bluuebunny/crossref_metadata_2025 huggingface dataset:
Correction: Yoo, J.Y., et al. Gut Microbiota and Immune System Interactions. Microorganisms 2020, 8, 1587
Authors: Yoo Ji Youn , Groer Maureen , Dutra Samia Valeria Ozorio , Sarkar Anujit , McSkimming Daniel Ian
Published: December 2020

Corrections have been made to “Gut Microbiota and Immune System Interactions” [...]
Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds
Authors: Grymel Mirosława , Pastuch-Gawołek Gabriela , Lalik Anna , Zawojak Mateusz , Boczek Seweryn , Krawczyk Monika , Erfurt Karol
Published: December 2020

Pentacyclic lupane-type triterpenoids, such as betulin and its synthetic derivatives, display a broad spectrum of biological activity. However, one of the major drawbacks of these compounds as potential therapeutic agents is their high hydrophobicity and low bioavailability. On the other hand, the presence of easily transformable functional groups in the parent structure makes betulin have a high synthetic potential and the ability to form different derivatives. In this context, research on the synthesis of new betulin derivatives as conjugates of naturally occurring triterpenoid with a monosaccharide via a linker containing a heteroaromatic 1,2,3-triazole ring was presented. It has been shown that copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition reaction (CuAAC) provides an easy and effective way to synthesize new molecular hybrids based on natural products. The chemical structures of the obtained betulin glycoconjugates were confirmed by spectroscopic analysis. Cytotoxicity of the obtained compounds was evaluated on a human breast adenocarcinoma cell line (MCF-7) and colorectal carcinoma cell line (HCT 116). The obtained results show that despite the fact that the obtained betulin glycoconjugates do not show interesting antitumor activity, the idea of adding a sugar unit to the betulin backbone may, after some modifications, turn out to be correct and allow for the targeted transport of betulin glycoconjugates into the tumor cells.
Correlation between Ferromagnetic Layer Easy Axis and the Tilt Angle of Self Assembled Chiral Molecules
Authors: Sukenik Nir , Tassinari Francesco , Yochelis Shira , Millo Oded , Baczewski Lech Tomasz , Paltiel Yossi
Published: December 2020

The spin–spin interactions between chiral molecules and ferromagnetic metals were found to be strongly affected by the chiral induced spin selectivity effect. Previous works unraveled two complementary phenomena: magnetization reorientation of ferromagnetic thin film upon adsorption of chiral molecules and different interaction rate of opposite enantiomers with a magnetic substrate. These phenomena were all observed when the easy axis of the ferromagnet was out of plane. In this work, the effects of the ferromagnetic easy axis direction, on both the chiral molecular monolayer tilt angle and the magnetization reorientation of the magnetic substrate, are studied using magnetic force microscopy. We have also studied the effect of an applied external magnetic field during the adsorption process. Our results show a clear correlation between the ferromagnetic layer easy axis direction and the tilt angle of the bonded molecules. This tilt angle was found to be larger for an in plane easy axis as compared to an out of plane easy axis. Adsorption under external magnetic field shows that magnetization reorientation occurs also after the adsorption event. These findings show that the interaction between chiral molecules and ferromagnetic layers stabilizes the magnetic reorientation, even after the adsorption, and strongly depends on the anisotropy of the magnetic substrate. This unique behavior is important for developing enantiomer separation techniques using magnetic substrates.
Effects of Deacidification on Composition of Schisandra chinensis Ethanolic Extract and Studies on Acute Toxicity in Mice
Authors: Hu Gaosheng , Qi Zhuangbo , Wang Anhua , Jia Jingming
Published: December 2020

Schisandra chinensis Fructus (SCF), a well-known traditional medicinal material, is a rich source of dibenzocyclooctene type lignans and polyphenols, which are important ingredients in SCF and show various activities. SCF also contains about 18% organic acids, mainly citric acid, which makes the fruit and extract taste extremely sour and limited its application in beverages or food industries. In the present study, a chemical deacidification method was applied to defatted and non-defatted ethanol extract of SCF, and the effects on organic acid, lignans, and phenolic compounds were evaluated. Free radical scavenging activity and acute toxicity in mice before and after deacidification were also compared. Our results demonstrated that chemical deacidification significantly decreased the contents of organic acid and lignan compounds and markedly improves the safety of the ethanol extract of SCF, which will facilitate the comprehensive utilization of SCF extract in food and beverage industries.
Highly Sensitive Gas Sensing Material for Environmentally Toxic Gases Based on Janus NbSeTe Monolayer
Authors: Singh Deobrat , Ahuja Rajeev
Published: December 2020

