bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon Nanomaterials as Versatile Platforms for Biosensing Applications
Authors: Hwang Hye Suk , Jeong Jae Won , Kim Yoong Ahm , Chang Mincheol
Published: August 2020

A biosensor is defined as a measuring system that includes a biological receptor unit with distinctive specificities toward target analytes. Such analytes include a wide range of biological origins such as DNAs of bacteria or viruses, or proteins generated from an immune system of infected or contaminated living organisms. They further include simple molecules such as glucose, ions, and vitamins. One of the major challenges in biosensor development is achieving efficient signal capture of biological recognition-transduction events. Carbon nanomaterials (CNs) are promising candidates to improve the sensitivity of biosensors while attaining low detection limits owing to their capability of immobilizing large quantities of bioreceptor units at a reduced volume, and they can also act as a transduction element. In addition, CNs can be adapted to functionalization and conjugation with organic compounds or metallic nanoparticles; the creation of surface functional groups offers new properties (e.g., physical, chemical, mechanical, electrical, and optical properties) to the nanomaterials. Because of these intriguing features, CNs have been extensively employed in biosensor applications. In particular, carbon nanotubes (CNTs), nanodiamonds, graphene, and fullerenes serve as scaffolds for the immobilization of biomolecules at their surface and are also used as transducers for the conversion of signals associated with the recognition of biological analytes. Herein, we provide a comprehensive review on the synthesis of CNs and their potential application to biosensors. In addition, we discuss the efforts to improve the mechanical and electrical properties of biosensors by combining different CNs.
Characterization of Diabetic and Non-Diabetic Foot Ulcers Using Single-Cell RNA-Sequencing
Authors: Januszyk Michael , Chen Kellen , Henn Dominic , Foster Deshka S. , Borrelli Mimi R. , Bonham Clark A. , Sivaraj Dharshan , Wagh Dhananjay , Longaker Michael T. , Wan Derrick C. , Gurtner Geoffrey C.
Published: August 2020

Background: Recent advances in high-throughput single-cell sequencing technologies have led to their increasingly widespread adoption for clinical applications. However, challenges associated with tissue viability, cell yield, and delayed time-to-capture have created unique obstacles for data processing. Chronic wounds, in particular, represent some of the most difficult target specimens, due to the significant amount of fibrinous debris, extracellular matrix components, and non-viable cells inherent in tissue routinely obtained from debridement. Methods: Here, we examined the feasibility of single cell RNA sequencing (scRNA-seq) analysis to evaluate human chronic wound samples acquired in the clinic, subjected to prolonged cold ischemia time, and processed without FACS sorting. Wound tissue from human diabetic and non-diabetic plantar foot ulcers were evaluated using an optimized 10X Genomics scRNA-seq platform and analyzed using a modified data pipeline designed for low-yield specimens. Cell subtypes were identified informatically and their distributions and transcriptional programs were compared between diabetic and non-diabetic tissue. Results: 139,000 diabetic and non-diabetic wound cells were delivered for 10X capture after either 90 or 180 min of cold ischemia time. cDNA library concentrations were 858.7 and 364.7 pg/µL, respectively, prior to sequencing. Among all barcoded fragments, we found that 83.5% successfully aligned to the human transcriptome and 68% met the minimum cell viability threshold. The average mitochondrial mRNA fraction was 8.5% for diabetic cells and 6.6% for non-diabetic cells, correlating with differences in cold ischemia time. A total of 384 individual cells were of sufficient quality for subsequent analyses; from this cell pool, we identified transcriptionally-distinct cell clusters whose gene expression profiles corresponded to fibroblasts, keratinocytes, neutrophils, monocytes, and endothelial cells. Fibroblast subpopulations with differing fibrotic potentials were identified, and their distributions were found to be altered in diabetic vs. non-diabetic cells. Conclusions: scRNA-seq of clinical wound samples can be achieved using minor modifications to standard processing protocols and data analysis methods. This simple approach can capture widespread transcriptional differences between diabetic and non-diabetic tissue obtained from matched wound locations.
Enterotypes of the Gut Microbial Community and Their Response to Plant Secondary Compounds in Plateau Pikas
Authors: Fan Chao , Zhang Liangzhi , Fu Haibo , Liu Chuanfa , Li Wenjing , Cheng Qi , Zhang He , Jia Shangang , Zhang Yanming
Published: August 2020

