bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects
Authors: Knaub Katharina , Sartorius Tina , Dharsono Tanita , Wacker Roland , Wilhelm Manfred , Schön Christiane
Published: August 2019

Cannabidiol (CBD), a phytocannabinoid compound of Cannabis sativa, shows limited oral bioavailability due to its lipophilicity and extensive first-pass metabolism. CBD is also known for its high intra- and inter-subject absorption variability in humans. To overcome these limitations a novel self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology incorporating CBD, as Hemp-Extract, was developed (SEDDS-CBD). The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions. As reference formulation, the same Hemp-Extract diluted with medium-chain triglycerides (MCT-CBD) was used. CBD dose was standardized to 25 mg. Pharmacokinetic parameters were analyzed from individual concentration-time curves. Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0–8h/AUC0–24h compared to the reference formulation. Tmax was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h). Subgroup analysis demonstrated a higher bioavailability in women compared to men. This difference was seen for MCT-CBD while SEDDS-CBD mitigated this gender effect. Overall, SEDDS-CBD showed a significant improvement for all determined pharmacokinetic parameters: increased CBD plasma values (Cmax), favorably enhanced bioavailability (AUC) and fast absorption (Tmax). No safety concerns were noted following either administration.
Chlorophyll and Chlorophyll Derivatives Interfere with Multi-Drug Resistant Cancer Cells and Bacteria
Authors: Wang Erjia , Braun Markus Santhosh , Wink Michael
Published: August 2019

Multidrug resistance (MDR) causes challenging tasks in medicine. Human cancer cells, as well as microorganisms, can acquire multiresistance due to the up-regulation of efflux pumps (ABC transporters) and are difficult to treat. Here, we evaluated the effects of chlorophyll, the most abundant pigment on the globe, and its derivative, pheophytin, on cancer cells and methicillin-resistant Staphylococcus aureus (MRSA). We found that both substances have significant reversal effects on multidrug-resistant CEM/ADR5000 cells (RRpheophytin = 3.13, combination index (CI)pheophytin = 0.438; RRchlorophyll = 2.72, CIchlorophyll < 0.407), but not on drug-sensitive CCRF-CEM cells when used in combination with doxorubicin. This indicates that the porphyrins could interact with efflux pumps. Strong synergism was also observed in antimicrobial tests against MRSA when combining ethidium bromide with chlorophyll (FICI = 0.08). As there is a strong need for new drugs in order to reliably treat MDR cells, our research provides potential candidates for further investigation.
Dirhamnolipid Produced by the Pathogenic Fungus Colletotrichum gloeosporioides BWH-1 and Its Herbicidal Activity
Authors: Xu Zhaolin , Shi Mengying , Tian Yongqing , Zhao Pengfei , Niu Yifang , Liao Meide
Published: August 2019

Fungal phytotoxins used as ecofriendly bioherbicides are becoming efficient alternatives to chemical herbicides for sustainable weed management. Previous study found that cultures of the pathogenic fungus Colletotrichum gloeosporioides BWH-1 showed phytotoxic activity. This study further isolated the major phytotoxin from cultures of the strain BWH-1 using bioactivity-guided isolation, by puncturing its host plant for an activity test and analyzing on the HPLC-DAD-3D mode for a purity check. Then, the active and pure phytotoxin was characterized as a dirhamnolipid (Rha-Rha-C10-C10) using the NMR, ESIMS, IR and UV methods. The herbicidal activity of dirhamnolipid was evaluated by the inhibition rate on the primary root length and the fresh plant weight of nine test plants, and the synergistic effect when combining with commercial herbicides. Dirhamnolipid exhibited broad herbicidal activity against eight weed species with IC50 values ranging from 28.91 to 217.71 mg L−1 and no toxicity on Oryza sativa, and the herbicidal activity could be synergistically improved combining dirhamnolipid with commercial herbicides. Thus, dirhamnolipid that originated from C. gloeosporioides BWH-1 displayed the potential to be used as a bioherbicide alone, or as an adjuvant added into commercial herbicides, leading to a decrease in herbicides concentration and increased control efficiency.
Exopolysaccharide Produced by Lactobacillus paracasei IJH-SONE68 Prevents and Improves the Picryl Chloride-Induced Contact Dermatitis
Authors: Noda Masafumi , Sultana Nasrin , Hayashi Ikue , Fukamachi Mitsuhiro , Sugiyama Masanori
Published: August 2019

Allergic disease is one of the most important and common health problems worldwide. We have previously demonstrated that a fig leaf-derived lactic acid bacterium Lactobacillus (Lb.) paracasei IJH-SONE68 produces a novel exopolysaccharide (EPS). Furthermore, we have shown that the EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.36) promoting inflammatory reactions. To evaluate the anti-allergy and anti-inflammatory effects of the EPS, in the present study, we employed the picryl-chloride-induced delayed-type (type IV) allergy model mice, which is used to evaluate the contact dermatitis. Oral administration of the EPS was observed to reduce the ear swelling in the model mice. We also observed that the overexpression of ear interleukin-4 (T helper (Th) 2 cytokine) mRNA and the increase in serum immunoglobulin E (IgE) are repressed. However, the expression of interferon-γ (Th1 cytokine) was not accelerated in all of the allergen-challenged model mice. The improvement may be responsible for the Th2 downregulation rather than the Th1 upregulation. In addition, the symptom of immediate-type (type I) allergy model mice was improved by oral administration of the IJH-SONE68 cell (data not shown). We can conclude that the IJH-SONE68-derived EPS is useful to improve the type I and IV allergies including atopic dermatitis.
SYSU-6, A New 2-D Aluminophosphate Zeolite Layer Precursor
Authors: Qiu Jiang-Zhen , Wang Long-Fei , Jiang Jiuxing
Published: August 2019