Recently, a new family of the Janus NbSeTe monolayer has exciting development prospects for two-dimensional (2D) asymmetric layered materials that demonstrate outstanding properties for high-performance nanoelectronics and optoelectronics applications. Motivated by the fascinating properties of the Janus monolayer, we have studied the gas sensing properties of the Janus NbSeTe monolayer for CO, CO2, NO, NO2, H2S, and SO2 gas molecules using first-principles calculations that will have eminent application in the field of personal security, protection of the environment, and various other industries. We have calculated the adsorption energies and sensing height from the Janus NbSeTe monolayer surface to the gas molecules to detect the binding strength for these considered toxic gases. In addition, considerable charge transfer between Janus monolayer and gas molecules were calculated to confirm the detection of toxic gases. Due to the presence of asymmetric structures of the Janus NbSeTe monolayer, the projected density of states, charge transfer, binding strength, and transport properties displayed distinct behavior when these toxic gases absorbed at Se- and Te-sites of the Janus monolayer. Based on the ultra-low recovery time in the order of μs for NO and NO2 and ps for CO, CO2, H2S, and SO2 gas molecules in the visible region at room temperature suggest that the Janus monolayer as a better candidate for reusable sensors for gas sensing materials. From the transport properties, it can be observed that there is a significant variation of I−V characteristics and sensitivity of the Janus NbSeTe monolayer before and after adsorbing gas molecules demonstrates the feasibility of NbSeTe material that makes it an ideal material for a high-sensitivity gas sensor.
Self-Assembled Few-Layered MoS2 on SnO2 Anode for Enhancing Lithium-Ion Storage
Authors: Nguyen Thang Phan , Kim Il Tae
Published: December 2020

SnO2 nanoparticles (NPs) have been used as reversible high-capacity anode materials in lithium-ion batteries, with reversible capacities reaching 740 mAh·g−1. However, large SnO2 NPs do not perform well in charge–discharge cycling. In this work, we report the incorporation of MoS2 nanosheet (NS) layers with SnO2 NPs. SnO2 NPs of ~5 nm in diameter synthesized by a facile hydrothermal precipitation method. Meanwhile, MoS2 NSs of a few hundreds of nanometers to a few micrometers in lateral size were produced by top-down chemical exfoliation. The self-assembly of the MoS2 NS layer on the gas–liquid interface was first demonstrated to achieve up to 80% coverage of the SnO2 NP anode surface. The electrochemical properties of the pure SnO2 NPs and MoS2-covered SnO2 NP anodes were investigated. The results showed that the SnO2 electrode with a single-layer MoS2 NS film exhibited better electrochemical performance than the pure SnO2 anode in lithium storage applications.
Thiolation of Chitosan Loaded over Super-Magnetic Halloysite Nanotubes for Enhanced Laccase Immobilization
Authors: Kadam Avinash A. , Sharma Bharat , Shinde Surendra K. , Ghodake Gajanan S. , Saratale Ganesh D. , Saratale Rijuta G. , Kim Do-Yeong , Sung Jung-Suk
Published: December 2020

This study focuses on the development of a nanosupport based on halloysite nanotubes (HNTs), Fe3O4 nanoparticles (NPs), and thiolated chitosan (CTs) for laccase immobilization. First, HNTs were modified with Fe3O4 NPs (HNTs-Fe3O4) by the coprecipitation method. Then, the HNTs-Fe3O4 surface was tuned with the CTs (HNTs-Fe3O4-CTs) by a simple refluxing method. Finally, the HNTs- Fe3O4-CTs surface was thiolated (-SH) (denoted as; HNTs- Fe3O4-CTs-SH) by using the reactive NHS-ester reaction. The thiol-modified HNTs (HNTs- Fe3O4-CTs-SH) were characterized by FE-SEM, HR-TEM, XPS, XRD, FT-IR, and VSM analyses. The HNTs-Fe3O4-CTs-SH was applied for the laccase immobilization. It gave excellent immobilization of laccase with 100% activity recovery and 144 mg/g laccase loading capacity. The immobilized laccase on HNTs-Fe3O4-CTs-SH (HNTs-Fe3O4-CTs-S-S-Laccase) exhibited enhanced biocatalytic performance with improved thermal, storage, and pH stabilities. HNTs-Fe3O4-CTs-S-S-Laccase gave outstanding repeated cycle capability, at the end of the 15th cycle, it kept 61% of the laccase activity. Furthermore, HNTs-Fe3O4-CTs-S-S-Laccase was applied for redox-mediated removal of textile dye DR80 and pharmaceutical compound ampicillin. The obtained result marked the potential of the HNTs-Fe3O4-CTs-S-S-Laccase for the removal of hazardous pollutants. This nanosupport is based on clay mineral HNTs, made from low-cost biopolymer CTs, super-magnetic in nature, and can be applied in laccase-based decontamination of environmental pollutants. This study also gave excellent material HNTs-Fe3O4-CTs-SH for other enzyme immobilization processes.
Impact of Inductively Coupled Plasma Etching Conditions on the Formation of Semi-Polar (\({11\overline{2}2}\)) and Non-Polar (\({11\overline{2}0}\)) GaN Nanorods
Authors: Coulon Pierre-Marie , Feng Peng , Wang Tao , Shields Philip
Published: December 2020

