bluuebunny/crossref_metadata_2025 huggingface dataset:
Realization of Rapid Large-Size 3D Printing Based on Full-Color Powder-Based 3DP Technique
Authors: Chen Guangxue , Wang Xiaochun , Chen Haozhi , Chen Chen
Published: April 2020

The powder-based 3DP (3D printing) technique has developed rapidly in creative and customized industries on account of it’s uniqueness, such as low energy consumption, cheap consumables, and non-existent exhaust emissions. Moreover, it could actualize full-color 3D printing. However, the printing time and size are both in need of upgrade using ready printers, especially for large-size 3D printing objects. Given the above issues, the effects of height and monolayer area on printing time were explored and the quantitative relationship was given in this paper conducted on the specimens with a certain gradient. On this basis, an XYX rotation method was proposed to minimize the printing time. The mechanical tests were conducted with three impregnation types as well as seven printing angles and combined with the characterization of surface structure based on the scanning electron microscope (SEM) digital images to explore the optimum parameters of cutting-bonding frame (CBF) applied to powder-based 3D printing. Then, four adhesives were compared in terms of the width of bonded gap and chromatic aberration. The results revealed that ColorBond impregnated specimens showed excellent mechanical properties which reached maximum when printed at 45° to Z axis, and α-cyanoacrylate is the most suitable adhesive to bond full-color powder-based models. Finally, an operation technological process was summarized to realize the rapid manufacturing of large-size full-color 3D printed objects.
Inhibition of Programmed Death Receptor-1/Programmed Death Ligand-1 Interactions by Ginsenoside Metabolites
Authors: Yim Nam-Hui , Kim Young Soo , Chung Hwan-Suck
Published: April 2020

Evidence suggests that programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) targeted inhibitors act as an immune checkpoint blockade, indicating that these compounds may be useful in cancer immunotherapy by inhibiting the immune response between T-cells and tumors. Previous studies have shown that ginsenosides can regulate the expression of PD-1 and PD-L1 in target diseases; however, it remains unknown whether ginsenosides act as a blockade of PD-1/PD-L1 interactions. In this study, we used competitive ELISA to investigate 12 ginsenosides for their ability to block PD-1/PD-L1 interactions. In addition, we performed a protein–ligand docking simulation and examined the hydrophobic interactions and hydrogen bonds formed at the interfaces between the ginsenosides and PD-L1/PD-1. Eight out of the 12 ginsenosides studied showed inhibition of PD-1/PD-L1 interactions at 35% at the maximum concentration (1 μM). Among them, Rg3 and Compound K (C-K) demonstrated the highest inhibitory effects. Rg3 and C-K were further identified for their interaction efficacy with PD-1/PD-L1, which supported our results demonstrating the blocking activity of these compounds against PD-1/PD-L1 binding interactions. Collectively, our findings suggest that some ginsenosides, including Rg3 and C-K, inhibit PD-1/PD-L1 binding interactions. Therefore, these compounds may prove useful as part of an overall immuno-oncological strategy.
Stability Evaluation of DMT and Harmala Alkaloids in Ayahuasca Tea Samples
Authors: de Oliveira Silveira Gabriela , Guimarães dos Santos Rafael , Rebello Lourenço Felipe , Novak Rossi Giordano , Hallak Jaime , Yonamine Mauricio
Published: April 2020

Ayahuasca tea is a hallucinogenic beverage used for religious purposes in Brazil and many other countries that has therapeutic potential in the treatment of some mental health disorders. In the context of psychedelic research, quantification of the tea’s main alkaloids prior to its administration in animal or human studies is essential. For this reason, this study aims to provide information regarding the stability of the main ayahuasca alkaloids (dimethyltryptamine, DMT; harmine, HRM; tetrahydroharmine, THH; harmaline, HRL) in three different conditions: (1) A year stored in a refrigerator either in plastic or glass containers, (2) seven days at 37 °C to reproduce usual mail transportation, and (3) after three freeze–thaw cycles. Samples were quantified after a dilute-and-shoot procedure using liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). There was no significant degradation of DMT concentration over time in all tested conditions. Harmala alkaloids (THH, HRL, and HRM) showed important variations after long-term and high-temperature storages. Although DMT has proven to be stable in all studied conditions, the harmala alkaloids revealed intense degradation and even concentration increment. This may be caused by degradation, alkaloid inter-conversion, and leaching from tea precipitate material. Therefore, ayahuasca quantification before administration in controlled sets is mandatory.
A Hybrid Nanomaterial Based on Single Walled Carbon Nanotubes Cross-Linked via Axially Substituted Silicon (IV) Phthalocyanine for Chemiresistive Sensors
Authors: Polyakov Maxim , Ivanova Victoria , Klyamer Darya , Köksoy Baybars , Şenocak Ahmet , Demirbaş Erhan , Durmuş Mahmut , Basova Tamara
Published: April 2020

