyces sp. strain MUSC 125 from mangrove soil in Malaysia which was identified using 16S rRNA phylogenetic and phenotypic analysis. The methanolic extract of strain MUSC 125 showed anti-MRSA, anti-biofilm and antioxidant activities. Strain MUSC 125 was further screened for the presence of secondary metabolite biosynthetic genes. Our results indicated that both polyketide synthase (pks) gene clusters, pksI and pksII, were detected in strain MUSC 125 by PCR amplification. In addition, gas chromatography-mass spectroscopy (GC-MS) detected the presence of different chemicals in the methanolic extract. Based on the GC-MS analysis, eight known compounds were detected suggesting their contribution towards the anti-MRSA and anti-biofilm activities observed. Overall, the study bolsters the potential of strain MUSC 125 as a promising source of anti-MRSA and antibiofilm compounds and warrants further investigation.
Hydrogel Containing Anti-CD44-Labeled Microparticles, Guide Bone Tissue Formation in Osteochondral Defects in Rabbits
Authors: Filová Eva , Tonar Zbyněk , Lukášová Věra , Buzgo Matěj , Litvinec Andrej , Rampichová Michala , Beznoska Jiří , Plencner Martin , Staffa Andrea , Daňková Jana , Soural Miroslav , Chvojka Jiří , Malečková Anna , Králíčková Milena , Amler Evžen
Published: August 2020

Hydrogels are suitable for osteochondral defect regeneration as they mimic the viscoelastic environment of cartilage. However, their biomechanical properties are not sufficient to withstand high mechanical forces. Therefore, we have prepared electrospun poly-ε-caprolactone-chitosan (PCL-chit) and poly(ethylene oxide)-chitosan (PEO-chit) nanofibers, and FTIR analysis confirmed successful blending of chitosan with other polymers. The biocompatibility of PCL-chit and PEO-chit scaffolds was tested; fibrochondrocytes and chondrocytes seeded on PCL-chit showed superior metabolic activity. The PCL-chit nanofibers were cryogenically grinded into microparticles (mean size of about 500 µm) and further modified by polyethylene glycol–biotin in order to bind the anti-CD44 antibody, a glycoprotein interacting with hyaluronic acid (PCL-chit-PEGb-antiCD44). The PCL-chit or PCL-chit-PEGb-antiCD44 microparticles were mixed with a composite gel (collagen/fibrin/platelet rich plasma) to improve its biomechanical properties. The storage modulus was higher in the composite gel with microparticles compared to fibrin. The Eloss of the composite gel and fibrin was higher than that of the composite gel with microparticles. The composite gel either with or without microparticles was further tested in vivo in a model of osteochondral defects in rabbits. PCL-chit-PEGb-antiCD44 significantly enhanced osteogenic regeneration, mainly by desmogenous ossification, but decreased chondrogenic differentiation in the defects. PCL-chit-PEGb showed a more homogeneous distribution of hyaline cartilage and enhanced hyaline cartilage differentiation.
Physical Investigations of (Co, Mn) Co-Doped ZnO Nanocrystalline Films
Authors: Yahmadi Bechir , Kamoun Olfa , Alhalaili Badriyah , Alleg Safia , Vidu Ruxandra , Kamoun Turki Najoua
Published: August 2020

Undoped as well as (Co, Mn) co-doped Zinc oxides have been effectively developed on glass substrates, taking advantage of the spray pyrolysis procedure. The X-ray diffraction XRD as well as X-ray photoelectron spectroscopy (XPS) measurements have recognized a pure hexagonal wurtzite form of ZnO, and no other collateral phases such as MnO2 or CoO2 have been observed as a result of doping. The calculated values of the texture coefficient (TC) were between 0.15 and 5.14, indicating a dominant orientation along the (002) plane. The crystallite size (D) varies with the (Co, Mn) contents. The dislocation density (δ) as well as the residual microstrains increased after Co and Mn doping. Furthermore, the surface morphology of the films has been affected significantly by the Co and Mn incorporation, as shown by the scanning electron microscopy (SEM) investigation. The study of the optical properties exhibits a red shift of the band gap energy (Eg) with the (Co, Mn) co-doping. The magnetic measurements have shown that the undoped and (Co, Mn) co-doped ZnO thin films displayed room-temperature ferromagnetism (RTFM).
The Puzzling Potential of Carbon Nanomaterials: General Properties, Application, and Toxicity
Authors: Jović Danica , Jaćević Vesna , Kuča Kamil , Borišev Ivana , Mrdjanovic Jasminka , Petrovic Danijela , Seke Mariana , Djordjevic Aleksandar
Published: August 2020