The formation of gallium nitride (GaN) semi-polar and non-polar nanostructures is of importance for improving light extraction/absorption of optoelectronic devices, creating optical resonant cavities or reducing the defect density. However, very limited studies of nanotexturing via dry etching have been performed, in comparison to wet etching. In this paper, we investigate the formation and morphology of semi-polar (112¯2) and non-polar (112¯0) GaN nanorods using inductively coupled plasma (ICP) etching. The impact of gas chemistry, pressure, temperature, radio-frequency (RF) and ICP power and time are explored. A dominant chemical component is found to have a significant impact on the morphology, being impacted by the polarity of the planes. In contrast, increasing the physical component enables the impact of crystal orientation to be minimized to achieve a circular nanorod profile with inclined sidewalls. These conditions were obtained for a small percentage of chlorine (Cl2) within the Cl2 + argon (Ar) plasma combined with a low pressure. Damage to the crystal was reduced by lowering the direct current (DC) bias through a reduction of the RF power and an increase of the ICP power.
Graphene Quantum Dot-TiO2 Photonic Crystal Films for Photocatalytic Applications
Authors: Apostolaki Maria-Athina , Toumazatou Alexia , Antoniadou Maria , Sakellis Elias , Xenogiannopoulou Evangelia , Gardelis Spiros , Boukos Nikos , Falaras Polycarpos , Dimoulas Athanasios , Likodimos Vlassis
Published: December 2020

Photonic crystal structuring has emerged as an advanced method to enhance solar light harvesting by metal oxide photocatalysts along with rational compositional modifications of the materials’ properties. In this work, surface functionalization of TiO2 photonic crystals by blue luminescent graphene quantum dots (GQDs), n–π* band at ca. 350 nm, is demonstrated as a facile, environmental benign method to promote photocatalytic activity by the combination of slow photon-assisted light trapping with GQD-TiO2 interfacial electron transfer. TiO2 inverse opal films fabricated by the co-assembly of polymer colloidal spheres with a hydrolyzed titania precursor were post-modified by impregnation in aqueous GQDs suspension without any structural distortion. Photonic band gap engineering by varying the inverse opal macropore size resulted in selective performance enhancement for both salicylic acid photocatalytic degradation and photocurrent generation under UV–VIS and visible light, when red-edge slow photons overlapped with the composite’s absorption edge, whereas stop band reflection was attenuated by the strong UVA absorbance of the GQD-TiO2 photonic films. Photoelectrochemical and photoluminescence measurements indicated that the observed improvement, which surpassed similarly modified benchmark mesoporous P25 TiO2 films, was further assisted by GQDs electron acceptor action and visible light activation to a lesser extent, leading to highly efficient photocatalytic films.
Carnitine Serum Levels in Frail Older Subjects
Authors: Malaguarnera Giulia , Catania Vito Emanuele , Bonfiglio Claudia , Bertino Gaetano , Vicari Enzo , Malaguarnera Michele
Published: December 2020

Frailty is an expression that reconciles and condenses loss of autonomy, both physical and cognitive decline and a wide spectrum of adverse outcomes due to aging. The decrease in physical and cognitive activity is associated with altered mitochondrial function, and energy loss and consequently morbidity and mortality. In this cross-sectional study, we evaluated the carnitine levels in frailty status. The mean serum concentrations of total carnitine (TC) were lower in frail elderly subjects than in prefrail ones (p = 0.0006), higher in frail vs. robust subjects (p < 0.0001), and higher in prefrail vs. robust subjects (p < 0.0001). The mean serum concentrations of free carnitine (FC) were lower in frail elderly subjects than in prefrail ones (p < 0.0001), lower in frail vs. robust subjects (p < 0.0001) and lower in prefrail vs. robust subjects (p = 0.0009). The mean serum concentrations of acylcarnitine (AC) were higher in frail elderly subjects than in prefrail ones (p = 0.054) and were higher in pre-frail vs. robust subjects (p = 0.0022). The mean urine concentrations of TC were lower in frail elderly subjects than in prefrail ones (p < 0.05) and lower in frail vs. robust subjects (p < 0.0001). The mean urine concentrations of free carnitine were lower in frail elderly vs. robust subjects (p < 0.05). The mean urine concentrations of acyl carnitines were lower in frail elderly subjects than those in both prefrail (p < 0.0001) and robust subjects (p < 0.0001). Conclusion: high levels of carnitine may have a favorable effect on the functional status and may treat the frailty status in older subjects.
Appetitive Traits in a Population-Based Study of Polish Adolescents within the PLACE-19 Study: Validation of the Adult Eating Behavior Questionnaire
Authors: Guzek Dominika , Skolmowska Dominika , Głąbska Dominika
Published: December 2020