Animal gut microbiomes can be clustered into “enterotypes” characterized by an abundance of signature genera. The characteristic determinants, stability, and resilience of these community clusters remain poorly understood. We used plateau pika (Ochotona curzoniae) as a model and identified three enterotypes by 16S rDNA sequencing. Among the top 15 genera, 13 showed significantly different levels of abundance between the enterotypes combined with different microbial functions and distinct fecal short-chain fatty acids. We monitored changes in the microbial community associated with the transfer of plateau pikas from field to laboratory and observed that feeding them a single diet reduced microbial diversity, resulting in a single enterotype with an altered composition of the dominant bacteria. However, microbial diversity, an abundance of some changed dominant genera, and enterotypes were partially restored after adding swainsonine (a plant secondary compound found in the natural diet of plateau pikas) to the feed. These results provide strong evidence that gut microbial diversity and enterotypes are directly related to specific diet, thereby indicating that the formation of different enterotypes can help animals adapt to complex food conditions. Additionally, natural plant secondary compounds can maintain dominant bacteria and inter-individual differences of gut microbiota and promote the resilience of enterotypes in small herbivorous mammals.
Automated Synthesis of Fluorine-18 Labeled CXCR4 Ligand via the Conjugation with Nicotinic Acid N-Hydroxysuccinimide Ester (6-[18F]SFPy)
Authors: Basuli Falguni , Zhang Xiang , Phelps Tim E. , Jagoda Elaine M. , Choyke Peter L. , Swenson Rolf E.
Published: August 2020

The C-X-C motif chemokine receptor 4 (CXCR4) is a seven-transmembrane G protein-coupled receptor that is overexpressed in numerous diseases, particularly in various cancers and is a powerful chemokine, attracting cells to the bone marrow niche. Therefore, CXCR4 is an attractive target for imaging and therapeutic purposes. The goal of this study is to develop an efficient, reproducible, and straightforward method to prepare a fluorine-18 labeled CXCR4 ligand. 6-[18F]Fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester (6-[18F]FPy-TFP) and nicotinic acid N-hydroxysuccinimide ester (6-[18F]SFPy) have been prepared using ‘fluorination on the Sep-Pak’ method. Conjugation of 6-[18F]SFPy or 6-[18F]FPy-TFP with the alpha-amino group at the N terminus of the protected T140 precursor followed by deprotection, yielded the final product 6-[18F]FPy-T140. The overall radiochemical yields were 6–17% (n = 15, decay-corrected) in a 90-min radiolabeling time with a radiochemical purity >99%. 6-[18F]FPy-T140 exhibited high specific binding and nanomolar affinity for CXCR4 in vitro, indicating that the biological activity of the peptide was preserved. For the first time, [18F]SFPy has been prepared using ‘fluorination on the Sep-Pak’ method that allows rapid automated synthesis of 6-[18F]FPy-T140. In addition to increased synthetic efficiency, this construct binds with CXCR4 in high affinity and may have potential as an in vivo positron emission tomography (PET) imaging agent. This radiosynthesis method should encourage wider use of this PET agent to quantify CXCR4 in both research and clinical settings.
Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives
Authors: Rzepiela Kacper , Buczek Aneta , Kupka Teobald , Broda Małgorzata A.
Published: August 2020

We report on the density functional theory (DFT) modelling of structural, energetic and NMR parameters of uracil and its derivatives (5-halogenouracil (5XU), X = F, Cl, Br and I) in vacuum and in water using the polarizable continuum model (PCM) and the solvent model density (SMD) approach. On the basis of the obtained results, we conclude that the intramolecular electrostatic interactions are the main factors governing the stability of the six tautomeric forms of uracil and 5XU. Two indices of aromaticity, the harmonic oscillator model of aromaticity (HOMA), satisfying the geometric criterion, and the nuclear independent chemical shift (NICS), were applied to evaluate the aromaticity of uracil and its derivatives in the gas phase and water. The values of these parameters showed that the most stable tautomer is the least aromatic. A good performance of newly designed xOPBE density functional in combination with both large aug-cc-pVQZ and small STO(1M)−3G basis sets for predicting chemical shifts of uracil and 5-fluorouracil in vacuum and water was observed. As a practical alternative for calculating the chemical shifts of challenging heterocyclic compounds, we also propose B3LYP calculations with small STO(1M)−3G basis set. The indirect spin–spin coupling constants predicted by B3LYP/aug-cc-pVQZ(mixed) method reproduce the experimental data for uracil and 5-fluorouracil well.
When Thermodynamic Properties of Adsorbed Films Depend on Size: Fundamental Theory and Case Study
Authors: Strøm Bjørn A. , He Jianying , Bedeaux Dick , Kjelstrup Signe
Published: August 2020

Small system properties are known to depend on geometric variables in ways that are insignificant for macroscopic systems. Small system considerations are therefore usually added to the conventional description as needed. This paper presents a thermodynamic analysis of adsorbed films of any size in a systematic and general way within the framework of Hill’s nanothermodynamics. Hill showed how to deal with size and shape as variables in a systematic manner. By doing this, the common thermodynamic equations for adsorption are changed. We derived the governing thermodynamic relations characteristic of adsorption in small systems, and point out the important distinctions between these and the corresponding conventional relations for macroscopic systems. We present operational versions of the relations specialized for adsorption of gas on colloid particles, and we applied them to analyze molecular simulation data. As an illustration of their use, we report results for CO2 adsorbed on graphite spheres. We focus on the spreading pressure, and the entropy and enthalpy of adsorption, and show how the intensive properties are affected by the size of the surface, a feature specific to small systems. The subdivision potential of the film is presented for the first time, as a measure of the film’s smallness. For the system chosen, it contributes with a substantial part to the film enthalpy. This work can be considered an extension and application of the nanothermodynamic theory developed by Hill. It provides a foundation for future thermodynamic analyses of size- and shape-dependent adsorbed film systems, alternative to that presented by Gibbs.
Anisotropic Photonics Topological Transition in Hyperbolic Metamaterials Based on Black Phosphorus
Authors: Su Zengping , Wang Yueke
Published: August 2020