Two-dimensional aluminophosphate is an important precursor of phosphate-based zeolites; a new Sun Yat-sen University No. 6 (SYSU-6) with |Hada|2[Al2(HPO4)(PO4)2] has been synthesized in the hydrothermal synthesis with organic structure-directing agent (OSDA) of N,N,3,5-tetramethyladamantan-1-amine. In this paper, SYSU-6 is characterized by single-crystal/powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray analysis, transmission electron microscopy, infrared and UV Raman spectroscopy, solid-state 27Al, 31P and 13C magic angle spinning (MAS) NMR spectra, and elemental analysis. The single-crystal X-ray diffraction structure indicates that SYSU-6 crystallized in the space group P21/n, with a = 8.4119(3), b = 36.9876(12), c = 12.5674(3), α = 90°, β = 108.6770(10)°, γ = 90°, V = 3704.3(2) Å3, Z = 4, R = 5.12%, for 8515 observed data (I > 2σ(I)). The structure has a new 4,12-ring layer framework topology linked by alternating AlO4 and PO4 tetrahedra. The organic molecules reside between the layers and are hydrogen-bonded to the inorganic framework. The new type of layer provides a greater opportunity to construct zeolite with novel topology.
Special Issue: “Smart and Functional Polymers”
Authors: Feng Xiangru , Li Mingqiang , Li Yang , Ding Jianxun
Published: August 2019

Polymerization provides an efficient strategy for synthesizing macromolecules with versatile functionality [...]
Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates
Authors: Pethő Lilla , Mező Gábor , Schlosser Gitta
Published: August 2019

Peptide-based small molecule drug conjugates for targeted tumor therapy are currently in the focus of intensive research. Anthracyclines, like daunomycin, are commonly used anticancer drug molecules and are also often applied in peptide-drug conjugates. However, lability of the O-glycosidic bond during electrospray ionization mass spectrometric analysis hinders the analytical characterization of the constructs. “Overprotonation” can occur if daunomycin is linked to positively charged peptide carriers, like tuftsin derivatives. In these molecules, the high number of positive charges enhances the in-source fragmentation significantly, leading to complex mass spectra composed of mainly fragment ions. Therefore, we investigated different novel tuftsin-daunomycin conjugates to find an appropriate condition for mass spectrometric detection. Our results showed that shifting the charge states to lower charges helped to keep ions intact. In this way, a clear spectrum could be obtained containing intact protonated molecules only. Shifting of the protonation states to lower charges could be achieved with the use of appropriate neutral volatile buffers and with tuning the ion source parameters.
Molecular Imaging Probes Based on Matrix Metalloproteinase Inhibitors (MMPIs)
Authors: Rangasamy Loganathan , Di Geronimo Bruno , Ortín Irene , Coderch Claire , Zapico José María , Ramos Ana , de Pascual-Teresa Beatriz
Published: August 2019

Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases which are secreted or anchored in the cell membrane and are capable of degrading the multiple components of the extracellular matrix (ECM). MMPs are frequently overexpressed or highly activated in numerous human diseases. Owing to the important role of MMPs in human diseases, many MMP inhibitors (MMPIs) have been developed as novel therapeutics, and some of them have entered clinical trials. However, so far, only one MMPI (doxycycline) has been approved by the FDA. Therefore, the evaluation of the activity of a specific subset of MMPs in human diseases using clinically relevant imaging techniques would be a powerful tool for the early diagnosis and assessment of the efficacy of therapy. In recent years, numerous MMPIs labeled imaging agents have emerged. This article begins by providing an overview of the MMP subfamily and its structure and function. The latest advances in the design of subtype selective MMPIs and their biological evaluation are then summarized. Subsequently, the potential use of MMPI-labeled diagnostic agents in clinical imaging techniques are discussed, including positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging (OI). Finally, this article concludes with future perspectives and clinical utility.
Assessment of Antifouling Potential of Novel Transparent Sol Gel Coatings for Application in the Marine Environment
Authors: Richards Chloe , Briciu-Burghina Ciprian , Jacobs Matthew R. , Barrett Alan , Regan Fiona
Published: August 2019

In recent years, there has become a growing need for the development of antifouling technology for application in the marine environment. The accumulation of large quantities of biomass on these surfaces cause substantial economic burdens within the marine industry, or adversely impact the performance of sensor technologies. Here, we present a study of transparent coatings with potential for applications on sensors or devices with optical windows. The focus of the study is on the abundance and diversity of biofouling organisms that accumulate on glass panels coated with novel transparent or opaque organically modified silicate (ORMOSIL) coatings. The diatom assessment was used to determine the effectiveness of the coatings against biofouling. Test panels were deployed in a marine environment in Galway Bay for durations of nine and thirteen months to examine differences in biofilm formation in both microfouling and macrofouling conditions. The most effective coating is one which consists of precursor, tetraethyl orthosilicate (HC006) that has a water contact angle > 100, without significant roughness (43.52 nm). However, improved roughness and wettability of a second coating, diethoxydimethylsilane (DMDEOS), showed real promise in relation to macrofouling reduction.
Enhancement of Volatile Fatty Acids Production from Food Waste by Mature Compost Addition
Authors: Cheah Yen-Keong , Dosta Joan , Mata-Álvarez Joan
Published: August 2019