Appetitive traits of food approach or food avoidance are commonly measured using the Adult Eating Behavior Questionnaire (AEBQ). However, there is no Polish version of the AEBQ validated for adolescents, and to the best of our knowledge, no study completed with the Polish version of the AEBQ has been published thus far. The present study aimed to validate the AEBQ in a population-based sample of Polish secondary school students and to assess differences in appetitive traits between boys and girls within the Polish Adolescents’ COVID-19 Experience (PLACE-19) Study. The PLACE-19 Study was conducted in a group of 2448 adolescents recruited in May 2020 through the random quota sampling of secondary schools. The AEBQ was used to assess food approach subscales (Food Responsiveness, Emotional Over-Eating, and Enjoyment of Food) and food avoidance subscales (Satiety Responsiveness, Emotional Under-Eating, Food Fussiness, and Slowness in Eating). To validate the questionnaire, the standardized factor loadings within confirmatory factor analysis (CFA) with weighted least squares (WLS) were analyzed, and invariance was verified. The CFA presented good model fit, with χ2 = 4826.105 (degrees of freedom (df) = 384), root mean square error of approximation (RMSEA) = 0.069 (90% confidence interval (CI): 0.067, 0.070), comparative fit index (CFI) = 0.90, and standardized root mean square residual (SRMR) = 0.08. The results revealed that, compared to the configural invariance model, the metric invariance model did not result in significantly decreased model fit, with ΔCFI = −0.002 and ΔRMSEA = −0.001, which were lower than the recommended cutoffs of 0.010 and 0.015, respectively. The scalar invariance model also did not result in significantly decreased fit of the model over the metric invariance model, with ΔCFI = −0.005 and ΔRMSEA = 0.000. Girls reported higher levels of Food Responsiveness (p < 0.0001), Emotional Over-Eating (p < 0.0001), Satiety Responsiveness (p < 0.0001), Emotional Under-Eating (p < 0.0001), and Slowness in Eating than boys (p < 0.0001), and the total AEBQ scores of girls were also higher (p < 0.0001). Positive inter-correlations were observed between all food approach subscales, as well as between Emotional Under-Eating and all food approach subscales for girls, boys, and the total sample; positive inter-correlations were also observed between the majority of food avoidance subscales. The present study confirmed the validity of the AEBQ in the studied population, and supported the associations between appetitive traits assessed using the AEBQ; it also indicated higher scores of both food approach and food avoidance subscales in girls than in boys in a population-based sample of Polish secondary school students.
Source and Composition in Amino Acid of Dietary Proteins in the Primary Prevention and Treatment of CKD
Authors: Letourneau Pierre , Bataille Stanislas , Chauveau Philippe , Fouque Denis , Koppe Laetitia
Published: December 2020

Nutrition is a cornerstone in the management of chronic kidney disease (CKD). To limit urea generation and accumulation, a global reduction in protein intake is routinely proposed. However, recent evidence has accumulated on the benefits of plant-based diets and plant-derived proteins without a clear understanding of underlying mechanisms. Particularly the roles of some amino acids (AAs) appear to be either deleterious or beneficial on the progression of CKD and its complications. This review outlines recent data on the role of a low protein intake, the plant nature of proteins, and some specific AAs actions on kidney function and metabolic disorders. We will focus on renal hemodynamics, intestinal microbiota, and the production of uremic toxins. Overall, these mechanistic effects are still poorly understood but deserve special attention to understand why low-protein diets provide clinical benefits and to find potential new therapeutic targets in CKD.
Passiflora incarnata in Neuropsychiatric Disorders—A Systematic Review
Authors: Janda Katarzyna , Wojtkowska Karolina , Jakubczyk Karolina , Antoniewicz Justyna , Skonieczna-Żydecka Karolina
Published: December 2020

Background: Stress is a natural response of the body, induced by factors of a physical (hunger, thirst, and infection) and/or psychological (perceived threat, anxiety, or concern) nature. Chronic, long-term stress may cause problems with sleep, concentration, and memory, as well as affective disorders. The passionflower (Passiflora incarnata) is a perennial plant with documented therapeutic properties. The literature data suggest that the passionflower itself, as well as its preparations, helps reduce stress and can therefore be helpful in the treatment of insomnia, anxiety, and depression. The objective of this systematic review was to evaluate Passiflora incarnata in terms of its neuropsychiatric effects. Methods: The scientific databases PubMed, ClinTrials.gov, and Embase were searched up to 22 October 2019. The search identified randomized clinical trials describing the effects of Passiflora incarnata in neuropsychiatric disorders. Results: The systematic review included nine clinical trials. The duration of the studies included in the analysis varied widely, from one day up to 30 days. Study participants were no less than 18 years old. In each of the papers, the effects of passionflower were measured by using a number of different tests and scales. The majority of studies reported reduced anxiety levels following the administration of Passiflora incarnata preparations, with the effect less evident in people with mild anxiety symptoms. No adverse effects, including memory loss or collapse of psychometric functions, were observed. Conclusion: Passiflora incarnata may be helpful in treating some symptoms in neuropsychiatric patients.
Nutritional and Behavioral Approaches to Body Composition and Low-Grade Chronic Inflammation Management for Older Adults in the Ordinary and COVID-19 Times
Authors: Ilich Jasminka Z.
Published: December 2020

As more insight is gained into personalized health care, the importance of personalized nutritional and behavioral approaches is even more relevant in the COVID-19 era, in addition to the need for further elucidation regarding several diseases/conditions. One of these concerning body composition (in this context; bone, lean and adipose tissue) is osteosarcopenic adiposity (OSA) syndrome. OSA occurs most often with aging, but also in cases of some chronic diseases and is exacerbated with the presence of low-grade chronic inflammation (LGCI). OSA has been associated with poor nutrition, metabolic disorders and diminished functional abilities. This paper addresses various influences on OSA and LGCI, as well as their mutual action on each other, and provides nutritional and behavioral approaches which could be personalized to help with either preventing or managing OSA and LGCI in general, and specifically in the time of the COVID-19 pandemic. Addressed in more detail are nutritional recommendations for and roles of macro- and micronutrients and bioactive food components; the microbiome; and optimal physical activity regimens. Other issues, such as food insecurity and nutritional inadequacy, circadian misalignment and shift workers are addressed as well. Since there is still a lack of longer-term primary studies in COVID-19 patients (either acute or recovered) and interventions for OSA improvement, this discussion is based on the existing knowledge, scientific hypotheses and observations derived from similar conditions or studies just being published at the time of this writing.
Animal and Human Vaccines against West Nile Virus
Authors: Saiz Juan-Carlos
Published: December 2020