Being a member of the nanofamily, carbon nanomaterials exhibit specific properties that mostly arise from their small size. They have proved to be very promising for application in the technical and biomedical field. A wide spectrum of use implies the inevitable presence of carbon nanomaterials in the environment, thus potentially endangering their whole nature. Although scientists worldwide have conducted research investigating the impact of these materials, it is evident that there are still significant gaps concerning the knowledge of their mechanisms, as well as the prolonged and chronic exposure and effects. This manuscript summarizes the most prominent representatives of carbon nanomaterial groups, giving a brief review of their general physico-chemical properties, the most common use, and toxicity profiles. Toxicity was presented through genotoxicity and the activation of the cell signaling pathways, both including in vitro and in vivo models, mechanisms, and the consequential outcomes. Moreover, the acute toxicity of fullerenol, as one of the most commonly investigated members, was briefly presented in the final part of this review. Thinking small can greatly help us improve our lives, but also obliges us to deeply and comprehensively investigate all the possible consequences that could arise from our pure-hearted scientific ambitions and work.
Hydrogel as a Biomaterial for Bone Tissue Engineering: A Review
Authors: Yue Shuai , He Hui , Li Bin , Hou Tao
Published: August 2020

Severe bone damage from diseases, including extensive trauma, fractures, and bone tumors, cannot self-heal, while traditional surgical treatment may bring side effects such as infection, inflammation, and pain. As a new biomaterial with controllable mechanical properties and biocompatibility, hydrogel is widely used in bone tissue engineering (BTE) as a scaffold for growth factor transport and cell adhesion. In order to make hydrogel more suitable for the local treatment of bone diseases, hydrogel preparation methods should be combined with synthetic materials with excellent properties and advanced technologies in different fields to better control drug release in time and orientation. It is necessary to establish a complete method to evaluate the hydrogel’s properties and biocompatibility with the human body. Moreover, establishment of standard animal models of bone defects helps in studying the therapeutic effect of hydrogels on bone repair, as well as to evaluate the safety and suitability of hydrogels. Thus, this review aims to systematically summarize current studies of hydrogels in BTE, including the mechanisms for promoting bone synthesis, design, and preparation; characterization and evaluation methods; as well as to explore future applications of hydrogels in BTE.
Epitaxy from a Periodic Y–O Monolayer: Growth of Single-Crystal Hexagonal YAlO3 Perovskite
Authors: Hong Minghwei , Cheng Chao-Kai , Lin Yen-Hsun , Young Lawrence Boyu , Cai Ren-Fong , Hsu Chia-Hung , Wu Chien-Ting , Kwo Jueinai
Published: August 2020