Food waste (FW) collected from a university canteen was treated in acidogenic fermenters to produce volatile fatty acids (VFA) under biological pretreatment with mature compost. Batch assays working at pH 6 revealed an increment of 9.0%, 7.9%, and 4.1% (on COD basis) of VFA concentration when adding 2.5%, 3.5%, and 4.5% w/w of mature compost, respectively, even though the volatile solids (VS) concentration of food waste was lower in the tests with increasing doses of mature compost. For batch tests at pH 7, this VFA generation improvement was lower, even though enhanced COD solubilization was recorded. Operating in semi-continuous conditions at 35 °C, pH of 6, and hydraulic retention time (HRT) of 3.5 days, the addition of 2.5% w/w of mature compost led to a VFA concentration up to 51.2 ± 12.3% more (on VS basis) when compared to a reference reactor without compost addition. Moreover, the percentage of butyric acid on VS basis in the fermentation broth working at a pH of 6 increased from up to 12.2 ± 1.9% (0% compost addition) to up to 23.5 ± 2.7% (2.5% compost addition). The VFA production was not improved when a higher percentage of mature compost was used (3.5% instead of 2.5% w/w), and it slightly decreased when mature compost addition was lowered to 1.5% w/w. When working at a pH of 7 in the semi-continuous fermenters with the addition of 2.5% w/w mature compost at an HRT of 3.5 days, an improvement of 79% and 104% of the VFA concentration (on VS basis) were recorded as compared to fermenters working at a pH of 6 with 2.5% and 0% w/w of mature compost addition, respectively. At a pH of 7, higher production of propionic and valeric acids was found with respect to the reactor working at a pH of 6. The effect of pH on VFA generation was estimated to have greater contribution than that of only biological pretreatment using mature compost. At a pH of 7, the VFA yield was higher for the fermenter working with 2.5% w/w mature compost but at a pH of 7 and HRT of 5 days, the effect of mature compost on VFA production improvement was lower than that obtained at a pH of 6. Moreover, higher solubilization in terms of soluble chemical oxygen demand and total ammonium was detected when biological pretreatment using mature compost was applied at both a pH of 6 and a pH of 7, which indicates enhanced hydrolysis in both conditions.
Replacement of l-Amino Acids by d-Amino Acids in the Antimicrobial Peptide Ranalexin and Its Consequences for Antimicrobial Activity and Biodistribution
Authors: Domhan Cornelius , Uhl Philipp , Kleist Christian , Zimmermann Stefan , Umstätter Florian , Leotta Karin , Mier Walter , Wink Michael
Published: August 2019

Infections caused by multidrug-resistant bacteria are a global emerging problem. New antibiotics that rely on innovative modes of action are urgently needed. Ranalexin is a potent antimicrobial peptide (AMP) produced in the skin of the American bullfrog Rana catesbeiana. Despite strong antimicrobial activity against Gram-positive bacteria, ranalexin shows disadvantages such as poor pharmacokinetics. To tackle these problems, a ranalexin derivative consisting exclusively of d-amino acids (named danalexin) was synthesized and compared to the original ranalexin for its antimicrobial potential and its biodistribution properties in a rat model. Danalexin showed improved biodistribution with an extended retention in the organisms of Wistar rats when compared to ranalexin. While ranalexin is rapidly cleared from the body, danalexin is retained primarily in the kidneys. Remarkably, both peptides showed strong antimicrobial activity against Gram-positive bacteria and Gram-negative bacteria of the genus Acinetobacter with minimum inhibitory concentrations (MICs) between 4 and 16 mg/L (1.9–7.6 µM). Moreover, both peptides showed lower antimicrobial activities with MICs ≥32 mg/L (≥15.2 µM) against further Gram-negative bacteria. The preservation of antimicrobial activity proves that the configuration of the amino acids does not affect the anticipated mechanism of action, namely pore formation.
The Effect of Substitution Pattern on Binding Ability in Regioisomeric Ion Pair Receptors Based on an Aminobenzoic Platform
Authors: Jagleniec Damian , Ziach Krzysztof , Dąbrowa Kajetan , Romański Jan
Published: August 2019

A series of ditopic ion pair receptors equipped with 4-nitrophenylurea and 1-aza-18-crown-6-ether linked by ortho-(1), meta-(2), and para-(3) substituted benzoic acid were readily synthesized in three steps from commercially available materials. The binding properties of these regioisomeric receptors were determined using UV-vis and 1H NMR spectroscopy in MeCN and in the solid state by single-crystal X-ray diffraction crystallography. The solution studies revealed that, apart from carboxylates, all the anions tested formed stronger complexes in the presence of sodium cations. Receptors 2 and 3 were found to interact with ion pairs with remarkably higher affinity than ortho-substituted 1. 1H NMR titration experiments showed that both urea NH protons interacted with anions with comparable strength in the case of receptors 2 and 3, but only one of the NHs was effective in anion binding in the case of receptor 1. X-ray analysis of the crystal structure of receptor 1 and 1·NaPF6 complex showed that binding was hampered due to the formation of an intramolecular hydrogen bond. Analysis of the crystal structures of 2·NaBr and 3·NaBr complexes revealed that proper mutual orientation of binding domains was responsible for the improved binding of the sodium salts.
Optimization of Ultrasonic-Assisted Extraction and Purification of Zeaxanthin and Lutein in Corn Gluten Meal
Authors: Wang Litao , Lu Weihang , Li Jiali , Hu Jinxia , Ding Ruifang , Lv Mei , Wang Qibao
Published: August 2019