West Nile virus (WNV) is a widely distributed enveloped flavivirus transmitted by mosquitoes, which main hosts are birds. The virus sporadically infects equids and humans with serious economic and health consequences, as infected individuals can develop a severe neuroinvasive disease that can even lead to death. Nowadays, no WNV-specific therapy is available and vaccines are only licensed for use in horses but not for humans. While several methodologies for WNV vaccine development have been successfully applied and have contributed to significantly reducing its incidence in horses in the US, none have progressed to phase III clinical trials in humans. This review addresses the status of WNV vaccines for horses, birds, and humans, summarizing and discussing the challenges they face for their clinical advance and their introduction to the market.
TaqMan Assays for Simultaneous Detection of Bacillus anthracis and Bacillus cereus biovar anthracis
Authors: Zincke Diansy , Norris Michael H. , Cruz Odalis , Kurmanov Berzhan , McGraw W. Scott , Daegling David J. , Krigbaum John , Hoang Thi Thu Ha , Khanipov Kamil , Golovko Georgiy , Hadfield Ted , Blackburn Jason K.
Published: December 2020

Anthrax is a worldwide zoonotic disease caused by the spore-forming bacterium Bacillus anthracis. Primarily a disease of herbivores, human infections often result from direct contact with contaminated animal products (cutaneous and inhalational anthrax) or through consumption of infected meat (gastrointestinal anthrax). The genetic near neighbor, Bacillus cereus biovar anthracis (Bcbva), causes an anthrax-like illness in the wildlife and livestock of west and central Africa due to the presence and expression of B. anthracis-specific virulence factors in this background. While Bcbva infections have not been reported in humans, a recent seroprevalence study detected Bcbva antibodies in the rural population around Taï National Park. This work describes the development of new TaqMan multiplex PCRs for the simultaneous detection of B. anthracis and Bcbva. The assays are designed to amplify Ba-1, capB, and lef markers in B. anthracis and genomic island IV (GI4), capB, and lef in Bcbva. Our assays allow for the rapid discrimination of B. anthracis and Bcbva and will provide insights into the molecular epidemiology of these two important pathogens that share an overlapping geographical range in west and central Africa.
A New Phage Lysin Isolated from the Oral Microbiome Targeting Streptococcus pneumoniae
Authors: van der Kamp Imme , Draper Lorraine A. , Smith Muireann K. , Buttimer Colin , Ross R. Paul , Hill Colin
Published: December 2020

Streptococcus pneumoniae is highly pathogenic and causes several mucosal and invasive infections. Due to the rising number of multidrug-resistant (MDR) strains of S. pneumoniae, new antimicrobials with alternative mechanisms of action are urgently needed. In this study, we identified two new Streptococcal phages from the oral microbiome, 23TH and SA01. Their lysins, 23TH_48 and SA01_53, were recombinantly expressed, characterized and tested for their lethality. SA01_53 was found to only lyse its host strain of S. anginosus, while 23TH_48 was found to possess a broader lytic activity beyond its host strain of S. infantis, with several S. pneumoniae isolates sensitive to its lytic activity. 23TH_48 at a concentration of five activity units per mL (U/mL) was found to reduce cell counts of S. pneumoniae DSM 24048 by 4 log10 colony forming units per mL (CFU/mL) within 1 h and effectively prevented and destroyed biofilms of S. pneumoniae R6 at concentrations of 228.8 ng/µL and 14.3 ng/µL, respectively. Given its high lytic activity, 23TH_48 could prove to be a promising candidate to help combat pneumococcal infections.
Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation
Authors: Sarango-Granda Paulo , Silva-Abreu Marcelle , Calpena Ana , Halbaut Lyda , Fábrega María-José , Rodríguez-Lagunas María , Díaz-Garrido Natalia , Badia Josefa , Espinoza Lupe
Published: December 2020

Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation.
Exploring the Anti-Cancer Mechanism of Novel 3,4′-Substituted Diaryl Guanidinium Derivatives
Authors: Previtali Viola , Mihigo Helene B. , Amet Rebecca , McElligott Anthony M. , Zisterer Daniela M. , Rozas Isabel
Published: December 2020

We previously identified a guanidinium-based lead compound that inhibited BRAF through a hypothetic type-III allosteric mechanism. Considering the pharmacophore identified in this lead compound (i.e., “lipophilic group”, “di-substituted guanidine”, “phenylguanidine polar end”), several modifications were investigated to improve its cytotoxicity in different cancer cell lines. Thus, several lipophilic groups were explored, the di-substituted guanidine was replaced by a secondary amine and the phenyl ring in the polar end was substituted by a pyridine. In a structure-based design approach, four representative derivatives were docked into an in-house model of an active triphosphate-containing BRAF protein, and the interactions established were analysed. Based on these computational studies, a variety of derivatives was synthesized, and their predicted drug-like properties calculated. Next, the effect on cell viability of these compounds was assessed in cell line models of promyelocytic leukaemia and breast, cervical and colorectal carcinomas. The potential of a selection of these compounds as apoptotic agents was assessed by screening in the promyelocytic leukaemia cell line HL-60. The toxicity against non-tumorigenic epithelial MCF10A cells was also investigated. These studies allowed for several structure-activity relationships to be derived. Investigations on the mechanism of action of representative compounds suggest a divergent effect on inhibition of the MAPK/ERK signalling pathway.
Biodegradable Nanoparticle for Cornea Drug Delivery: Focus Review
Authors: Mobaraki Mohammadmahdi , Soltani Madjid , Zare Harofte Samaneh , L. Zoudani Elham , Daliri Roshanak , Aghamirsalim Mohamadreza , Raahemifar Kaamran
Published: December 2020