Based on in-plane anisotropy of black phosphorus (BP), anisotropic photonics topological transition (PTT) can be achieved by the proposed hyperbolic metamaterials structure, which is composed of alternating BP/SiO2 multilayer. Through effective medium theory and calculated iso-frequency contour, PTT can be found by carefully choosing the incident plane and other parameters. With the finite element method and transfer matrix method, a narrow angular optical transparency window with angular full width at half maximum of 1.32° exists at PTT. By changing the working wavelength, thickness of SiO2, or electron doping of black phosphorus, the incident plane of realizing PTT can be modulated, and anisotropic PTT is achieved.
DNA Origami Nano-Sheets and Nano-Rods Alter the Orientational Order in a Lyotropic Chromonic Liquid Crystal
Authors: Zhang Bingru , Martens Kevin , Kneer Luisa , Funck Timon , Nguyen Linh , Berger Ricarda , Dass Mihir , Kempter Susanne , Schmidtke Jürgen , Liedl Tim , Kitzerow Heinz-S.
Published: August 2020

Rod-like and sheet-like nano-particles made of desoxyribonucleic acid (DNA) fabricated by the DNA origami method (base sequence-controlled self-organized folding of DNA) are dispersed in a lyotropic chromonic liquid crystal made of an aqueous solution of disodium cromoglycate. The respective liquid crystalline nanodispersions are doped with a dichroic fluorescent dye and their orientational order parameter is studied by means of polarized fluorescence spectroscopy. The presence of the nano-particles is found to slightly reduce the orientational order parameter of the nematic mesophase. Nano-rods with a large length/width ratio tend to preserve the orientational order, while more compact stiff nano-rods and especially nano-sheets reduce the order parameter to a larger extent. In spite of the difference between the sizes of the DNA nano-particles and the rod-like columnar aggregates forming the liquid crystal, a similarity between the shapes of the former and the latter seems to be better compatible with the orientational order of the liquid crystal.
Effects of Constant Magnetic Field to the Proliferation Rate of Human Fibroblasts Grown onto Different Substrates: Tissue Culture Polystyrene, Polyacrylamide Hydrogel and Ferrogels γ-Fe2O3 Magnetic Nanoparticles
Authors: Blyakhman Felix A. , Melnikov Grigory Yu. , Makarova Emilia B. , Fadeyev Fedor A. , Sedneva-Lugovets Daiana V. , Shabadrov Pavel A. , Volchkov Stanislav O. , Mekhdieva Kamiliya R. , Safronov Alexander P. , Fernández Armas Sergio , Kurlyandskaya Galina V.
Published: August 2020

The static magnetic field was shown to affect the proliferation, adhesion and differentiation of various types of cells, making it a helpful tool for regenerative medicine, though the mechanism of its impact on cells is not completely understood. In this work, we have designed and tested a magnetic system consisting of an equidistant set of the similar commercial permanent magnets (6 × 4 assay) in order to get insight on the potential of its experimental usage in the biological studies with cells culturing in a magnetic field. Human dermal fibroblasts, which are widely applied in regenerative medicine, were used for the comparative study of their proliferation rate on tissue culture polystyrene (TCPS) and on the polyacrylamide ferrogels with 0.00, 0.63 and 1.19 wt % concentrations of γ-Fe2O3 magnetic nanoparticles obtained by the well-established technique of laser target evaporation. We used either the same batch as in previously performed but different biological experiments or the same fabrication conditions for fabrication of the nanoparticles. This adds special value to the understanding of the mechanisms of nanoparticles contributions to the processes occurring in the living systems in their presence. The magnetic field increased human dermal fibroblast cell proliferation rate on TCPS, but, at the same time, it suppressed the growth of fibroblasts on blank gel and on polyacrylamide ferrogels. However, the proliferation rate of cells on ferrogels positively correlated with the concentration of nanoparticles. Such a dependence was observed both for cell proliferation without the application of the magnetic field and under the exposure to the constant magnetic field.
Paraburkholderia phymatum STM815 σ54 Controls Utilization of Dicarboxylates, Motility, and T6SS-b Expression
Authors: Lardi Martina , Liu Yilei , Hug Sebastian , Bolzan de Campos Samanta , Eberl Leo , Pessi Gabriella
Published: August 2020