In this work, the novel hybrid nanomaterial SWCNT/SiPc made of single walled carbon nanotubes (SWCNT) cross-linked via axially substituted silicon (IV) phthalocyanine (SiPc) was studied as the active layer of chemiresistive layers for the detection of ammonia and hydrogen. SWCNT/SiPc is the first example of a carbon-based nanomaterial in which an axially substituted phthalocyanine derivative is used as a linker. The prepared hybrid material was characterized by spectroscopic methods, thermogravimetry, scanning and transmission electron microscopies. The layers of the prepared hybrid were tested as sensors toward ammonia and hydrogen by a chemiresistive method at different temperatures and relative humidity as well as in the presence of interfering gases like carbon dioxide, hydrogen sulfide and volatile organic vapors. The hybrid layers exhibited the completely reversible sensor response to both gases at room temperature; the recovery time was 100–200 s for NH3 and 50–120 s in the case of H2 depending on the gas concentrations. At the relative humidity (RH) of 20%, the sensor response was almost the same as that measured at RH 5%, whereas the further increase of RH led to its 2–3 fold decrease. It was demonstrated that the SWCNT/SiPc layers can be successfully used for the detection of both NH3 and H2 in the presence of CO2. On the contrary, H2S was found to be an interfering gas for the NH3 detection.
Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents
Authors: Deda Daiana K. , Iglesias Bernardo A. , Alves Eduardo , Araki Koiti , Garcia Celia R. S.
Published: April 2020

Porphyrins and analogous macrocycles exhibit interesting photochemical, catalytic, and luminescence properties demonstrating high potential in the treatment of several diseases. Among them can be highlighted the possibility of application in photodynamic therapy and antimicrobial/antiparasitic PDT, for example, of malaria parasite. However, the low efficiency generally associated with their low solubility in water and bioavailability have precluded biomedical applications. Nanotechnology can provide efficient strategies to enhance bioavailability and incorporate targeted delivery properties to conventional pharmaceuticals, enhancing the effectiveness and reducing the toxicity, thus improving the adhesion to the treatment. In this way, those limitations can be overcome by using two main strategies: (1) Incorporation of hydrophilic substituents into the macrocycle ring while controlling the interaction with biological systems and (2) by including them in nanocarriers and delivery nanosystems. This review will focus on antiparasitic drugs based on porphyrin derivatives developed according to these two strategies, considering their vast and increasing applications befitting the multiple roles of these compounds in nature.
Mechanical Characterization on Solvent Treated Cellulose Nanofiber Preforms Using Solution Dipping–Hot Press Technique
Authors: Thirunavukarasu Devendran , Shimamura Yoshinobu , Tohgo Keiichiro , Fujii Tomoyuki
Published: April 2020

Nanocomposites films were prepared by impregnating the solvent treated cellulose nanofiber (SCNF) preforms with epoxy resin using a solution dipping–hot press technique. We investigated the effect of SCNF preforms porosity on the amount of impregnated resin and tensile properties of the corresponding nanocomposites films. The porosity of the CNF preforms was successfully controlled using the solvent exchange with varying CNF concentration. The impregnated resin amount increased as the SCNF preforms porosity increased, respectively. Resulting nanocomposite films showed higher mechanical properties than that of the SCNF preforms. The best mechanical properties of composites were found with the combination of 1 wt % SCNF preform and low viscosity epoxy, exhibiting tensile strength and Young’s modulus of 77 MPa and 4.8 GPa, respectively. The composite also showed high fiber volume fraction of more than 60%.
Composition Tuning of Nanostructured Binary Copper Selenides through Rapid Chemical Synthesis and Their Thermoelectric Property Evaluation
Authors: Hamawandi Bejan , Ballikaya Sedat , Råsander Mikael , Halim Joseph , Vinciguerra Lorenzo , Rosén Johanna , Johnsson Mats , S. Toprak Muhammet
Published: April 2020

Reduced energy consumption and environmentally friendly, abundant constituents are gaining more attention for the synthesis of energy materials. A rapid, highly scalable, and process-temperature-sensitive solution synthesis route is demonstrated for the fabrication of thermoelectric (TE) Cu2−xSe. The process relies on readily available precursors and microwave-assisted thermolysis, which is sensitive to reaction conditions; yielding Cu1.8Se at 200 °C and Cu2Se at 250 °C within 6–8 min reaction time. Transmission electron microscopy (TEM) revealed crystalline nature of as-made particles with irregular truncated morphology, which exhibit a high phase purity as identified by X-ray powder diffraction (XRPD) analysis. Temperature-dependent transport properties were characterized via electrical conductivity, Seebeck coefficient, and thermal diffusivity measurements. Subsequent to spark plasma sintering, pure Cu1.8Se exhibited highly compacted and oriented grains that were similar in size in comparison to Cu2Se, which led to its high electrical and low thermal conductivity, reaching a very high power-factor (24 µW/K−2cm−1). Density-of-states (DOS) calculations confirm the observed trends in electronic properties of the material, where Cu-deficient phase exhibits metallic character. The TE figure of merit (ZT) was estimated for the materials, demonstrating an unprecedentedly high ZT at 875 K of 2.1 for Cu1.8Se sample, followed by 1.9 for Cu2Se. Synthetic and processing methods presented in this work enable large-scale production of TE materials and components for niche applications.
Got Mylk? The Emerging Role of Australian Plant-Based Milk Alternatives as A Cow’s Milk Substitute
Authors: Zhang Yianna Y. , Hughes Jaimee , Grafenauer Sara
Published: April 2020