During recent decades, researchers all around the world have focused on the characteristic pros and cons of the different drug delivery systems for cornea tissue change for sense organs. The delivery of various drugs for cornea tissue is one of the most attractive and challenging activities for researchers in biomaterials, pharmacology, and ophthalmology. This method is so important for cornea wound healing because of the controllable release rate and enhancement in drug bioavailability. It should be noted that the delivery of various kinds of drugs into the different parts of the eye, especially the cornea, is so difficult because of the unique anatomy and various barriers in the eye. Nanoparticles are investigated to improve drug delivery systems for corneal disease. Biodegradable nanocarriers for repeated corneal drug delivery is one of the most attractive and challenging methods for corneal drug delivery because they have shown acceptable ability for this purpose. On the other hand, by using these kinds of nanoparticles, a drug could reside in various part of the cornea for longer. In this review, we summarized all approaches for corneal drug delivery with emphasis on the biodegradable nanoparticles, such as liposomes, dendrimers, polymeric nanoparticles, niosomes, microemulsions, nanosuspensions, and hydrogels. Moreover, we discuss the anatomy of the cornea at first and gene therapy at the end.
Nanovesicle-Mediated Delivery Systems for CRISPR/Cas Genome Editing
Authors: Kim Dongyoon , Le Quoc-Viet , Wu Yina , Park Jinwon , Oh Yu-Kyoung
Published: December 2020

Genome-editing technology has emerged as a potential tool for treating incurable diseases for which few therapeutic modalities are available. In particular, discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system together with the design of single-guide RNAs (sgRNAs) has sparked medical applications of genome editing. Despite the great promise of the CRISPR/Cas system, its clinical application is limited, in large part, by the lack of adequate delivery technology. To overcome this limitation, researchers have investigated various systems, including viral and nonviral vectors, for delivery of CRISPR/Cas and sgRNA into cells. Among nonviral delivery systems that have been studied are nanovesicles based on lipids, polymers, peptides, and extracellular vesicles. These nanovesicles have been designed to increase the delivery of CRISPR/Cas and sgRNA through endosome escape or using various stimuli such as light, pH, and environmental features. This review covers the latest research trends in nonviral, nanovesicle-based delivery systems that are being applied to genome-editing technology and suggests directions for future progress.
Pharmacogenetic Testing: A Tool for Personalized Drug Therapy Optimization
Authors: Malsagova Kristina A. , Butkova Tatyana V. , Kopylov Arthur T. , Izotov Alexander A. , Potoldykova Natalia V. , Enikeev Dmitry V. , Grigoryan Vagarshak , Tarasov Alexander , Stepanov Alexander A. , Kaysheva Anna L.
Published: December 2020

Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician’s ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level.
An Investigation into the Relationship between Xanthan Gum Film Coating Materials and Predicted Oro-Esophageal Gliding Performance for Solid Oral Dosage Forms
Authors: Drumond Nélio , Stegemann Sven
Published: December 2020

Oral drug therapy is generally provided in the form of solid oral dosage forms (SODF) that have to be swallowed and move throughout the oro-esophageal system. Previous studies have provided evidence that the oro-esophageal transit of SODF depends on their shape, size, density, and surface characteristics. To estimate the impact of SODF surface coatings during esophageal transit, an in vitro system was implemented to investigate the gliding performance across an artificial mucous layer. In this work, formulations comprised of different slippery-inducing agents combined with a common film forming agent were evaluated using the artificial mucous layer system. Xanthan gum (XG) and polyethylene glycol 1500 (PEG) were applied as film-forming agents, while carnauba wax (CW), lecithin (LE), carrageenan (CA), gellan gum (GG) and sodium alginate (SA), and their combination with sodium lauryl sulfate (SLS), were applied as slippery-inducing components. All tested formulations presented lower static friction (SF) as compared to the negative control (uncoated disc, C, F0), whereas only CW/SLS-based formulations showed similar performance to F0 regarding dynamic friction (DF). The applied multivariate analysis approach allowed a higher level of detail to the evaluation and supported a better identification of excipients and respective concentrations that are predicted to improve in vivo swallowing safety.
Aqueous Extracts of Morus alba Root Bark and Cornus officinalis Fruit Protect against Osteoarthritis Symptoms in Testosterone-Deficient and Osteoarthritis-Induced Rats
Authors: Park Sunmin , Moon Bo Reum , Kim Ji Eun , Kim Hyun Joo , Zhang Ting
Published: December 2020