Rhizobia have two major life styles, one as free-living bacteria in the soil, and the other as bacteroids within the root/stem nodules of host legumes where they convert atmospheric nitrogen into ammonia. In the soil, rhizobia have to cope with changing and sometimes stressful environmental conditions, such as nitrogen limitation. In the beta-rhizobial strain Paraburkholderia phymatum STM815, the alternative sigma factor σ54 (or RpoN) has recently been shown to control nitrogenase activity during symbiosis with Phaseolus vulgaris. In this study, we determined P. phymatum’s σ54 regulon under nitrogen-limited free-living conditions. Among the genes significantly downregulated in the absence of σ54, we found a C4-dicarboxylate carrier protein (Bphy_0225), a flagellar biosynthesis cluster (Bphy_2926-64), and one of the two type VI secretion systems (T6SS-b) present in the P. phymatum STM815 genome (Bphy_5978-97). A defined σ54 mutant was unable to grow on C4 dicarboxylates as sole carbon source and was less motile compared to the wild-type strain. Both defects could be complemented by introducing rpoNin trans. Using promoter reporter gene fusions, we also confirmed that the expression of the T6SS-b cluster is regulated by σ54. Accordingly, we show that σ54 affects in vitro competitiveness of P. phymatum STM815 against Paraburkholderia diazotrophica.
Inhibitory Effects of a Sargassum miyabei Yendo on Cutibacterium acnes-Induced Skin Inflammation
Authors: Yim Mi-Jin , Lee Jeong Min , Kim Hyun-Soo , Choi Grace , Kim Young-Mog , Lee Dae-Sung , Choi Il-Whan
Published: August 2020

Acne vulgaris is a chronic inflammatory condition of skin sebaceous follicles. To explore its effects on acne vulgaris, we investigated the antibacterial and anti-inflammatory activities of Sargassum miyabei Yendo (a brown alga) ethanolic extract (SMYEE) on Cutibacterium acnes (C. acnes)-stimulated inflammatory responses, both in vivo and in vitro. To induce inflammation in vivo, C. acnes was intradermally injected into the dorsal skin of mice, to which SMYEE was applied. The antimicrobial activity of SMYEE was evaluated by the determination of minimum inhibitory concentrations (MICs). To explore in vitro anti-inflammatory effects, HaCaT cells were stimulated with C. acnes after treatment with SMYEE. The levels of IL-8 and the underlying molecular effects in C. acnes-stimulated HaCaT cells were assessed by enzyme-linked immunosorbent assay, Western blotting, and an electrophoretic mobility shift assay. Mouse skin lesions improved after treatment with SMYEE (50 μg/mouse). Neutrophil infiltration was significantly reduced in SMYEE-treated compared to SMYEE-untreated skin lesions. SMYEE reversed the C. acnes-induced increase in IL-8 levels in HaCaT cells and suppressed dHL-60 cell migration. SMYEE also inhibited C. acnes-induced phosphorylation of the extracellular signal-regulated kinase and inhibited activator protein-1 signaling. SMYEE may be a useful treatment for C. acnes-induced acne vulgaris.
Can the FUT 2 Gene Variant Have an Effect on the Body Weight of Patients Undergoing Bariatric Surgery?—Preliminary, Exploratory Study
Authors: Komorniak Natalia , Martynova-Van Kley Alexandra , Nalian Armen , Wardziukiewicz Wiktoria , Skonieczna-Żydecka Karolina , Styburski Daniel , Palma Joanna , Kowalewski Bartosz , Kaseja Krzysztof , Stachowska Ewa
Published: August 2020

Background: The FUT2 gene (Se gene) encoding the enzyme α-1,2-L-fucosyltransferase 2 seems to have a significant effect on the number and type of bacteria colonizing the intestines. Methods: In a group of 19 patients after bariatric surgery, the polymorphism (rs601338) of FUT2 gene was analyzed in combination with body mass reduction, intestinal microbiome (16S RNA sequencing), and short chain fatty acids (SCFA) measurements in stools. Results: Among the secretors (Se/Se polymorphism of the FUT2 gene rs601338, carriers of GG variant), correlations between waist-hip ratio (WHR) and propionate content and an increase in Prevotella, Escherichia, Shigella, and Bacteroides were observed. On the other hand—in non-secretors (carriers of GA and AA variants)—higher abundance of Enterobacteriaceae, Ruminococcaceae, Enterobacteriaceae, Clostridiales was recorded. Conclusions: The increased concentrations of propionate observed among the GG variants of FUT 2 may be used as an additional source of energy for the patient and may have a higher risk of increasing the WHR than carriers of the other variants (GA and AA).
A High Phosphorus Diet Impairs Testicular Function and Spermatogenesis in Male Mice with Chronic Kidney Disease
Authors: Tsao Chih-Wei , Hsu Yu-Juei , Chang Ting-Chia , Wu Sheng-Tang , Cha Tai-Lung , Liu Chin-Yu
Published: August 2020