Growing ethical, environmental and health concerns have encouraged demand for novel plant-based milk alternatives, yet it remains nebulous whether these products are nutritionally adequate as cow’s milk replacements. The aim of this study was to conduct a cross-sectional survey of plant-based milk alternatives available in major Australian supermarkets and selected niche food retailers from November 2019 to January 2020 and assess two dietary scenarios (adolescents and older women) where dairy serves were substituted for plant-based alternatives against Australian Estimated Average Requirements (EAR). We collected compositional data from nutrition panels in juxtaposition with derivatives from the Australian Food Composition database, with a total of 115 products, including tree nuts and seeds (n = 48), legumes (n = 27), coconut (n = 10), grains (n = 19) and mixed sources (n = 10). Just over 50% of products were fortified, but only 1/3 contained similar calcium content to cow’s milk. Indiscriminate substitutions might reduce intakes of protein and micronutrients, particularly vitamin A, B2, B12, iodine and zinc, and lead to reductions >50% of the EARs for protein, zinc and calcium in the chosen dietary scenarios. To avoid unintended dietary outcomes, it is vital that consumers make pragmatic decisions regarding dietary replacements for cow’s milk.
Prebiotic Effects of Partially Hydrolyzed Guar Gum on the Composition and Function of the Human Microbiota—Results from the PAGODA Trial
Authors: Reider Simon J. , Moosmang Simon , Tragust Judith , Trgovec-Greif Lovro , Tragust Simon , Perschy Lorenz , Przysiecki Nicole , Sturm Sonja , Tilg Herbert , Stuppner Hermann , Rattei Thomas , Moschen Alexander R.
Published: April 2020

(1) Background: Alterations in the structural composition of the human gut microbiota have been identified in various disease entities along with exciting mechanistic clues by reductionist gnotobiotic modeling. Improving health by beneficially modulating an altered microbiota is a promising treatment approach. Prebiotics, substrates selectively used by host microorganisms conferring a health benefit, are broadly used for dietary and clinical interventions. Herein, we sought to investigate the microbiota-modelling effects of the soluble fiber, partially hydrolyzed guar gum (PHGG). (2) Methods: We performed a 9 week clinical trial in 20 healthy volunteers that included three weeks of a lead-in period, followed by three weeks of an intervention phase, wherein study subjects received 5 g PHGG up to three times per day, and concluding with a three-week washout period. A stool diary was kept on a daily basis, and clinical data along with serum/plasma and stool samples were collected on a weekly basis. PHGG-induced alterations of the gut microbiota were studied by 16S metagenomics of the V1–V3 and V3–V4 regions. To gain functional insight, we further studied stool metabolites using nuclear magnetic resonance (NMR) spectroscopy. (3) Results: In healthy subjects, PHGG had significant effects on stool frequency and consistency. These effects were paralleled by changes in α- (species evenness) and β-diversity (Bray–Curtis distances), along with increasing abundances of metabolites including butyrate, acetate and various amino acids. On a taxonomic level, PHGG intake was associated with a bloom in Ruminococcus, Fusicatenibacter, Faecalibacterium and Bacteroides and a reduction in Roseburia, Lachnospiracea and Blautia. The majority of effects disappeared after stopping the prebiotic and most effects tended to be more pronounced in male participants. (4) Conclusions: Herein, we describe novel aspects of the prebiotic PHGG on compositional and functional properties of the healthy human microbiota.
Contribution of 100% Fruit Juice to Micronutrient Intakes in the United States, United Kingdom and Brazil
Authors: Mitchell Ellen S. , Musa-Veloso Kathy , Fallah Shafagh , Lee Han Youl , Chavez Peter J. De , Gibson Sigrid
Published: April 2020

The contribution of 100% fruit juice (FJ) to the total daily intakes of energy, sugars, and select vitamins and minerals and to the recommended dietary allowances (RDAs) or adequate intake (AI) of these micronutrients was assessed in individuals reporting the consumption of 100% FJ in the national dietary intake surveys of the United States (U.S.; n = 8661), the United Kingdom (UK; n = 2546) and Brazil (n = 34,003). Associations of 100% FJ intake with the odds of being overweight or obese also were assessed. Data from the U.S. National Health and Nutrition Examination Survey (2013–2014), the UK National Diet and Nutrition Survey (2012–2014), and Brazil’s Pesquisa de Orçamentos Familiares (2008–2009) were used, and all analyses were limited to individuals reporting consumption of 100% FJ on at least one day of the dietary intake survey. Approximately 34%, 37%, and 42% of individuals surveyed reported the consumption of 100% FJ on at least one day of the dietary intake survey in the U.S., UK, and Brazil, respectively, and the average daily intakes of 100% FJ were 184 g, 130 g, and 249 g, respectively. Across the 3 countries, 100% FJ contributed to 3–6% of total energy intakes, 12–31% of total sugar intakes, 21–54% of total vitamin C intakes, 1–12% of total vitamin A intakes, 4–15% of total folate intakes, 7–17% of total potassium intakes, 2–7% of total calcium intakes, and 4–12% of total magnesium intakes. In a multivariate logistic regression model, juice intake was associated with a significant reduction in the odds of being overweight or obese in UK adults (OR = 0.79; 0.63, 0.99), and significant increases in the odds of being overweight or obese in UK children (OR = 1.16; 1.01, 1.33) and Brazilian adults (OR = 1.04; 1.00, 1.09). Nutrient contributions of 100% FJ vary according to regional intake levels. In all three countries studied, 100% FJ contributed to more than 5% of the RDAs for vitamin C and folate. In the U.S. and Brazil, 100% FJ contributed to more than 5% of the RDA for magnesium and more than 5% of the AI for potassium.
Complementary Feeding in Preterm Infants: Where Do We Stand?
Authors: Baldassarre Maria Elisabetta , Giannì Maria Lorella , Di Mauro Antonio , Mosca Fabio , Laforgia Nicola
Published: April 2020