The role of an atomic-layer thick periodic Y–O array in inducing the epitaxial growth of single-crystal hexagonal YAlO3 perovskite (H-YAP) films was studied using high-angle annular dark-field and annular bright-field scanning transmission electron microscopy in conjunction with a spherical aberration-corrected probe and in situ reflection high-energy electron diffraction. We observed the Y–O array at the interface of amorphous atomic layer deposition (ALD) sub-nano-laminated (snl) Al2O3/Y2O3 multilayers and GaAs(111)A, with the first film deposition being three cycles of ALD-Y2O3. This thin array was a seed layer for growing the H-YAP from the ALD snl multilayers with 900 °C rapid thermal annealing (RTA). The annealed film only contained H-YAP with an excellent crystallinity and an atomically sharp interface with the substrate. The initial Y–O array became the bottom layer of H-YAP, bonding with Ga, the top layer of GaAs. Using a similar ALD snl multilayer, but with the first film deposition of three ALD-Al2O3 cycles, there was no observation of a periodic atomic array at the interface. RTA of the sample to 900 °C resulted in a non-uniform film, mixing amorphous regions and island-like H-YAP domains. The results indicate that the epitaxial H-YAP was induced from the atomic-layer thick periodic Y–O array, rather than from GaAs(111)A.
Efficacy of Dietary Supplements to Reduce Liver Fat
Authors: Kilchoer Brittanie , Vils Anina , Minder Beatrice , Muka Taulant , Glisic Marija , Bally Lia
Published: August 2020

Liver fat accumulation is an important pathophysiological feature of non-alcoholic fatty liver disease that may be modulated by dietary supplements (DS). A systematic search of the literature was conducted for randomized controlled trials (RCTs) pertaining to the effect of a DS on liver fat as assessed using quantitative tomographic imaging in human adults. Where feasible, data were pooled, and meta-analyses conducted using random-effect model. Quality assessment was done according the Cochrane Collaboration’s tool for assessing risk of bias. Twenty RCTs, involving 1171 overweight and obese adults, of which 36% were females, with or without comorbidities, were included. Only RCTs assessing omega-3 fatty acids (n = 4) and resveratrol (n = 4) qualified for meta-analysis. Results did neither favor omega-3 (effect size −1.17; weighted mean difference (WMD) (95% confidence interval (CI)) −3.62, 1.28; p < 0.001) nor resveratrol supplementation (0.18; 95% CI −1.08, 1.43; p = 0.27). The findings of the qualitatively summarized RCTs suggested that catechins (n = 1), Lactobacillus reuteri (n = 1), and carnitine (n = 1) may reduce liver fat. All other DS did not show any influence. The current evidence is scarce, of limited quality and does not support DS use to reduce liver fat. Further well-designed trials are warranted.
Impact of Heat-Killed Lactobacillus casei Strain IMAU60214 on the Immune Function of Macrophages in Malnourished Children
Authors: Rocha-Ramírez Luz María , Hernández-Ochoa Beatriz , Gómez-Manzo Saúl , Marcial-Quino Jaime , Cárdenas-Rodríguez Noemí , Centeno-Leija Sara , García-Garibay Mariano
Published: August 2020

Malnutrition is commonly associated with immunological deregulation, increasing the risk of infectious illness and death. The objective of this work was to determine the in vitro effects of heat-killed Lactobacillus casei IMAU60214 on monocyte-derived macrophages (MDMs) from well-nourished healthy children, well-nourished infected children and malnourished infected children, which was evaluated by an oxygen-dependent microbicidal mechanism assay of luminol-increase chemiluminescence and the secretion of tumor necrosis factor (TNF-α), interleukin (IL-1β), IL-6 and IL-10, as well as phagocytosis using zymosan and as its antibacterial activity against Salmonella typhimurium, Escherichia coli and Staphylococcus aureus. We found that reactive oxygen species (ROS), secretion cytokines (TNFα, IL-1β, IL-6 and IL-10 levels), phagocytosis and bactericidal capacity increased in all groups after pre-treatment with heat-killed L. casei IMAU60214 at a ratio of 500:1 (bacteria:MDM) over 24 h compared with MDM cells without pre-treatment. The results could indicate that heat-killed L. casei IMAU60214 is a potential candidate for regulating the immune function of macrophages.
Dietary Patterns in Relation to Prospective Sleep Duration and Timing among Mexico City Adolescents
Authors: Jansen Erica C. , Baylin Ana , Cantoral Alejandra , Téllez Rojo Martha María , Burgess Helen J. , O'Brien Louise M. , Torres Olascoaga Libni , Peterson Karen E.
Published: August 2020