Hyperphosphatemia is a serious complication in chronic kidney disease (CKD) that occurs due to insufficient excretion of phosphorus during failure of renal function. Both CKD and an excessive phosphorus intake have been reported to increase oxidative stress and result in poor male fertility, but little is known about the reproductive function of the CKD under a poorly controlled phosphate intake. Eight-week-old C57BL/6 mice (n = 66) were randomly divided into four groups: a sham operation group received a chow diet as control (SC group, n = 14), CKD-induced mice received a chow diet (CKDC group, n = 16), control mice received a high phosphorus (HP) diet (SP group, n = 16), and CKD-induced mice received a HP diet (CKDP group, n = 20). CKD was induced by performing a 5/6 nephrectomy. The chow diet contained 0.6% phosphorus, while the HP diet contained 2% phosphorus. Impaired testicular function and semen quality found in the CKD model may result from increased oxidative stress, causing apoptosis and inflammation. The HP diet aggravated the negative effects of testicular damage in the CKD-induced mice.
Magnesium Levels Modify the Effect of Lipid Parameters on Carotid Intima Media Thickness
Authors: Cambray Serafi , Ibarz Merce , Bermudez-Lopez Marcelino , Marti-Antonio Manuel , Bozic Milica , Fernandez Elvira , Valdivielso Jose M.
Published: August 2020

Classical risk factors of atherosclerosis in the general population show paradoxical effects in chronic kidney disease (CKD) patients. Thus, low low-density lipoprotein (LDL) cholesterol levels have been associated with worse cardiovascular outcomes. Magnesium (Mg) is a divalent cation whose homeostasis is altered in CKD. Furthermore, Mg levels have been associated with cardiovascular health. The present study aims to understand the relationships of Mg and lipid parameters with atherosclerosis in CKD. In this analysis, 1754 participants from the Observatorio Nacional de Atherosclerosis en Nefrologia (NEFRONA) cohort were included. Carotid intima media thickness (cIMT) was determined in six arterial territories, and associated factors were investigated by linear regression. cIMT correlated positively with being male, Caucasian, a smoker, diabetic, hypertensive, dyslipidemic and with increased age, BMI, and triglyceride levels, and negatively with levels of HDL cholesterol. First-order interactions in linear regression analysis showed that Mg was an effect modifier on the influence of lipidic parameters. Thus, cIMT predicted values were higher when triglycerides or LDL levels were high and Mg levels were low. On the contrary, when Mg levels were high, this effect disappeared. In conclusion, Mg acts as an effect modifier between lipidic parameters and atherosclerotic cardiovascular disease. Therefore, Mg levels, together with lipidic parameters, should be taken into account when assessing atherosclerotic risk.
Entrapment of Citrus limon var. pompia Essential Oil or Pure Citral in Liposomes Tailored as Mouthwash for the Treatment of Oral Cavity Diseases
Authors: Palmas Lucia , Aroffu Matteo , Petretto Giacomo L. , Escribano-Ferrer Elvira , Díez-Sales Octavio , Usach Iris , Peris José-Esteban , Marongiu Francesca , Ghavam Mansureh , Fais Sara , Orrù Germano , Rached Rita Abi , Manca Maria Letizia , Manconi Maria
Published: August 2020

This work aimed at developing a mouthwash based on liposomes loading Citrus limon var. pompia essential oil or citral to treat oropharyngeal diseases. Vesicles were prepared by dispersing phosphatidylcholine and pompia essential oil or citral at increasing amounts (12, 25 and 50 mg/mL) in water. Transparent vesicle dispersions were obtained by direct sonication avoiding the use of organic solvents. Cryogenic transmission electron microscopy (cryo-TEM) confirmed the formation of unilamellar, spherical and regularly shaped vesicles. Essential oil and citral loaded liposomes were small in size (~110 and ~100 nm, respectively) and negatively charged. Liposomes, especially those loading citral, were highly stable as their physico-chemical properties did not change during storage. The formulations were highly biocompatible against keratinocytes, were able to counteract the damages induced in cells by using hydrogen peroxide, and able to increase the rate of skin repair. In addition, liposomes loading citral at higher concentrations inhibited the proliferation of cariogenic bacterium.
Recent Advances Regarding the Therapeutic Potential of Adapalene
Authors: Rusu Aura , Tanase Corneliu , Pascu Georgiana-Andreea , Todoran Nicoleta
Published: August 2020

Adapalene (ADP) is a representative of the third retinoids generation and successfully used in first-line acne treatment. ADP binds to retinoic acid nuclear receptors. The comedolytic, anti-inflammatory, antiproliferative, and immunomodulatory are the known ADP effects. Its safety profile is an advantage over other retinoids. ADP recently was found to be effective in the treatment of several dermatological diseases and photoaging besides the utility in the treatment of acne vulgaris. New biological effects of adapalene with therapeutic potential are highlighted in this review paper. Thus, adapalene could be a valuable therapeutic drug into the treatment of several types of cancer. Additionally, some neurodegenerative diseases could be treated with a suitable formulation for intravenous administration. The antibacterial activity against methicillin-resistant Staphylococcus aureus of an analogue of ADP has been proven. In different therapeutic schemes, ADP is more effective in combination with other active substances. New topical combinations with adapalene include ketoconazole (antifungal), mometasone furoate (anti-inflammatory corticosteroid), nadifloxacin (fluoroquinolone), and alfa and beta hydroxy acids. Combination with oral drugs is a new trend that enhances the properties of topical formulations with adapalene. Several studies have investigated the effects of ADP in co-administration with azithromycin, doxycycline, faropenem, isotretinoin, and valganciclovir. Innovative formulations of ADP also aim to achieve a better bioavailability, increased efficacy, and reduced side effects. In this review, we have highlighted the current studies on adapalene regarding biological effects useful in various treatment types. Adapalene has not been exploited yet to its full biological potential.
Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells
Authors: Jeong Yun Soo , Lam Thuy Giang , Jeong Seho , Ahn Sang-Gun
Published: August 2020