Currently, about 15 million preterm births occur annually worldwide; over 500,000 in Europe and 32,000 in Italy, accounting for 7–11% of total births, with the highest incidence in low-income states [...]
Anti-Obesity Effects of Petasites japonicus (Meowi) Ethanol Extract on RAW 264.7 Macrophages and 3T3-L1 Adipocytes and Its Characterization of Polyphenolic Compounds
Authors: Ahn Eun Mi , Asamenew Gelila , Kim Heon Woong , Lee Sang Hoon , Yoo Seon-Mi , Cho Soo-Muk , Cha Youn-Soo , Kang Min-Sook
Published: April 2020

Koreans have been consuming Petasites Japonicus (PJ) as food. Although the therapeutic effect of PJ on allergic or inflammatory reactions associated with asthma has been proven, its effect on obesity is unclear. Therefore, the present study was aimed to assess the obesity related anti-inflammatory and anti-adipogenic effects of ethanol extract PJ (EPJ) on the inflammatory response in RAW 264.7 macrophages and on differentiation in 3T3-L1 adipocytes. In addition, the polyphenolic compound was quantitatively characterized from the EPJ using ultra performance liquid chromatography coupled with diode array detector, quadrupole time-of-flight-mass spectrometry (UPLC-DAD-QToF-MS). In RAW 264.7 or 3T3-L1, reduction of nitric oxide (in macrophages) production as well as monocyte chemoattractant protein-1 and tumor necrosis factor-α were observed. Treatment of EPJ in adipocyte differentiation showed an improvement in adiponectin and lipid accumulation and a significant reduction of PPARγ and FABP-4 mRNA expression levels. On the other hand, mRNA expression of UCP-1, PPARα, and ACO increased in the EPJ treated group. In addition, a total of 26 polyphenolic compounds were detected and of which 12 are reported for the first time from PJ. The higher content of diverse polyphenolic compounds presented in EPJ might be responsible for the observed anti-inflammatory and anti-adipogenic effect. These results suggest that PJ is valuable in improving obesity-related inflammatory responses.
Beneficial Effects of Time-Restricted Eating on Metabolic Diseases: A Systemic Review and Meta-Analysis
Authors: Moon Shinje , Kang Jiseung , Kim Sang Hyun , Chung Hye Soo , Kim Yoon Jung , Yu Jae Myung , Cho Sung Tae , Oh Chang-Myung , Kim Tae
Published: April 2020

Various behavioral and physiological pathways follow a pre-determined, 24 hour cycle known as the circadian rhythm. Metabolic homeostasis is regulated by the circadian rhythm. Time-restricted eating (TRE) is a type of intermittent fasting based on the circadian rhythm. In this study, we aim to analyze systemically the effects of TRE on body weight, body composition, and other metabolic parameters. We reviewed articles from PubMed, EMBASE, and the Cochrane Library to identify clinical trials that compared TRE to a regular diet. We included 19 studies for meta-analysis. Participants following TRE showed significantly reduced body weight (mean difference (MD), −0.90; 95% confidence interval (CI): −1.71 to −0.10) and fat mass (MD: −1.58, 95% CI: −2.64 to −0.51), while preserving fat-free mass (MD, −0.24; 95% CI: −1.15 to 0.67). TRE also showed beneficial effects on cardiometabolic parameters such as blood pressure (systolic BP, MD, −3.07; 95% CI: −5.76 to −0.37), fasting glucose concentration (MD, −2.96; 95% CI, −5.60 to −0.33), and cholesterol profiles (triglycerides, MD: −11.60, 95% CI: −23.30 to −0.27). In conclusion, TRE is a promising therapeutic strategy for controlling weight and improving metabolic dysfunctions in those who are overweight or obese. Further large-scale clinical trials are needed to confirm these findings and the usefulness of TRE.
Efficiency of Vitamin D Supplementation in Healthy Adults is Associated with Body Mass Index and Baseline Serum 25-Hydroxyvitamin D Level
Authors: Žmitek Katja , Hribar Maša , Hristov Hristo , Pravst Igor
Published: April 2020

Vitamin D (VitD) has a critical role in phosphorous–calcium metabolism as well as an important role in the immune system. In the human body, VitD is synthesized as cholecalciferol in the skin, but this process requires sunlight (UVB) radiation. Numerous reports showed high prevalence of VitD deficiency, particularly during the winter season, indicating the importance of VitD supplementation. Various factors can affect the absorption of VitD, including dosage and formulation. The primary study objective was to examine the efficiency of supplementation with three different formulations containing cholecalciferol in comparison with the control group. The secondary objective was to identify other factors affecting increase in serum 25-OH-VitD. A randomized controlled intervention study was conducted in Slovenia during wintertime (January– March) on 105 apparently healthy subjects (aged 18–65 years) with suboptimal VitD status (25-OH-VitD 30–50 nmol/L). Subjects were randomized into four groups: three treatment groups receiving (A) capsules with starch-adsorbed VitD, (B) oil-based Valens VitD oral spray, or (C) water-based Valens VitD oral spray and a control group (D) which did not receive supplemental VitD. Two months of supplementation with cholecalciferol (1000 IU; 25 µg daily) resulted in significant increase in serum 25-OH-VitD levels in comparison with control group (pooled Δc 32.8 nmol/L; 95% CI: 23.0, 42.5, p < 0.0001). While we did not observe any significant differences between the tested formulations, the efficiency of supplementation was associated with body mass index and baseline serum 25-OH-VitD level. Higher supplementation efficiency was observed in participants with normal body weight (BMI < 25) and in those with more pronounced VitD insufficiency. We also determined that tested dosage was not sufficient to achieve recommended 25-OH-VitD levels in all subjects.
The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms
Authors: Alanagreh Lo’ai , Alzoughool Foad , Atoum Manar
Published: April 2020