Zeaxanthin and lutein have a wide range of pharmacological applications. In this study, we conducted systematic experimental research to optimize antioxidant extraction based on detection, extraction, process amplification, and purification. An ultrasonic-assisted method was used to extract zeaxanthin and lutein with high efficiency from corn gluten meal. Firstly, the effects of solid-liquid ratio, extraction temperature, and ultrasonic extraction time on the extraction of zeaxanthin were investigated in single-factor experiments. The optimization extraction parameters of zeaxanthin and lutein with ethanol solvent were obtained using the response surface methodology (RSM) as follows: liquid–solid ratio of 7.9:1, extraction temperature of 56 °C, and extraction time of 45 min. The total content of zeaxanthin and lutein was 0.501%. The optimum extraction experimental parameters were verified by process amplification, and we confirmed that the parameters of the extraction process optimized using the RSM design are reliable and precise. Zeaxanthin and lutein from crude extract of corn gluten were separated and purified using silica gel column chromatography with the purity of zeaxanthin increasing from 0.28% to 31.5% (about 110 times) and lutein from 0.25% to 16.3% (about 65 times), which could be used for large-scale industrial production of carotenoids.
Facile Formation of Anatase/Rutile TiO2 Nanocomposites with Enhanced Photocatalytic Activity
Authors: He Jing , Du Yi-en , Bai Yang , An Jing , Cai Xuemei , Chen Yongqiang , Wang Pengfei , Yang Xiaojing , Feng Qi
Published: August 2019

Anatase/rutile mixed-phase TiO2 nanoparticles were synthesized through a simple sol-gel route with further calcination using inexpensive titanium tetrachloride as a titanium source, which effectively reduces the production cost. The structural and optical properties of the prepared materials were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), and UV-vis adsorption. The specific surface area was also analyzed by Brunauer–Emmett–Teller (BET) method. The anatase/rutile mixed-phase TiO2 nanocomposites containing of rod-like, cuboid, and some irregularly shaped anatase nanoparticles (exposed {101} facets) with sizes ranging from tens to more than 100 nanometers, and rod-like rutile nanoparticles (exposed {110} facets) with sizes ranging from tens to more than 100 nanometers. The photocatalytic activities of the obtained anatase/rutile mixed-phase TiO2 nanoparticles were investigated and compared by evaluating the degradation of hazardous dye methylene blue (MB) under ultraviolet light illumination. Compared to the commercial Degussa P25-TiO2, the mixed-phase TiO2 nanocomposites show better photocatalytic activity, which can be attributed to the optimal anatase to rutile ratio and the specific exposed crystal surface on the surface. The anatase/rutile TiO2 nanocomposites obtained at pH 1.0 (pH1.0-TiO2) show the best photocatalytic activity, which can be attributed to the optimal heterojunction structure, the smaller average particle size, and the presence of a specific exposed crystal surface. The enhanced photocatalytic activity makes the prepared anatase/rutile TiO2 photocatalysts a potential candidate in the removal of the organic dyes from colored wastewater.
Bee Venom: Overview of Main Compounds and Bioactivities for Therapeutic Interests
Authors: Wehbe Rim , Frangieh Jacinthe , Rima Mohamad , El Obeid Dany , Sabatier Jean-Marc , Fajloun Ziad
Published: August 2019

Apitherapy is an alternate therapy that relies on the usage of honeybee products, most importantly bee venom for the treatment of many human diseases. The venom can be introduced into the human body by manual injection or by direct bee stings. Bee venom contains several active molecules such as peptides and enzymes that have advantageous potential in treating inflammation and central nervous system diseases, such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. Moreover, bee venom has shown promising benefits against different types of cancer as well as anti-viral activity, even against the challenging human immunodeficiency virus (HIV). Many studies described biological activities of bee venom components and launched preclinical trials to improve the potential use of apitoxin and its constituents as the next generation of drugs. The aim of this review is to summarize the main compounds of bee venom, their primary biological properties, mechanisms of action, and their therapeutic values in alternative therapy strategies.
Drug-Target Interaction Prediction Based on Drug Fingerprint Information and Protein Sequence
Authors: Li Yang , Huang Yu-An , You Zhu-Hong , Li Li-Ping , Wang Zheng
Published: August 2019

The identification of drug-target interactions (DTIs) is a critical step in drug development. Experimental methods that are based on clinical trials to discover DTIs are time-consuming, expensive, and challenging. Therefore, as complementary to it, developing new computational methods for predicting novel DTI is of great significance with regards to saving cost and shortening the development period. In this paper, we present a novel computational model for predicting DTIs, which uses the sequence information of proteins and a rotation forest classifier. Specifically, all of the target protein sequences are first converted to a position-specific scoring matrix (PSSM) to retain evolutionary information. We then use local phase quantization (LPQ) descriptors to extract evolutionary information in the PSSM. On the other hand, substructure fingerprint information is utilized to extract the features of the drug. We finally combine the features of drugs and protein together to represent features of each drug-target pair and use a rotation forest classifier to calculate the scores of interaction possibility, for a global DTI prediction. The experimental results indicate that the proposed model is effective, achieving average accuracies of 89.15%, 86.01%, 82.20%, and 71.67% on four datasets (i.e., enzyme, ion channel, G protein-coupled receptors (GPCR), and nuclear receptor), respectively. In addition, we compared the prediction performance of the rotation forest classifier with another popular classifier, support vector machine, on the same dataset. Several types of methods previously proposed are also implemented on the same datasets for performance comparison. The comparison results demonstrate the superiority of the proposed method to the others. We anticipate that the proposed method can be used as an effective tool for predicting drug-target interactions on a large scale, given the information of protein sequences and drug fingerprints.
Understanding Conformational Preferences of Atropisomeric Hydrazides and Its Influence on Excited State Transformations in Crystalline Media
Authors: Iyer Akila , Ugrinov Angel , Sivaguru J.
Published: August 2019