Adult studies show that healthy diet patterns relate to better sleep. However, evidence during adolescence, when sleep may change dramatically, is lacking. Within a cohort of 458 Mexican adolescents, we examined whether consumption of three dietary patterns was associated with sleep duration and timing measured 2 years later, as well as changes in sleep timing and duration. Dietary patterns (identified a posteriori in a prior analysis) were assessed with a baseline food frequency questionnaire, and sleep was measured with wrist actigraphy at baseline and follow-up. Linear regression analyses adjusting for sex, age, screen time, and smoking were conducted. Adolescents with higher consumption of a Plant-Based and Lean Proteins pattern had earlier sleep timing (−0.45 h with 95% Confidence Interval (CI) −0.81, −0.08 in the highest compared to lowest quartiles), less of a phase delay in sleep timing over follow-up (−0.39 h with 95% CI −0.80, 0.02), and shorter weekend sleep duration (0.5 h with 95% CI −0.88, −0.1). Higher consumption of an Eggs, Milk and Refined Grain pattern was associated with earlier sleep timing (−0.40 h with 95% CI −0.77, −0.04), while consumption of a Meat and Starchy pattern was related to higher social jetlag (weekend–weekday sleep timing difference). Healthier diet patterns may promote better sleep in adolescents.
Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters
Authors: Mohos Violetta , Fliszár-Nyúl Eszter , Ungvári Orsolya , Kuffa Katalin , Needs Paul W. , Kroon Paul A. , Telbisz Ágnes , Özvegy-Laczka Csilla , Poór Miklós
Published: August 2020

Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can interact with several proteins of pharmacokinetic importance. However, the interactions of its metabolites with biotransformation enzymes and drug transporters have barely been examined. In this study, the inhibitory effects of quercetin and its most relevant methyl, sulfate, and glucuronide metabolites were tested on cytochrome P450 (CYP) (2C19, 3A4, and 2D6) enzymes as well as on organic anion-transporting polypeptides (OATPs) (OATP1A2, OATP1B1, OATP1B3, and OATP2B1) and ATP (adenosine triphosphate) Binding Cassette (ABC) (BCRP and MRP2) transporters. Quercetin and its metabolites (quercetin-3′-sulfate, quercetin-3-glucuronide, isorhamnetin, and isorhamnetin-3-glucuronide) showed weak inhibitory effects on CYP2C19 and 3A4, while they did not affect CYP2D6 activity. Some of the flavonoids caused weak inhibition of OATP1A2 and MRP2. However, most of the compounds tested proved to be strong inhibitors of OATP1B1, OATP1B3, OATP2B1, and BCRP. Our data demonstrate that not only quercetin but some of its conjugates, can also interact with CYP enzymes and drug transporters. Therefore, high intake of quercetin may interfere with the pharmacokinetics of drugs.
“It’s Important but, on What Level?”: Healthy Cooking Meanings and Barriers to Healthy Eating among University Students
Authors: Vélez-Toral Mercedes , Rodríguez-Reinado Carmen , Ramallo-Espinosa Ana , Andrés-Villas Montserrat
Published: August 2020

The negative impact of a sedentary lifestyle and poor diet on health is evident across the lifespan, but particularly during the university period. Usually, the diet of university students is rich in sweetened drinks and processed foods and low in fruits, vegetables and legumes. Although there is an association between maintaining a healthy diet and the frequency of cooking at home, the time currently spent on cooking or learning how to cook is decreasing globally. The main aim of this study was to explore university students’ perceptions about healthy cooking and barriers to eating healthily. A group of 26 students participated in four focus groups. Content analysis was conducted using Atlas.ti v.8. Students perceived cooking healthily as a more complicated and time-consuming process than cooking in general. Individual and environmental factors were the most reported barriers. Costs and time, among others, were the main barriers pointed out by students with regard to healthy eating. This study highlights the need to develop interventions that modify these false perceptions about cooking healthily, and to train students so that they are able to cook healthy meals in a quick, easy, and cost-effective way. Further, specific actions are required in the university setting to minimize access to unhealthy options and to promote those linked to healthy eating.
Association between the Phytochemical Index and Lower Prevalence of Obesity/Abdominal Obesity in Korean Adults
Authors: Im Jihyun , Kim Minkyeong , Park Kyong
Published: August 2020