The emerging coronavirus disease (COVID-19) swept across the world, affecting more than 200 countries and territories. Genomic analysis suggests that the COVID-19 virus originated in bats and transmitted to humans through unknown intermediate hosts in the Wuhan seafood market, China, in December of 2019. This virus belongs to the Betacoronavirus group, the same group of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), and for the similarity, it was named SARS-CoV-2. Given the lack of registered clinical therapies or vaccines, many physicians and scientists are investigating previously used clinical drugs for COVID-19 treatment. In this review, we aim to provide an overview of the CoVs origin, pathogenicity, and genomic structure, with a focus on SARS-CoV-2. Besides, we summarize the recently investigated drugs that constitute an option for COVID-19 treatment.
Serological Survey and Molecular Typing Reveal New Leptospira Serogroup Pomona Strains among Pigs of Northern Italy
Authors: Bertasio Cristina , Papetti Alice , Scaltriti Erika , Tagliabue Silvia , D’Incau Mario , Boniotti Maria Beatrice
Published: April 2020

Swine act as both maintenance and incidental hosts of pathogenic Leptospira spp. Here, a serological test was performed on 131,660 pig sera collected between 2002 and 2017 from 4715 farms in Northern Italy. A positivity rate of 13.05% was determined. Australis was the most frequently identified serogroup (77.29%), followed by Pomona (18.47%), Tarassovi (1.51%) and Icterohaemorrhagie (1.40%). Culture isolation and real-time Polymerase chain reaction (PCR) were carried out on 347 kidneys and 470 clinical samples, respectively. Overall, 133 strains were cultured successfully and 43 randomly chosen isolates were identified as serogroup Pomona. Multi-locus sequence typing (MLST) revealed that 41 isolates and 8 DNA extracted from biological samples belonged to sequence type 140. Using a multiple-locus, variable-number tandem repeat analysis, 43 samples produced identical profiles but, after 2014, three new Leptospira interrogans serogroup Pomona genotypes were observed. Interestingly, two isolates showed new MLST profiles and an unclassified identification by monoclonal antibodies. The 16S rRNA gene sequencing clustered them into L. kirschneri species and a core genome MLST analysis revealed an allelic identity of 96% compared with Mozdok strains. Genotyping allowed us to discriminate leptospires and to identify new emerging strains. The accurate identification of infective strains is required for formulating preventive methods and intervention strategies.
Effect of Litter Treatment on Campylobacter jejuni in Broilers and on Cecal Microbiota
Authors: Thépault Amandine , Roulleau Xavier , Loiseau Pauline , Cauquil Laurent , Poezevara Typhaine , Hyronimus Bertrand , Quesne Ségolène , Souchaud Florent , Keita Alassane , Chemaly Marianne , Guyard-Nicodème Muriel
Published: April 2020

Since 2018, when a process hygiene criterion for Campylobacter in broilers at the slaughterhouse was implemented across Europe, efforts to reduce Campylobacter at farm level have increased. Despite numerous studies aiming to reduce Campylobacter colonization in broilers, no efficient control strategy has been identified so far. The present work assessed first the efficacy of a commercial litter treatment to reduce Campylobacter colonization in broilers during two in-vivo trials and second, its impact on cecal microbiota. The treatment does not affect broiler growth and no effect on Campylobacter counts was observed during the in-vivo trials. Nevertheless, cecal microbiota were affected by the treatment. Alpha and beta diversity were significantly different for the control and litter-treated groups on day 35. In addition, several taxa were identified as significantly associated with the different experimental groups. Further work is needed to find a suitable control measure combining different strategies in order to reduce Campylobacter.
Polymyxin Delivery Systems: Recent Advances and Challenges
Authors: Dubashynskaya Natallia V. , Skorik Yury A.
Published: April 2020

Polymyxins are vital antibiotics for the treatment of multiresistant Gram-negative ESKAPE pathogen infections. However, their clinical value is limited by their high nephrotoxicity and neurotoxicity, as well as their poor permeability and absorption in the gastrointestinal tract. This review focuses on various polymyxin delivery systems that improve polymyxin bioavailability and reduce drug toxicity through targeted and controlled release. Currently, the most suitable systems for improving oral, inhalation, and parenteral polymyxin delivery are polymer particles, liposomes, and conjugates, while gels, polymer fibers, and membranes are attractive materials for topical administration of polymyxin for the treatment of infected wounds and burns. In general, the application of these systems protects polymyxin molecules from the negative effects of both physiological and pathological factors while achieving higher concentrations at the target site and reducing dosage and toxicity. Improving the properties of polymyxin will be of great interest to researchers who are focused on developing antimicrobial drugs that show increased efficacy and safety.
Investigating the Effect of Encapsulation Processing Parameters on the Viability of Therapeutic Viruses in Electrospraying
Authors: Sanders Tayo , Milicic Anita , Stride Eleanor
Published: April 2020