Multidrug resistance is a significant clinical crisis in cancer treatment and has been linked to the cellular expression of multidrug efflux transporters. The aim of this study was to examine the effects and mechanisms of the metformin derivative HL156A on human multidrug resistance (MDR) cancer cells. Here, HL156A significantly suppressed cell growth and colony formation through G2/M phase cell cycle arrest in MDR cancer cells. HL156A also reduced the wound closure rate and cell migration and induced caspase-3-dependent apoptosis. We found that HL156A inhibited the expression of MDR1 by inhibiting the HOXC6-mediated ERK1/2 signaling pathway and increased the sensitivity to paclitaxel or doxorubicin in MDR cells. Furthermore, HL156A significantly inhibited angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These results suggest the potential of the metformin derivative HL156A as a candidate therapeutic modality for the treatment of human multidrug-resistant cancers.
Enhanced Loading Efficiency and Mucoadhesion Properties of Gellan Gum Thin Films by Complexation with Hydroxypropyl-β-Cyclodextrin
Authors: Adrover Alessandra , di Muzio Laura , Trilli Jordan , Brandelli Chiara , Paolicelli Patrizia , Petralito Stefania , Casadei Maria Antonietta
Published: August 2020

Polymeric oral thin films (OTFs) were prepared by the casting method, combining gellan gum (GG), a water-soluble polysaccharide, and glycerol (Gly) as a plasticizing agent. GG-Gly films were investigated as potential systems for buccal drug delivery using fluconazole (Class I of the Biopharmaceutical Classification System) as a model drug. At a low concentration of Gly drug precipitation occurred while, for higher concentrations of Gly, a significant deterioration of mucoadhesive and mechanical properties was observed. One possible way to overcome all these problems could be the addition of hydroxypropyl-β-cyclodextrin (HP-β-CD) to the GG-Gly formulation as a drug-precipitation inhibitor. In this work the effect of cyclodextrin addition on the mechanical, mucoadhesive, swelling and release properties of GG-Gly films was investigated. In-vitro drug release studies were carried out using the paddle type dissolution apparatus (USP II) and the millifluidic flow-through device (MFTD). A moving-boundary model for swelling dynamics and release in USP II is proposed to estimate the effective diffusivity of the solvent, HP-β-CD, fluconazole and complex fluconazole/HP-β-CD in the swelling film. Experimental results, supported by theoretical modeling, confirmed that gellan gum-low glycerol thin films including HP-β-CD represent a suitable formulation for fluconazole drug delivery. A sustained release was observed when GG-Gly film is loaded with a preformed complex fluconazole/HP-β-CD.
Silver Nanomaterials for Wound Dressing Applications
Authors: Krishnan Priya Dharshini , Banas Dominik , Durai Ramya Devi , Kabanov Daniil , Hosnedlova Bozena , Kepinska Marta , Fernandez Carlos , Ruttkay-Nedecky Branislav , Nguyen Hoai Viet , Farid Awais , Sochor Jiri , Narayanan Vedha Hari B. , Kizek Rene
Published: August 2020

Silver nanoparticles (AgNPs) have recently become very attractive for the scientific community due to their broad spectrum of applications in the biomedical field. The main advantages of AgNPs include a simple method of synthesis, a simple way to change their morphology and high surface area to volume ratio. Much research has been carried out over the years to evaluate their possible effectivity against microbial organisms. The most important factors which influence the effectivity of AgNPs against microorganisms are the method of their preparation and the type of application. When incorporated into fabric wound dressings and other textiles, AgNPs have shown significant antibacterial activity against both Gram-positive and Gram-negative bacteria and inhibited biofilm formation. In this review, the different routes of synthesizing AgNPs with controlled size and geometry including chemical, green, irradiation and thermal synthesis, as well as the different types of application of AgNPs for wound dressings such as membrane immobilization, topical application, preparation of nanofibers and hydrogels, and the mechanism behind their antimicrobial activity, have been discussed elaborately.
Reply to “Comment on Casiraghi et al. ‘Mucoadhesive Budesonide Formulation for the Treatment of Eosinophilic Esophagitis’ 2020, 12, 211”
Authors: Casiraghi Antonella , Gennari Chiara Grazia , Musazzi Umberto Maria , Ortenzi Marco Aldo , Bordignon Susanna , Minghetti Paola
Published: August 2020