The relatively high levels of vegetable consumption have highlighted the need to examine the association between phytochemical intake and disease prevention. We examined the association between the phytochemical index (PI) and obesity/abdominal obesity among Korean adults. We analyzed the data of 57,940 adults aged ≥ 19 years obtained from the Korea National Health and Nutrition Examination Survey. We calculated PI using the 24 h recall data, and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. Dose–response patterns were analyzed using restricted cubic spline regression. After multivariable adjustment, a higher PI was found to be associated with a lower prevalence of obesity and abdominal obesity; this association was notable in women (obesity, OR: 0.86, CI: 0.78–0.94, p for trend = 0.01; abdominal obesity, OR: 0.81, CI: 0.73–0.90, p for trend < 0.001). Spline regression showed linearity of the associations between PI and obesity/abdominal obesity in women. Our findings suggested that maintaining a phytochemical-rich diet may help to prevent obesity and abdominal obesity, especially in women, as an increased PI corresponded to lower prevalence of obesity. This study, using evidence-based data, highlighted the importance of consuming plant-derived foods to prevent obesity.
Assessing the Cost-Effectiveness of Interventions That Simultaneously Prevent High Body Mass Index and Eating Disorders
Authors: Le Long Khanh-Dao , Hay Phillipa , Ananthapavan Jaithri , Lee Yong Yi , Mihalopoulos Cathrine
Published: August 2020

Eating disorders (ED) are among the top three most common debilitating illnesses in adolescent females, while high Body Mass Index (BMI) is one of the five leading modifiable risk factors for preventable disease burden. The high prevalence of eating and weight-related problems in adolescence is of great concern, particularly since this is a period of rapid growth and development. Here, we comment on the current evidence for the prevention of EDs and high BMI and the importance of assessing the cost-effectiveness of interventions that integrate the prevention of EDs and high BMI in this population. There is evidence that there are effective interventions targeted at children, adolescents and young adults that can reduce the prevalence of risk factors associated with the development of EDs and high BMI concurrently. However, optimal decision-making for the health of younger generations involves considering the value for money of these effective interventions. Further research investigating the cost-effectiveness of potent and sustainable integrated preventive interventions for EDs and high BMI will provide decision makers with the necessary information to inform investment choices.
Gestational Weight Gain—Re-Examining the Current Paradigm
Authors: Louise Jennie , Deussen Andrea R. , Dodd Jodie M.
Published: August 2020

Our aim was to investigate the underlying assumptions of the current gestational weight gain (GWG) paradigm, specifically that—(1) GWG is modifiable through diet and physical activity; (2) optimal GWG and risk of excess GWG, vary by pre-pregnancy body mass index (BMI) category and (3) the association between GWG and adverse pregnancy outcomes is causal. Using data from three large, harmonized randomized controlled trials (RCTs) of interventions to limit GWG and improve pregnancy outcomes and with appropriate regression models, we investigated the link between diet and physical activity and GWG; the relationships between pre-pregnancy BMI, GWG and birth weight z-score; and the evidence for a causal relationship between GWG and pregnancy outcomes. We found little evidence that diet and physical activity in pregnancy affected GWG and that the observed relationships between GWG and adverse pregnancy outcomes are causal in nature. Further, while there is evidence that optimal GWG may be lower for women with higher BMI, target ranges defined by BMI categories do not accurately reflect risk of adverse outcomes. Our findings cast doubt upon current advice regarding GWG, particularly for overweight and obese women and suggest that a change in focus is warranted.
Current Evidence on the Efficacy of Gluten-Free Diets in Multiple Sclerosis, Psoriasis, Type 1 Diabetes and Autoimmune Thyroid Diseases
Authors: Passali Moschoula , Josefsen Knud , Frederiksen Jette Lautrup , Antvorskov Julie Christine
Published: August 2020