The ability of viruses to introduce genetic material into cells can be usefully exploited in a variety of therapies and also vaccination. Encapsulating viruses to limit inactivation by the immune system before reaching the desired target and allowing for controlled release is a promising strategy of delivery. Conventional encapsulation methods, however, can significantly reduce infectivity. The aim of this study was to investigate electrospraying as an alternative encapsulation technique. Two commonly used therapeutic viruses, adenovirus (Ad) and modified vaccinia Ankara (MVA), were selected. First, solutions containing the viruses were electrosprayed in a single needle configuration at increasing voltages to examine the impact of the electric field. Second, the effect of exposing the viruses to pure organic solvents was investigated and compared to that occurring during coaxial electrospraying. Infectivity was determined by measuring the luminescence produced from lysed A549 cells after incubation with treated virus. Neither Ad nor MVA exhibited any significant loss in infectivity when electrosprayed within the range of electrospraying parameters relevant for encapsulation. A significant decrease in infectivity was only observed when MVA was electrosprayed at the highest voltage, 24 kV, and when MVA and Ad were exposed to selected pure organic solvents. Thus, it was concluded that electrospraying would be a viable method for virus encapsulation.
Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing
Authors: Blokland Kaj E. C. , Waters David W. , Schuliga Michael , Read Jane , Pouwels Simon D. , Grainge Christopher L. , Jaffar Jade , Westall Glen , Mutsaers Steven E. , Prêle Cecilia M. , Burgess Janette K. , Knight Darryl A.
Published: April 2020

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive accumulation of lung fibroblasts (LFs) and collagen in the lung parenchyma. The mechanisms that underlie IPF pathophysiology are thought to reflect repeated alveolar epithelial injury leading to an aberrant wound repair response. Recent work has shown that IPF-LFs display increased characteristics of senescence including growth arrest and a senescence-associated secretory phenotype (SASP) suggesting that senescent LFs contribute to dysfunctional wound repair process. Here, we investigated the influence of senescent LFs on alveolar epithelial cell repair responses in a co-culture system. Alveolar epithelial cell proliferation was attenuated when in co-culture with cells or conditioned media from, senescence-induced control LFs or IPF-LFs. Cell-cycle analyses showed that a larger number of epithelial cells were arrested in G2/M phase when co-cultured with IPF-LFs, than in monoculture. Paradoxically, the presence of LFs resulted in increased A549 migration after mechanical injury. Our data suggest that senescent LFs may contribute to aberrant re-epithelialization by inhibiting proliferation in IPF.
Ionic Liquid-In-Oil Microemulsions Prepared with Biocompatible Choline Carboxylic Acids for Improving the Transdermal Delivery of a Sparingly Soluble Drug
Authors: Islam Md. Rafiqul , Chowdhury Md. Raihan , Wakabayashi Rie , Kamiya Noriho , Moniruzzaman Muhammad , Goto Masahiro
Published: April 2020

The transdermal delivery of sparingly soluble drugs is challenging due to of the need for a drug carrier. In the past few decades, ionic liquid (IL)-in-oil microemulsions (IL/O MEs) have been developed as potential carriers. By focusing on biocompatibility, we report on an IL/O ME that is designed to enhance the solubility and transdermal delivery of the sparingly soluble drug, acyclovir. The prepared MEs were composed of a hydrophilic IL (choline formate, choline lactate, or choline propionate) as the non-aqueous polar phase and a surface-active IL (choline oleate) as the surfactant in combination with sorbitan laurate in a continuous oil phase. The selected ILs were all biologically active ions. Optimized pseudo ternary phase diagrams indicated the MEs formed thermodynamically stable, spherically shaped, and nano-sized (<100 nm) droplets. An in vitro drug permeation study, using pig skin, showed the significantly enhanced permeation of acyclovir using the ME. A Fourier transform infrared spectroscopy study showed a reduction of the skin barrier function with the ME. Finally, a skin irritation study showed a high cell survival rate (>90%) with the ME compared with Dulbecco’s phosphate-buffered saline, indicates the biocompatibility of the ME. Therefore, we conclude that IL/O ME may be a promising nano-carrier for the transdermal delivery of sparingly soluble drugs.
The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability
Authors: van der Merwe Jannes , Steenekamp Jan , Steyn Dewald , Hamman Josias
Published: April 2020

Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract. The oral bioavailability of these compounds is usually very low as a result of their poor solubility properties. In order to improve the bioavailability of these poorly soluble drugs, formulation strategies have been applied as a means to improve their aqueous solubility and dissolution rates. With respect to formulation approaches, excipients can be incorporated in the formulation to assist in the dissolution process of the drug, or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms. This paper provides an overview of selected excipients (e.g., alkalinizing agents, surfactants and sugars) that can be used in formulations to increase the dissolution rate as well as specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions. These formulation approaches are discussed with available examples with specific reference to positive outcomes in terms of drug solubility and bioavailability enhancement.
Characterization of the Blood–Brain Barrier Integrity and the Brain Transport of SN-38 in an Orthotopic Xenograft Rat Model of Diffuse Intrinsic Pontine Glioma
Authors: Chaves Catarina , Declèves Xavier , Taghi Meryam , Menet Marie-Claude , Lacombe Joelle , Varlet Pascale , Olaciregui Nagore G. , Carcaboso Angel M. , Cisternino Salvatore
Published: April 2020