The paper entitled “Mucoadhesive Budesonide Formulation for the Treatment of Eosinophilic Esophagitis Pharmaceutics 2020, 12, 211” discusses the physicochemical and technological characterization of a formulation to treat eosinophilic esophagitis [...]
In Vivo Validation of Spray-Dried Mesoporous Bioactive Glass Microspheres Acting as Prolonged Local Release Systems for BMP-2 to Support Bone Regeneration
Authors: Berkmann Julia C. , Herrera Martin Aaron X. , Pontremoli Carlotta , Zheng Kai , Bucher Christian H. , Ellinghaus Agnes , Boccaccini Aldo R. , Fiorilli Sonia , Vitale Brovarone Chiara , Duda Georg N. , Schmidt-Bleek Katharina
Published: August 2020

Bone morphogenetic protein-2 (BMP-2) is a known key mediator of physiological bone regeneration and is clinically approved for selected musculoskeletal interventions. Yet, broad usage of this growth factor is impeded due to side effects that are majorly evoked by high dosages and burst release kinetics. In this study, mesoporous bioactive glass microspheres (MBGs), produced by an aerosol-assisted spray-drying scalable process, were loaded with BMP-2 resulting in prolonged, low-dose BMP-2 release without affecting the material characteristics. In vitro, MBGs were found to be cytocompatible and to induce a pro-osteogenic response in primary human mesenchymal stromal cells (MSCs). In a pre-clinical rodent model, BMP-2 loaded MBGs significantly enhanced bone formation and influenced the microarchitecture of newly formed bone. The MBG carriers alone performed equal to the untreated (empty) control in most parameters tested, while additionally exerting mild pro-angiogenic effects. Using MBGs as a biocompatible, pro-regenerative carrier for local and sustained low dose BMP-2 release could limit side effects, thus enabling a safer usage of BMP-2 as a potent pro-osteogenic growth factor.
Seed Dormancy Breaking and Germination in Bituminaria basaltica and B. bituminosa (Fabaceae)
Authors: Carruggio Francesca , Onofri Andrea , Impelluso Carmen , Giusso del Galdo Gianpietro , Scopece Giovanni , Cristaudo Antonia
Published: August 2020

Most legumes are well-known for the physical dormancy of their seeds; hence, the implementation of appropriate scarification techniques is essential for introducing new legume crops within agricultural systems. This study investigated morpho-anatomical traits and dormancy-breaking requirements in two taxa of the genus Bituminaria: the widespread B. bituminosa and the point endemic B. basaltica. As the species under investigation show monospermic indehiscent legumes, pods were used in this research. We performed pod trait measurements, light microscopy observations on the seed coat anatomical structure, and germination tests after mechanical, thermal, and chemical scarification treatments for seed dormancy breaking. Moreover, germination performance at different pod maturity stages and storage times was tested. Differences in morpho-anatomical traits were found, with B. basaltica having a thicker palisade cell layer and B. bituminosa showing larger pods. All of the scarification treatments proved to be able to break physical dormancy, with mechanical and chemical scarification being the most effective methods in both species. Nevertheless, dormancy-breaking treatments performed better in B. bituminosa. Seeds at early pod maturity stages showed higher germination capacity in both species. Overall, this research provided background knowledge on seed collection time, storage strategy, and effective pre-sowing treatment, which might contribute to enhance propagation and use of Bituminaria species for multiple purposes. Under this perspective, the future characterization of additional Bituminaria genetic resources from other Mediterranean populations will have remarkable importance.
Comparative Genomics and Phylogenetic Analyses of Christia vespertilionis and Urariopsis brevissima in the Tribe Desmodieae (Fabaceae: Papilionoideae) Based on Complete Chloroplast Genomes
Authors: Zhao Xue-Li , Zhu Zhang-Ming
Published: August 2020

Taxonomic and phylogenetic relationships of Christia, Urariopsis, Uraria and related genera within the tribe Desmodieae (Fabaceae: Papilionoideae) have long been controversial. Here, we report the complete chloroplast (cp) genomes of Christia vespertilionis and Urariopsis brevissima and perform comparative and phylogenetic analyses with Uraria lagopodioides and other relatives in the Desmodieae. The cp genomes of C. vespertilionis and U. brevissima are 149,656 and 149,930 bp long, with 128 unique genes (83 protein-coding genes, 37 tRNA genes and 8 rRNA genes), respectively. Comparative analyses revealed 95-129 simple sequence repeats (SSRs) and eleven highly variable regions (trnK-rbcL, rbcL-atpB, ndhJ-trnF, trnL-trnT, psbD-rpoB, accD-cemA, petA-psbL, psbE-petL, rps11-rps19, ndhF-ccsA, and rps15-ycf1) among six Desmodieae species. Phylogenetic analyses clearly resolved two subtribes (Desmodiinae and Lespedezinae) of Desmodieae as monophyletic, and the newly reported C. vespertilionis and U. brevissima clustered in subtribe Desmodiinae. A sister relationship of C. vespertilionis to U. lagopodioides was supported. Evidence was presented to support the treatment of Urariopsis as a distinct genus rather than in synonymy with Uraria. The results provide valuable information for further studies on species delimitation, phylogenetics, population genetics, and the evolutionary process of speciation in the Desmodieae.
A Modified 3D-QSAR Model Based on Ideal Point Method and Its Application in the Molecular Modification of Plasticizers with Flame Retardancy and Eco-Friendliness
Authors: Zhang Haigang , Zhao Chengji , Na Hui
Published: August 2020