Hydrazides derivatives were evaluated to understand the role of N–N bond in dictating the outcome of photoreactions in the solid state.
Protective Effects Induced by Two Polyphenolic Liquid Complexes from Olive (Olea europaea, mainly Cultivar Coratina) Pressing Juice in Rat Isolated Tissues Challenged with LPS
Authors: Recinella Lucia , Chiavaroli Annalisa , Orlando Giustino , Menghini Luigi , Ferrante Claudio , Di Cesare Mannelli Lorenzo , Ghelardini Carla , Brunetti Luigi , Leone Sheila
Published: August 2019

MOMAST(®) HY100 and MOMAST(®) HP30 are polyphenolic liquid complexes from olive pressing juice with a total polyphenolic content of 100 g/kg (at least 50% as hydroxytyrosol) and 36 g/kg (at least 30% as hydroxytyrosol), respectively. We investigated the potential protective role of MOMAST(®) HY100 and MOMAST(®) HP30 on isolated rat colon, liver, heart, and prefrontal cortex specimens treated with Escherichia coli lipopolysaccharide (LPS), a validated ex vivo model of inflammation, by measuring the production of prostaglandin (PG)E2, 8-iso-PGF2α, lactate dehydrogenase (LDH), as well as cyclooxygenase (COX)-2, tumor necrosis factor α (TNFα), and inducible nitric oxide synthase (iNOS) mRNA levels. MOMAST(®) HY100 decreased LPS-stimulated PGE2 and LDH levels in all tested tissues. Following treatment with MOMAST(®) HY100, we found a significant reduction in iNOS levels in prefrontal cortex and heart specimens, COX-2 and TNFα mRNA levels in heart specimens, and 8-iso-PGF2α levels in liver specimens. On the other hand, MOMAST(®) HP30 was found to blunt COX-2, TNFα, and iNOS mRNA levels, as well as 8-iso-PGF2α in cortex, liver, and colon specimens. MOMAST(®) HP30 was also found to decrease PGE2 levels in liver specimens, while it decreased iNOS mRNA, LDH, and 8-iso-PGF2α levels in heart specimens. Both MOMAST(®) HY100 and MOMAST(®) HP30 exhibited protective effects on multiple inflammatory and oxidative stress pathways.
Comparative Analysis of Phytochemical Composition of Gamma-Irradiated Mutant Cultivars of Chrysanthemum morifolium
Authors: Ryu Jaihyunk , Nam Bomi , Kim Bo-Ram , Kim Sang Hoon , Jo Yeong Deuk , Ahn Joon-Woo , Kim Jin-Baek , Jin Chang Hyun , Han Ah-Reum
Published: August 2019

The flowers of chrysanthemum species are used as a herbal tea and in traditional medicine. In addition, members of the genus have been selected to develop horticultural cultivars of diverse floral colors and capitulum forms. In this research, we investigated the phytochemical composition of eight gamma-irradiation mutant cultivars of Chrysanthemum morifolium and their original cultivars. The mutant chrysanthemum cultivars were generated by treatment with various doses of 60Co gamma irradiation of stem cuttings of three commercial chrysanthemum cultivars as follows: ‘ARTI-Dark Chocolate’ (50Gy), ‘ARTI-Purple Lady’ (30 Gy), and ‘ARTI-Yellow Star’ (50 Gy) derived from ‘Noble Wine’; ‘ARTI-Red Star’ (50 Gy) and ‘ARTI-Rising Sun’ (30 Gy) from ‘Pinky’; ‘ARTI-Purple’ (40 Gy) and ‘ARTI-Queen’ (30 Gy) from ‘Argus’; and ‘ARTI-Rollypop’ (70 Gy) from ‘Plaisir d’amour’. Quantitative analysis of flavonoids, phenolic acids, anthocyanins, and carotenoids in the flowers of the 12 chrysanthemum cultivars was performed using high performance liquid chromatography-diode array detector-electrospray ionization mass spectrometry (HPLC-DAD-ESIMS). Essential oils from the flowers of these cultivars were analyzed by gas chromatography–mass spectrometry (GC-MS). The mutant cultivars, ‘ARTI-Dark Chocolate’, ‘ARTI-Purple Lady’, ‘ARTI-Purple’, and ‘ARTI-Queen’ showed higher total amounts of flavonoid and phenolic acid compared with those of the respective original cultivars. The mutant cultivars, ‘ARTI-Dark Chocolate’, ‘ARTI-Purple Lady’ and ‘ARTI-Purple’, which produce purple to pink petals, contained more than two-times higher amounts of anthocyanins compared with those of their original cultivars. Of the mutant cultivars, ‘ARTI-Yellow Star’ in which petal color was changed to yellow, showed the greatest accumulation of carotenoids. Ninety-nine volatile compounds were detected, of which hydrocarbons and terpenoids were abundant in all cultivars analyzed. This is the first report that demonstrated the phytochemical analysis of novel chrysanthemum cultivars derived from C. morifolium hydrid using HPLC-DAD-ESIMS and GC-MS. These findings suggest that the selected mutant chrysanthemum cultivars show potential as a functional source of phytochemicals associated with the abundance of health-beneficial components, as well as good source for horticulture and pigment industries.
Hydrogels Based on Schiff Base Linkages for Biomedical Applications
Authors: Xu Junpeng , Liu Yi , Hsu Shan-hui
Published: August 2019