The blood–brain barrier (BBB) hinders the brain delivery of many anticancer drugs. In pediatric patients, diffuse intrinsic pontine glioma (DIPG) represents the main cause of brain cancer mortality lacking effective drug therapy. Using sham and DIPG-bearing rats, we analyzed (1) the brain distribution of 3-kDa-Texas red-dextran (TRD) or [14C]-sucrose as measures of BBB integrity, and (2) the role of major ATP-binding cassette (ABC) transporters at the BBB on the efflux of the irinotecan metabolite [3H]-SN-38. The unaffected [14C]-sucrose or TRD distribution in the cerebrum, cerebellum, and brainstem regions in DIPG-bearing animals suggests an intact BBB. Targeted proteomics retrieved no change in P-glycoprotein (P-gp), BCRP, MRP1, and MRP4 levels in the analyzed regions of DIPG rats. In vitro, DIPG cells express BCRP but not P-gp, MRP1, or MRP4. Dual inhibition of P-gp/Bcrp, or Mrp showed a significant increase on SN-38 BBB transport: Cerebrum (8.3-fold and 3-fold, respectively), cerebellum (4.2-fold and 2.8-fold), and brainstem (2.6-fold and 2.2-fold). Elacridar increased [3H]-SN-38 brain delivery beyond a P-gp/Bcrp inhibitor effect alone, emphasizing the role of another unidentified transporter in BBB efflux of SN-38. These results confirm a well-preserved BBB in DIPG-bearing rats, along with functional ABC-transporter expression. The development of chemotherapeutic strategies to circumvent ABC-mediated BBB efflux are needed to improve anticancer drug delivery against DIPG.
NAFLD Aggravates Septic Shock Due to Inadequate Adrenal Response and 11β-HSDs Dysregulation in Rats
Authors: Huang Hui-Chun , Tsai Ming-Hung , Lee Fa-Yauh , Lin Te-Yueh , Chang Ching-Chih , Chuang Chiao-Lin , Hsu Shao-Jung , Hou Ming-Chih , Huang Yi-Hsiang
Published: April 2020

Background: Non-alcoholic fatty liver disease (NAFLD) is linked with metabolic syndrome. Previous studies showed that obesity may disrupt adrenal function and adversely affect its counter-regulations against shock. This study hence evaluated adrenal function abnormalities in NAFLD with shock. Methods: Sprague-Dawley rats were fed with regular chow-diet (control) or high fat diet (HFD, 60% energy derived from fat). Blood tests were performed at the end of the 4th, 6th and 8th week, respectively. Experiments were performed at the end of the 8th week. Results: HFD rats developed NAFLD. HFD rats had 27% and 51% increase in plasma corticosterone at the 6th and 8th week in usual status. However, HFD rats had 5 times more reduction of mean arterial pressure in response to lipopolysaccharide-induced sepsis as compared to control rats. The corticosterone increment ratio was also lower in HFD rats, even after ACTH administration. 11β-HSD system tended to generate more corticosterone in HFD rats under hemodynamic stable status without shock and the trend was lost in HFD rats with septic shock. Conclusion: Rats with NAFLD had profound septic shock due to inadequate corticosterone response. This is, at least partly, due to 11β-HSDs dysregulation in sepsis.
In-Depth Characterization of EpiIntestinal Microtissue as a Model for Intestinal Drug Absorption and Metabolism in Human
Authors: Cui Yunhai , Claus Stephanie , Schnell David , Runge Frank , MacLean Caroline
Published: April 2020

The Caco-2 model is a well-accepted in vitro model for the estimation of fraction absorbed in human intestine. Due to the lack of cytochrome P450 3A4 (CYP3A4) activities, Caco-2 model is not suitable for the investigation of intestinal first-pass metabolism. The purpose of this study is to evaluate a new human intestine model, EpiIntestinal microtissues, as a tool for the prediction of oral absorption and metabolism of drugs in human intestine. The activities of relevant drug transporters and drug metabolizing enzymes, including MDR1 P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), CYP3A4, CYP2J2, UDP-glucuronosyltransferases (UGT), carboxylesterases (CES), etc., were detected in functional assays with selective substrates and inhibitors. Compared to Caco-2, EpiIntestinal microtissues proved to be a more holistic model for the investigation of drug absorption and metabolism in human gastrointestinal tract.
Polymer-Drug Conjugate, a Potential Therapeutic to Combat Breast and Lung Cancer
Authors: Alven Sibusiso , Nqoro Xhamla , Buyana Buhle , Aderibigbe Blessing A.
Published: April 2020

Cancer is a chronic disease that is responsible for the high death rate, globally. The administration of anticancer drugs is one crucial approach that is employed for the treatment of cancer, although its therapeutic status is not presently satisfactory. The anticancer drugs are limited pharmacologically, resulting from the serious side effects, which could be life-threatening. Polymer drug conjugates, nano-based drug delivery systems can be utilized to protect normal body tissues from the adverse side effects of anticancer drugs and also to overcome drug resistance. They transport therapeutic agents to the target cell/tissue. This review article is based on the therapeutic outcomes of polymer-drug conjugates against breast and lung cancer.
Mutagenic Effect of Three Ion Beams on Rice and Identification of Heritable Mutations by Whole Genome Sequencing
Authors: Zheng Yunchao , Li Shan , Huang Jianzhong , Fu Haowei , Zhou Libin , Furusawa Yoshiya , Shu Qingyao
Published: April 2020