Water extracts of both Morus alba L. root bark (MBW) and Cornus officinalis Siebold and Zucc fruit (CFW) have traditionally been used to promote men’s health in the elderly in Asia. We determined that the 12-week consumption of MBW and CFW could alleviate testosterone-deficiency syndrome and osteoarthritis (OA) symptoms in testosterone-deficient rats, and the action mechanisms were explored. Rats with bilateral orchiectomy (ORX) were fed a 45% fat diet containing either 0.5% MBW (ORX-MBW), 0.5% CFW(ORX-CFW), or 0.5% dextrin (ORX-CON). Sham-operated rats also received 0.5% dextrin (Non-ORX-CON). After 8 weeks of treatment, all rats had an injection of monoiodoacetate (MIA) into the left knee, and they continued the same diet for the additional 4 weeks. ORX-CFW and ORX-MBW partially prevented the reduction of serum testosterone concentrations and decreased insulin resistance, compared to the ORX-CON. ORX-CFW and ORX-MBW protected against the reduction of bone mineral density (BMD) and lean body mass (LBM) compared to the ORX-CON. The limping and edema scores were lower in the order of the ORX-CON, ORX-CRF = ORX-MBW, and Non-ORX-CON (p < 0.05). The scores for pain behaviors, measured by weight-distribution on the OA leg and maximum running velocity on a treadmill, significantly decreased in the same order as limping scores. ORX-MBW protected against the increased expression of matrix metalloproteinase (MMP)-3 and MMP-13 and reduced the production of inflammatory markers such as TNF-α and IL-1β, by MIA in the articular cartilage, compared to the ORX-CON (p < 0.05). The cartilage damage near the tidemark of the knee and proteoglycan loss was significantly less in ORX-MBW than ORX-CON. In conclusion, MBW, possibly CFW, could be effective alternative therapeutic agents for preventing osteoarthritis in testosterone-deficient elderly men.
Electromagnetic Scattering Analysis of SHDB Objects Using Surface Integral Equation Method
Authors: Kong Beibei , Ylä-Oijala Pasi , Sihvola Ari
Published: December 2020

A surface integral equation (SIE) method is applied in order to analyze electromagnetic scattering by bounded arbitrarily shaped three-dimensional objects with the SHDB boundary condition. SHDB is a generalization of SH (Soft-and-Hard) and DB boundary conditions (at the DB boundary, the normal components of the D and B flux densities vanish). The SHDB boundary condition is a general linear boundary condition that contains two scalar equations that involve both the tangential and normal components of the electromagnetic fields. The multiplication of these scalar equations with two orthogonal vectors transforms them into a vector form that can be combined with the tangential field integral equations. The resulting equations are discretized and converted to a matrix equation with standard method of moments (MoM). As an example of use of the method, we investigate scattering by an SHDB circular disk and demonstrate that the SHDB boundary allows for an efficient way to control the polarization of the wave that is reflected from the surface. We also discuss perspectives into different levels of materialization and realization of SHDB boundaries.
Gibberellic Acid Modifies the Transcript Abundance of ABA Pathway Orthologs and Modulates Sweet Cherry (Prunus avium) Fruit Ripening in Early- and Mid-Season Varieties
Authors: Kuhn Nathalie , Ponce Claudio , Arellano Macarena , Time Alson , Sagredo Boris , Donoso José Manuel , Meisel Lee A.
Published: December 2020

Several phytohormones modulate ripening in non-climacteric fruits, which is triggered by abscisic acid (ABA). Gibberellins (GAs) are present during the onset of ripening in sweet cherry fruits, and exogenous gibberellic acid (GA3) application delays ripening, though this effect is variety-dependent. Although an ABA accumulation delay has been reported following GA3 treatment, the mechanism by which GA modulates this process has not been investigated at the molecular level in sweet cherry. Therefore, the aim of this work is to analyze the effect of GA3 on the fruit ripening process and the transcript levels of ABA pathway orthologs in two varieties having different maturity time phenotypes. The early-season variety had a rapid transition from yellow to pink fruit color, whereas pink color initiation took longer in the mid-season variety. GA3 increased the proportion of lighter colored fruits at ripeness in both varieties, but it produced a delay in IAD—a ripening index—only in the mid-season variety. This delay was accompanied by an increased transcript abundance of PavPP2Cs, which are putative negative regulators of the ABA pathway. On the other hand, the early-season variety had increased expression of PavCYP707A2—a putative ABA catabolic gene–, and reduced transcript levels of PavPP2Cs and SnRK2s after the GA3 treatment. Together these results show that GA modulates fruit ripening, exerting its action in part by interacting with the ABA pathway in sweet cherry.
Salinity-Induced Changes of Photosynthetic Performance, Lawsone, VOCs, and Antioxidant Metabolism in Lawsonia inermis L.
Authors: Najar Basma , Pistelli Laura , Marchioni Ilaria , Pistelli Luisa , Muscatello Beatrice , De Leo Marinella , Scartazza Andrea
Published: December 2020