Schiff base, an important family of reaction in click chemistry, has received significant attention in the formation of self-healing hydrogels in recent years. Schiff base reversibly reacts even in mild conditions, which allows hydrogels with self-healing ability to recover their structures and functions after damages. Moreover, pH-sensitivity of the Schiff base offers the hydrogels response to biologically relevant stimuli. Different types of Schiff base can provide the hydrogels with tunable mechanical properties and chemical stabilities. In this review, we summarized the design and preparation of hydrogels based on various types of Schiff base linkages, as well as the biomedical applications of hydrogels in drug delivery, tissue regeneration, wound healing, tissue adhesives, bioprinting, and biosensors.
High-Power GaN-Based Vertical Light-Emitting Diodes on 4-Inch Silicon Substrate
Authors: Zhao Qiang , Miao Jiahao , Zhou Shengjun , Gui Chengqun , Tang Bin , Liu Mengling , Wan Hui , Hu Jinfeng
Published: August 2019

We demonstrate high-power GaN-based vertical light-emitting diodes (LEDs) (VLEDs) on a 4-inch silicon substrate and flip-chip LEDs on a sapphire substrate. The GaN-based VLEDs were transferred onto the silicon substrate by using the Au–In eutectic bonding technique in combination with the laser lift-off (LLO) process. The silicon substrate with high thermal conductivity can provide a satisfactory path for heat dissipation of VLEDs. The nitrogen polar n-GaN surface was textured by KOH solution, which not only improved light extract efficiency (LEE) but also broke down Fabry–Pérot interference in VLEDs. As a result, a near Lambertian emission pattern was obtained in a VLED. To improve current spreading, the ring-shaped n-electrode was uniformly distributed over the entire VLED. Our combined numerical and experimental results revealed that the VLED exhibited superior heat dissipation and current spreading performance over a flip-chip LED (FCLED). As a result, under 350 mA injection current, the forward voltage of the VLED was 0.36 V lower than that of the FCLED, while the light output power (LOP) of the VLED was 3.7% higher than that of the FCLED. The LOP of the FCLED saturated at 1280 mA, but the light output saturation did not appear in the VLED.
The Role of Fluorinated IL as an Interfacial Agent in P(VDF-CTFE)/Graphene Composite Films
Authors: Yang Jing , Pruvost Sébastien , Livi Sébastien , Duchet-Rumeau Jannick
Published: August 2019

The incorporation of graphene into a polymer matrix can endow composites with extended functions. However, it is difficult to well disperse pristine graphene into a polymer matrix in order to obtain polymer nanocomposites due to the lack of functional groups on the surface for bonding with a polymer matrix. Herein, we investigated the role of fluorinated ionic liquid (IL) as a new interfacial agent in poly(vinylidene fluoride-co-chlorotrifluoroethylene) (P(VDF-CTFE))/graphene composite films. First, a task-specific IL, perfluorooctyltriphenylphosphonium iodide (IL-C8F13), was synthesized and adsorbed on the surface of graphene oxide (GO) and reduced graphene oxide (rGO) for making functional nanofillers which were capable of being incorporated into the P(VDF-CTFE) matrix. The cation structure of IL combined three phenyls (potential π–π interactions with graphene) and a short fluorinated chain (enhanced miscibility with fluorinated matrix via dipolar interactions) to make a compatible graphene filler and P(VDF-CTFE) matrix at the interface among them. Second, two series of P(VDF-CTFE)/GO-IL and P(VDF-CTFE)/rGO-IL composites with different loading contents were prepared with the goal of providing an understanding of the mechanism of interfacial interactions. This paper investigated the difference in the interaction model between GO with IL and rGO with IL. Subsequently, the interfacial effect of IL on the properties of P(VDF-CTFE)/graphene composites, such as crystallization, chain segmental relaxation behavior, dispersion, and the final dielectric properties will be further studied.
Effects of Lactobacillus plantarum and Lactobacillus paracasei on the Peripheral Immune Response in Children with Celiac Disease Autoimmunity: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Håkansson Åsa , Andrén Aronsson Carin , Brundin Charlotte , Oscarsson Elin , Molin Göran , Agardh Daniel
Published: August 2019