High-energy ion beams are known to be an effective and unique type of physical mutagen in plants. However, no study on the mutagenic effect of argon (Ar) ion beam radiation on rice has been reported. Genome-wide studies on induced mutations are important to comprehend their characteristics for establishing knowledge-based protocols for mutation induction and breeding, which are still very limited in rice. The present study aimed to investigate the mutagenic effect of three ion beams, i.e., Ar, carbon (C) and neon (Ne) on rice and identify and characterize heritable induced mutations by the whole genome sequencing of six M4 plants. Dose-dependent damage effects were observed on M1 plants, which were developed from ion beam irradiated dry seeds of two indica (LH15, T23) and two japonica (DS551, DS48) rice lines. High frequencies of chlorophyll-deficient seedlings and male-sterile plants were observed in all M2 populations (up to ~30% on M1 plant basis); plants from the seeds of different panicles of a common M1 plant appeared to have different mutations; the whole genome-sequencing demonstrated that there were 236–453 mutations in each of the six M4 plants, including single base substitutions (SBSs) and small insertion/deletions (InDels), with the number of SBSs ~ 4–8 times greater than that of InDels; SBS and InDel mutations were distributed across different genomic regions of all 12 chromosomes, however, only a small number of mutations (0–6) were present in exonic regions that might have an impact on gene function. In summary, the present study demonstrates that Ar, C and Ne ion beam radiation are all effective for mutation induction in rice and has revealed at the genome level the characteristics of the mutations induced by the three ion beams. The findings are of importance to the efficient use of ion beam radiation for the generation and utilization of mutants in rice.
The Product Specificities of Maize Terpene Synthases TPS4 and TPS10 Are Determined Both by Active Site Amino Acids and Residues Adjacent to the Active Site
Authors: Köllner Tobias G. , Degenhardt Jörg , Gershenzon Jonathan
Published: April 2020

Terpene synthases make up a large family of enzymes that convert prenyl diphosphates into an enormous variety of terpene skeletons. Due to their electrophilic reaction mechanism—which involves the formation of carbocations followed by hydride shifts and skeletal rearrangements—terpene synthases often produce complex mixtures of products. In the present study, we investigate amino acids that determine the product specificities of the maize terpene synthases TPS4 and TPS10. The enzymes showed 57% amino acid similarity and produced different mixtures of sesquiterpenes. Sequence comparisons and structure modeling revealed that out of the 43 amino acids forming the active site cavity, 17 differed between TPS4 and TPS10. While combined mutation of these 17 residues in TPS4 resulted in an enzyme with a product specificity similar to TPS10, the additional mutation of two amino acids next to the active site led to a nearly complete conversion of TPS4 into TPS10. These data demonstrate that the different product specificities of TPS4 and TPS10 are determined not only by amino acids forming the active site cavity, but also by neighboring residues that influence the conformation of active site amino acids.
Quantification of Spectral Perception of Plants with Light Absorption of Photoreceptors
Authors: Kang Woo Hyun , Kim Jaewoo , Yoon Hyo In , Son Jung Eek
Published: April 2020

Although plant responses to artificial lighting spectra often produce abnormal morphogenesis and reduced productivity, no quantification method to determine how plants perceive and respond to light has been available. Our objective in this study was to test whether a plant’s spectral perception can be quantified using the light absorption of its major photoreceptors, phytochrome, cryptochrome, and phototropin. We developed an artificial solar lamp and three different light sources, based on a high-pressure sodium lamp, a fluorescent lamp, and red and blue light-emitting diodes, whose absorption by photoreceptors was equal to that of the standard solar spectrum. Cucumber plants grown under the artificial solar and developed light sources showed normal photomorphogenesis and were indistinguishable from each other. Plants grown under unmodified commercial light sources had abnormal photomorphogenesis that made them short and small. The photosynthetic rate was higher under the unmodified light sources; however, dry masses were highest under the artificial solar and modified light sources, indicating that the cucumber plants are optimized to the solar spectrum. Our results clearly demonstrate that the spectral perceptions of plants can be quantified using the light absorption of their photoreceptors, not visual color or spectra. We expect that our findings will contribute to a better understanding of plant perceptions of and responses to light quality, and improve the productivity of plants cultivated under artificial light.
Molecular Verification of the UK National Collection of Cultivated Liriope and Ophiopogon Plants
Authors: Masiero Eva , Banik Dipanwita , Abson John , Greene Paul , Slater Adrian , Sgamma Tiziana
Published: April 2020

A collection of cultivated Liriope and Ophiopogon plants was established in 1996–1998 and subsequently hosted at a horticultural college. Uncertainties about the identification of the accessions, compounded by potential errors in propagation and labelling have led to waning confidence in the identities of the plants in the collection. The potential for using DNA barcoding to determine the species identities of the accessions was investigated. The DNA barcode regions of the plastid ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) and nuclear ribosomal internal transcribed spacer (nrITS) were amplified. DNA sequence analysis allowed the sequences of the accessions to be compared to reference sequences in public databases. A simple haplotype map of the characteristic polymorphic positions in the rbcL regions was used to clearly distinguish between the two genera and assign Ophiopogon accessions to individual species or sub-groups of species. The ITS sequence data confirmed these genus and species assignations and provided greater resolution to distinguish between closely related species. The combination of two DNA barcodes allowed most of the accessions to be assigned to individual species. This molecular verification confirmed the identity of about 70% of the accessions, with the remaining 30% demonstrating a range of mistaken identities at the species and genus levels.