In this review, we summarize the clinical data addressing a potential role for gluten in multiple sclerosis (MS), psoriasis, type 1 diabetes (T1D) and autoimmune thyroid diseases (ATDs). Furthermore, data on the prevalence of celiac disease (CD) and gluten-related antibodies in the above patient groups are presented. Adequately powered and properly controlled intervention trials investigating the effects of a gluten-free diet (GFD) in non-celiac patients with MS, psoriasis, T1D or ATDs are lacking. Only one clinical trial has studied the effects of a GFD among patients with MS. The trial found significant results, but it is subject to major methodological limitations. A few publications have found beneficial effects of a GFD in a subgroup of patients with psoriasis that were seropositive for anti-gliadin or deamidated gliadin antibodies, but no effects were seen among seronegative patients. Studies on the role of gluten in T1D are contradictive, however, it seems likely that a GFD may contribute to normalizing metabolic control without affecting levels of islet autoantibodies. Lastly, the effects of a GFD in non-celiac patients with ATDs have not been studied yet, but some publications report that thyroid-related antibodies respond to a GFD in patients with concomitant CD and ATDs. Overall, there is currently not enough evidence to recommend a GFD to non-celiac patients with MS, psoriasis, ATDs or T1D.
Adenosine Receptor Agonists Increase the Inhibition of Platelet Function by P2Y12 Antagonists in a cAMP- and Calcium-Dependent Manner
Authors: Wolska Nina , Kassassir Hassan , Luzak Boguslawa , Watala Cezary , Rozalski Marcin
Published: August 2020

We have shown previously that platelet activity can be lowered through the simultaneous inhibition of P2Y12 receptor and activation of adenosine receptors (AR). This work explores this concept by testing the antiplatelet potential of nine AR agonists in combination with P2Y12 receptor antagonists—cangrelor and prasugrel metabolite. A panel of in vitro methods was used to assess platelet viability, P-selectin expression, GPIIb-IIIa activation, fibrinogen binding, calcium ion mobilization, VASP-P level, and cAMP formation, utilizing whole blood or isolated platelets from healthy volunteers. The AR agonists demonstrated anti-platelet effects, but stimulated signaling pathways to varying degrees. AR agonists and P2Y12 antagonists reduced expression of both P-selectin and the activated form of GPIIb-IIIa on platelets; however, the combined systems (AR agonist + P2Y12 antagonist) demonstrated stronger effects. The antiplatelet effects of AR when combined with P2Y12 were more pronounced with regard to exogenous fibrinogen binding and calcium mobilization. The cAMP levels in both resting and ADPactivated platelets were increased by AR agonist treatment, and more so when combined with P2Y12 inhibitor. In conclusion, as AR agonists are fast-acting compounds, the methods detecting early activation events are more suitable for assessing their antiplatelet action. The exogenous fibrinogen binding, calcium mobilisation and cAMP level turned out to be sensitive markers for detecting the inhibition caused by AR agonists alone or in combination with P2Y12 receptor antagonists.
Assessment of Intracellular Delivery Potential of Novel Sustainable Poly(δ-decalactone)-Based Micelles
Authors: Bansal Kuldeep Kumar , Özliseli Ezgi , Saraogi Gaurav Kumar , Rosenholm Jessica M.
Published: August 2020