The present study aimed to elucidate the salinity influence on the bioactive metabolites of Lawsonia inermis L. (henna) plants. Young henna plants were cultivated under salinity stress with two NaCl concentrations (75 mM and 150 mM) in controlled environmental conditions and the leaves were investigated to check their adaptative responses. The modulation of photosynthetic performance to salinity stress was demonstrated by gas exchange and chlorophyll fluorescence parameters. The partial stomatal closure triggered an enhanced water-use efficiency, and a proline accumulation was observed, leading to an osmotic adjustment. The increased capacity to dissipate the excess excitation energy at photosystem II as heat was associated with changes in chlorophylls, anthocyanins, and carotenoids. The higher antioxidant activity at 150 mM salt level suggested its scavenger role on reactive oxygen species (ROS) dissipation and photoprotection. The reduced CO2 uptake and the higher metabolic costs necessary to sustain the henna tolerance mechanism against high NaCl concentration negatively affected lawsone production. Leaf volatile organic compounds (VOCs) showed changes in the amount and composition of VOCs with increasing salinity level. Overall, this study revealed efficient physiological and biochemical adaptations of henna leaves to salt stress despite an altered production of important economic metabolites such as lawsone.
Identification, Characterization, and Stress Responsiveness of Glucose-6-phosphate Dehydrogenase Genes in Highland Barley
Authors: Feng Ruijun , Wang Xiaomin , He Li , Wang Shengwang , Li Junjie , Jin Jie , Bi Yurong
Published: December 2020

G6PDH provides intermediate metabolites and reducing power (nicotinamide adenine dinucleotide phosphate, NADPH) for plant metabolism, and plays a pivotal role in the cellular redox homeostasis. In this study, we cloned five G6PDH genes (HvG6PDH1 to HvG6PDH5) from highland barley and characterized their encoded proteins. Functional analysis of HvG6PDHs in E. coli showed that HvG6PDH1 to HvG6PDH5 encode the functional G6PDH proteins. Subcellular localization and phylogenetic analysis indicated that HvG6PDH2 and HvG6PDH5 are localized in the cytoplasm, while HvG6PDH1, HvG6PDH3, and HvG6PDH4 are plastidic isoforms. Analysis of enzymatic activities and gene expression showed that HvG6PDH1 to HvG6PDH4 are involved in responses to salt and drought stresses. The cytosolic HvG6PDH2 is the major isoform against oxidative stress. HvG6PDH5 may be a house-keeping gene. In addition, HvG6PDH1 to HvG6PDH4 and their encoded enzymes responded to jasmonic acid (JA) and abscisic acid (ABA) treatments, implying that JA and ABA are probably critical regulators of HvG6PDHs (except for HvG6PDH5). Reactive oxygen species analysis showed that inhibition of cytosolic and plastidic G6PDH activities leads to increased H2O2 and O2− contents in highland barley under salt and drought stresses. These results suggest that G6PDH can maintain cellular redox homeostasis and that cytosolic HvG6PDH2 is an irreplaceable isoform against oxidative stress in highland barley.
Physico-Chemical Characteristics and Culturable Microbial Communities of Grape Berries Change Strongly during Noble Rot Development
Authors: Hegyi-Kaló Júlia , Hegyi Ádám István , Geml József , Zsófi Zsolt , Pálfi Xénia , Váczy Kálmán Zoltán
Published: December 2020

Botrytis cinerea is a well-known pathogen of grapevine. However, under certain microclimatic conditions, Botrytis infection results in noble rot, an essential process in the production of the world-known Tokaji aszú wines in Hungary. We investigated the physico-chemical characteristics and culturable microorganisms associated with grape berries through several noble rot phases in the two main cultivars grown in Tokaj: Vitisvinifera cv. “Furmint” and “Hárslevelű”. We measured physical and analytical parameters routinely tested in viticulture and analyzed the ITS rDNA sequence data of fungi isolated from the sampled berries. We observed significant differences in the physico-chemical parameters among the noble rot phases as well as sampling dates. The greatest variation in berry texture and microbial structure was observed in the initial phases, with variables converging as the noble rot progressed. By finding a bijection between the examined chemical properties and the factorial parameters (e.g., noble rot phase, collection time, cultivar), an appropriate sweet winemaking material can be designed. Fungal community differed significantly among cultivars, with higher number of species observed in Hárslevelű. Our results reveal that there is more to noble rot than only Botrytiscinerea and other microorganisms may play important roles in the aszú process.
Biocompatibility and Cytotoxicity Study of Polydimethylsiloxane (PDMS) and Palm Oil Fuel Ash (POFA) Sustainable Super-Hydrophobic Coating for Biomedical Applications
Authors: Sreekantan Srimala , Hassan Mohd , Sundera Murthe Satisvar , Seeni Azman
Published: December 2020

A sustainable super-hydrophobic coating composed of silica from palm oil fuel ash (POFA) and polydimethylsiloxane (PDMS) was synthesised using isopropanol as a solvent and coated on a glass substrate. FESEM and AFM analyses were conducted to study the surface morphology of the coating. The super-hydrophobicity of the material was validated through goniometry, which showed a water contact angle of 151°. Cytotoxicity studies were conducted by assessing the cell viability and cell morphology of mouse fibroblast cell line (L929) and hamster lung fibroblast cell line (V79) via tetrazolium salt 3-(4–dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and microscopic methods, respectively. The clonogenic assay was performed on cell line V79 and the cell proliferation assay was performed on cell line L929. Both results validate that the toxicity of PDMS: SS coatings is dependent on the concentration of the super-hydrophobic coating. The results also indicate that concentrations above 12.5 mg/mL invariably leads to cell toxicity. These results conclusively support the possible utilisation of the synthesised super-hydrophobic coating for biomedical applications.