Two Lactobacillus strains have proven anti-inflammatory properties by reducing pro-inflammatory responses to antigens. This randomized double-blind placebo-controlled trial tested the hypothesis that L. plantarum HEAL9 and L. paracasei 8700:2 suppress ongoing celiac disease autoimmunity in genetically at risk children on a gluten-containing diet in a longitudinally screening study for celiac disease. Seventy-eight children with celiac disease autoimmunity participated of whom 40 received 1010 CFU/day of L. plantarum HEAL9 and L. paracasei 8700:2 (probiotic group) and 38 children maltodextrin (placebo group) for six months. Blood samples were drawn at zero, three and six months and phenotyping of peripheral blood lymphocytes and IgA and IgG autoantibodies against tissue transglutaminase (tTG) were measured. In the placebo group, naïve CD45RA+ Th cells decreased (p = 0.002) whereas effector and memory CD45RO+ Th cells increased (p = 0.003). In contrast, populations of cells expressing CD4+CD25highCD45RO+CCR4+ increased in the placebo group (p = 0.001). Changes between the groups were observed for NK cells (p = 0.038) and NKT cells (p = 0.008). Median levels of IgA-tTG decreased more significantly over time in the probiotic (p = 0.013) than in the placebo (p = 0.043) group whereas the opposite was true for IgG-tTG (p = 0.062 respective p = 0.008). In conclusion, daily oral administration of L. plantarum HEAL9 and L. paracasei 8700:2 modulate the peripheral immune response in children with celiac disease autoimmunity.
Effect of Long-Term Omega 3 Polyunsaturated Fatty Acid Supplementation with or without Multidomain Lifestyle Intervention on Muscle Strength in Older Adults: Secondary Analysis of the Multidomain Alzheimer Preventive Trial (MAPT)
Authors: Rolland Yves , Barreto Philipe de Souto , Maltais Mathieu , Guyonnet Sophie , Cantet Christelle , Andrieu Sandrine , Vellas Bruno
Published: August 2019

Background: The benefits of long-term omega 3 polyunsaturated fatty acid (ω3-PUFA) supplementation on muscle strength in older adults remains to be investigated. Objectives: We assessed the effect of ω3-PUFA supplementation and a multidomain (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on muscle strength. We also hypothesized that ω3-PUFA supplementation resulted in additional benefit in participants with a low docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) erythrocyte level at baseline and high adherence to the multidomain intervention sessions. Design: We performed secondary analyses of the Multidomain Alzheimer Preventive Trial (MAPT), a 3-year, multicenter, randomized, placebo-controlled trial with four parallel groups. Participants were non-demented, aged 70 years or older. They were recruited in 13 memory clinics in France and Monaco between 30 May 2008 and 24 February 2011. Participants were randomly assigned to either ω3-PUFA alone (two capsules a day providing a total daily dose of 800 mg DHA and 225 mg EPA), ω3-PUFA plus the multidomain intervention (43 group sessions integrating advice for physical activity (PA), and nutrition, cognitive training, and three preventive consultations), the multidomain intervention plus placebo, or placebo alone. Our primary outcome was the change from baseline to 36 months of the muscle strength assessed with the repeated chair stand test and handgrip strength. Results: A total of 1680 participants (75.34 years ± 4.42) were randomized. In the modified intention-to-treat population (n = 1679), no significant differences at 3-year follow-up were observed in the repeated chair stand test score between any of the three intervention groups and the placebo group. The between-group differences compared with placebo were −0.05388 (−0.6800 to 0.5723; Standard Error, SE = 0.3192; p = 0.8660) for the ω3-PUFA group, −0.3936 (−1.0217 to 0.2345; SE = 0.3180; p = 0.2192) for the multidomain intervention plus placebo group, and −0.6017 (−1.2255 to 0.02222; SE = 0.2092; p = 0.3202) for the combined intervention group. No significant effect was also found for the handgrip strength. Sensitivity analyses performed among participants with low (DHA+EPA) erythrocyte level at baseline (first quartile vs. others) or highly adherent participants (≥75% of the multidomain intervention sessions) revealed similar results. Conclusion: Low dose ω3-PUFA supplementation, either alone or in combination with a multidomain lifestyle intervention comprising physical activity counselling, had no significant effects on muscle strength over 3 years in elderly people.
Consumers’ Perceptions of Five Front-of-Package Nutrition Labels: An Experimental Study Across 12 Countries
Authors: Talati Zenobia , Egnell Manon , Hercberg Serge , Julia Chantal , Pettigrew Simone
Published: August 2019

Consumers’ perceptions of five front-of-pack nutrition label formats (health star rating (HSR), multiple traffic lights (MTL), Nutri-Score, reference intakes (RI) and warning label) were assessed across 12 countries (Argentina, Australia, Bulgaria, Canada, Denmark, France, Germany, Mexico, Singapore, Spain, the UK and the USA). Perceptions assessed included liking, trust, comprehensibility, salience and desire for the label to be mandatory. A sample of 12,015 respondents completed an online survey in which they rated one of the five (randomly allocated) front-of-pack labels (FoPLs) along the perception dimensions described above. Respondents viewing the MTL provided the most favourable ratings. Perceptions of the other FoPLs were mixed or neutral. No meaningful or consistent patterns were observed in the interactions between country and FoPL type, indicating that culture was not a strong predictor of general perceptions. The overall ranking of the FoPLs differed somewhat from previous research assessing their objective performance in terms of enhancing understanding of product healthiness, in which the Nutri-Score was the clear front-runner. Respondents showed a strong preference for mandatory labelling, regardless of label condition, which is consistent with past research showing that the application of labels across all products leads to healthier choices.
Association between Dietary Isoflavone Intake and Ulcerative Colitis Symptoms in Polish Caucasian Individuals
Authors: Skolmowska Dominika , Głąbska Dominika , Guzek Dominika , Lech Gustaw
Published: August 2019