Biodegradable polymers from renewable resources have attracted much attention in recent years within the biomedical field. Lately, poly(δ-decalactone) based copolymer micelles have emerged as a potential drug delivery carrier material as a sustainable alternative to fossil-based polymers. However, their intracellular drug delivery potential is not yet investigated and therefore, in this work, we report on the synthesis and cellular uptake efficiency of poly(δ-decalactone) based micelles with or without a targeting ligand. Folic acid was chosen as a model targeting ligand and Rhodamine B as a fluorescent tracer to demonstrate the straightforward functionalisation aspect of copolymers. The synthesis of block copolymers was accomplished by a combination of facile ring-opening polymerisation and click chemistry to retain the structure uniformity. The presence of folic acid on the surface of micelles with diameter ~150 nm upsurge the uptake efficiency by 1.6 fold on folate receptor overexpressing MDA-MB-231 cells indicating the attainment of targeting using ligand functionality. The drug delivery capability of these carriers was ascertained by using docetaxel as a model drug, whereby the in vitro cytotoxicity of the drug was significantly increased after incorporation in micelles 48 h post incubation. We have also investigated the possible endocytosis route of non-targeted micelles and found that caveolae-mediated endocytosis was the preferred route of uptake. This work strengthens the prospect of using novel bio-based poly(δ-decalactone) micelles as efficient multifunctional drug delivery nanocarriers towards medical applications.
Synthesis and Ex Vivo Trans-Corneal Permeation of Penetratin Analogues as Ophthalmic Carriers: Preliminary Results
Authors: Pescina Silvia , Sala Marina , Scala Maria Carmina , Santi Patrizia , Padula Cristina , Campiglia Pietro , Ostacolo Carmine , Nicoli Sara
Published: August 2020

Among enhancing strategies proposed in ocular drug delivery, a rising interest is directed to cell penetrating peptides (CPPs), amino acid short sequences primarily known for their intrinsic ability to cell internalization and, by extension, to cross biological barriers. In fact, CPPs may be considered as carrier for delivering therapeutic agents across biological membranes, including ocular tissues. Several CPPs have been proposed in ophthalmic delivery, and, among them, penetratin (PNT), a 16-amino acids natural peptide, stands out. Therefore, we describe the synthesis via the mimotopic approach of short fluorescently labeled analogues of both PNT and its reversed sequence PNT-R. Their ability to cross ocular membranes was checked ex vivo using freshly explanted porcine cornea. Furthermore, some sequences were studied by circular dichroism. Despite the hydrophilic nature and the relatively high molecular weight (approx. 1.6 kDa), all analogues showed a not negligible trans-corneal diffusion, indicating a partial preservation of penetration activity, even if no sequences reached the noteworthy ability of PNT. It was not possible to find a correlation between structure and corneal penetration ability, and further studies, exploring peptides distribution within corneal layers, for example using imaging techniques, deserve to be performed to figure out a possible difference in intracellular delivery.
Genome-Wide Association Analysis for Tuber Dry Matter and Oxidative Browning in Water Yam (Dioscorea alata L.)
Authors: Gatarira Cobes , Agre Paterne , Matsumoto Ryo , Edemodu Alex , Adetimirin Victor , Bhattacharjee Ranjana , Asiedu Robert , Asfaw Asrat
Published: August 2020

Yam (Dioscorea spp.) is a nutritional and medicinal staple tuber crop grown in the tropics and sub-tropics. Among the food yam species, water yam (Dioscorea alata L.) is the most widely distributed and cultivated species worldwide. Tuber dry matter content (DMC) and oxidative browning (OxB) are important quality attributes that determine cultivar acceptability in water yam. This study used a single nucleotide polymorphism (SNP) assay from a diversity arrays technology (DArT) platform for a genome-wide association study (GWAS) of the two quality traits in a panel of 100 water yam clones grown in three environments. The marker–trait association analysis identified significant SNPs associated with tuber DMC on chromosomes 6 and 19 and with OxB on chromosome 5. The significant SNPs cumulatively explained 45.87 and 12.74% of the total phenotypic variation for the tuber DMC and OxB, respectively. Gene annotation for the significant SNP loci identified important genes associated in the process of the proteolytic modification of carbohydrates in the dry matter accumulation pathway as well as fatty acid β-oxidation in peroxisome for enzymatic oxidation. Additional putative genes were also identified in the peak SNP sites for both tuber dry matter and enzymatic oxidation with unknown functions. The results of this study provide valuable insight for further dissection of the genetic architecture of tuber dry matter and enzymatic oxidation in water yam. They also highlight SNP variants and genes useful for genomics-informed selection decisions in the breeding process for improving food quality traits in water yam.