Currently there are contradictory observations regarding the associations between the isoflavone intake and inflammatory bowel disease in terms of its prevention and treatment, and this may be attributed to the diversity of applied doses and influence of various isoflavones. The aim of the presented cross-sectional study is to analyze the association between intake of various isoflavones (daidzein, genistein, glicytein and total isoflavones) and ulcerative colitis symptoms (fecal blood, mucus and pus) in Polish Caucasian individuals in confirmed remission. Assessment of diet was based on self-reported data obtained from patients’ three-day dietary records and their individual assessments of symptoms. A total of 56 Caucasian patients with ulcerative colitis in confirmed remission were recruited for the study (37 females and 19 males, aged 18–80). For individuals with no fecal mucus observed, higher daidzein (p = 0.035, 122 vs. 19 µg) and total isoflavone intakes (p = 0.034, 302.2 vs. 123.7 µg) were observed in comparison with individuals not declaring this symptom, while for daidzein it was confirmed for the component density of their diets. The opposite association was stated for fecal pus, as for individuals with a lack of this symptom, lower daidzein intake was stated in comparison with individuals declaring this symptom (p = 0.049, 103.3 vs. 206.7 µg), but it was not confirmed for the component density of the diets. It was stated that the high intake of isoflavones by Caucasian individuals, as in a western diet, may influence the symptoms of ulcerative colitis, with the strongest influence by daidzein. Taking this into account, isoflavones may be included into the diets of ulcerative colitis patients in remission if well-tolerated, but there is a need for further study.
GDM and Nutrition—Answered and Unanswered Questions—There’s More Work to Do!
Authors: Simmons David
Published: August 2019

Gestational Diabetes Mellitus (GDM) is the commonest medical pregnancy complication, and a growing problem around the world as the obesity epidemic continues. Ways to prevent GDM are urgently required, the management of GDM still poses many unanswered questions, and the postpartum prevention of the progression of GDM to type 2 diabetes remains a challenge. With GDM, the impact of any intervention on the offspring is always a major concern. Nutritional interventions come to the fore as one of our few levers in reducing the short-term pregnancy risk and long-term cardiometabolic risks to both mother and child. This special issue reports on the relationship between several nutrients and foods and the development and management of GDM, behavioural strategies to enhance lifestyle choices, the issues raised by prior bariatric surgery and ways to screen for GDM. The work identifies further unanswered questions over nutritional strategies to reduce the impact of GDM.
Comparison of 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Rac-Glycerol-Loaded Self-Emulsifying Granule and Solid Self-Nanoemulsifying Drug Delivery System: Powder Property, Dissolution and Oral Bioavailability
Authors: Kim Dong Shik , Kim Jung Suk , Lim Soo-Jeong , Kim Jong Oh , Yong Chul Soon , Choi Han-Gon , Jin Sung Giu
Published: August 2019

The main objective of this study was to compare the powder property, dissolution and bioavailability of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG)-loaded self-emulsifying granule system (SEGS) and solid self-nanoemulsifying drug delivery system (SNEDDS). Various SEGS formulations were prepared, and the effect of surfactant and binder on the drug solubility in them, leading to selecting sodium lauryl sulphate (SLS) and hydroxyl propyl methyl cellulose (HPMC). The SEGS and SNEDDS were prepared with PLAG/SLS/HPMC/calcium silicate/microcrystalline cellulose at the weight ratio of 1:0.25:0.1:0.5:3 employing the fluid bed granulation and spray-drying technique, respectively. Their powder properties were compared in terms of flow ability, emulsion droplet size, scanning electron microscopy, and powder X-ray diffraction. Furthermore, the solubility, dissolution, and oral bioavailability in rats of the SEGS were assessed in comparison with the SNEDDS. The SEGS and SNEDDS enhanced the solubility of the drug approximately 36- and 32-fold as compared with the drug alone; but they had no differences. The crystalline drug may exist in both the calcium silicate and microcrystalline cellulose (MCC) in the SEGS, but only in the calcium silicate in the SNEDDS. The SEGS had considerably improved the flow ability (Hausner ratio, 1.23 vs. 1.07; Carr index, 19.8 vs. 43.5%) and drug dissolution as compared with the SNEDDS. The SEGS and SNEDDS with double peak profiles, unlike the single peak of drug alone, showed a significantly higher plasma concentration and area under the curve (AUC), as compared with drug alone. Although they were not significantly different, the SEGS gave higher AUC than did the SNEDDS, suggesting its enhanced oral bioavailability of PLAG. Thus, the SEGS could be used as a powerful oral dosage form to improve the flow ability and oral bioavailability of PLAG, an oily drug.
In Vitro and In Vivo Test Methods for the Evaluation of Gastroretentive Dosage Forms
Authors: Schneider Felix , Koziolek Mirko , Weitschies Werner
Published: August 2019

More than 50 years ago, the first concepts for gastroretentive drug delivery systems were developed. Despite extensive research in this field, there is no single formulation concept for which reliable gastroretention has been demonstrated under different prandial conditions. Thus, gastroretention remains the holy grail of oral drug delivery. One of the major reasons for the various setbacks in this field is the lack of predictive in vitro and in vivo test methods used during preclinical development. In most cases, human gastrointestinal physiology is not properly considered, which leads to the application of inappropriate in vitro and animal models. Moreover, conditions in the stomach are often not fully understood. Important aspects such as the kinetics of fluid volumes, gastric pH or mechanical stresses have to be considered in a realistic manner, otherwise, the gastroretentive potential as well as drug release of novel formulations cannot be assessed correctly in preclinical studies. This review, therefore, highlights the most important aspects of human gastrointestinal physiology and discusses their potential implications for the evaluation of gastroretentive drug delivery systems.