The addition of plasticizers makes plastics flammable, and thus, poses a potential risk to the environment. In previous researches, plasticizers with flame retardancy had been synthesized, but their eco-friendliness had not been tested or described. Thus, in this paper, eco-friendliness plasticizers with flame retardancy were designed based on phthalic acid esters (PAEs), which are known as common plasticizers and major plastic additives. For a comprehensive analysis, such as flammability, biotoxicity, and enrichment effects, 17 PAEs’ comprehensive evaluation values were calculated based on the ideal point method. Further, a multi-effect three-dimensional quantitative structure-activity relationship (3D-QSAR) model of PAEs’ flammability, biotoxicity and enrichment effects was constructed. Thus, 18 dimethyl phthalate (DMP) derivatives and 20 diallyl phthalate (DAP) derivatives were designed based on three-dimensional contour maps. Through evaluation of eco-friendliness and flammability, six eco-friendly PAE derivatives with flame retardancy were screened out. Based on contour maps analysis, it was confirmed that the introduction of large groups and hydrophobic groups was beneficial to the simultaneous improvement of PAEs’ comprehensive effects, and multiple effects. In addition, the group properties were correlated significantly with improved degrees of the comprehensive effects of corresponding PAE derivatives, confirming the feasibility of the comprehensive evaluation method and modified scheme.
Anatase Incorporation to Bioactive Scaffolds Based on Salmon Gelatin and Its Effects on Muscle Cell Growth
Authors: Acevedo Cristian A. , Olguín Yusser , Orellana Nicole , Sánchez Elizabeth , Pepczynska Marzena , Enrione Javier
Published: August 2020

The development of new polymer scaffolds is essential for tissue engineering and for culturing cells. The use of non-mammalian bioactive components to formulate these materials is an emerging field. In our previous work, a scaffold based on salmon gelatin was developed and tested in animal models to regenerate tissues effectively and safely. Here, the incorporation of anatase nanoparticles into this scaffold was formulated, studying the new composite structure by scanning electron microscopy, differential scanning calorimetry and dynamic mechanical analysis. The incorporation of anatase nanoparticles modified the scaffold microstructure by increasing the pore size from 208 to 239 µm and significantly changing the pore shape. The glass transition temperature changed from 46.9 to 55.8 °C, and an increase in the elastic modulus from 79.5 to 537.8 kPa was observed. The biocompatibility of the scaffolds was tested using C2C12 myoblasts, modulating their attachment and growth. The anatase nanoparticles modified the stiffness of the material, making it possible to increase the growth of myoblasts cultured onto scaffolds, which envisions their use in muscle tissue engineering.
Multi Self-Healable UV Shielding Polyurethane/CeO2 Protective Coating: The Effect of Low-Molecular-Weight Polyols
Authors: Rahman Mohammad Mizanur , Suleiman Rami , Zahir Md. Hasan , Helal Aasif , Kumar A. Madhan , Haq Md. Bashirul
Published: August 2020

We prepared a series of polyurethane (PU) coatings with defined contents using poly(tetramethylene oxide)glycol (PTMG) with two different molecular weights (i.e., Mn = 2000 and 650), as well as polydimethyl siloxane (PDMS) with a molecular weight of Mn 550. For every coating, maximum adhesive strength and excellent self-healing character (three times) were found using 6.775 mol% mixed with low-molecular-weight-based polyols (PU-11-3-3). Defined 1.0 wt% CeO2 was also used for the PU-11-3-3 coating (i.e., PU-11-3-3-CeO2) to obtain UV shielding properties. Both the in situ polymerization and blending processes were separately applied during the preparation of the PU-11-3-3-CeO2 coating dispersion. The in situ polymerization-based coating (i.e., PU-11-3-3-CeO2-P) showed similar self-healing properties. The PU-11-3-3-CeO2-P coating also showed excellent UV shielding in real outdoor exposure conditions.
Layer-By-Layer Assemblies of Biopolymers: Build-Up, Mechanical Stability and Molecular Dynamics
Authors: Campbell Jack , Vikulina Anna S.
Published: August 2020

Rapid development of versatile layer-by-layer technology has resulted in important breakthroughs in the understanding of the nature of molecular interactions in multilayer assemblies made of polyelectrolytes. Nowadays, polyelectrolyte multilayers (PEM) are considered to be non-equilibrium and highly dynamic structures. High interest in biomedical applications of PEMs has attracted attention to PEMs made of biopolymers. Recent studies suggest that biopolymer dynamics determines the fate and the properties of such PEMs; however, deciphering, predicting and controlling the dynamics of polymers remains a challenge. This review brings together the up-to-date knowledge of the role of molecular dynamics in multilayers assembled from biopolymers. We discuss how molecular dynamics determines the properties of these PEMs from the nano to the macro scale, focusing on its role in PEM formation and non-enzymatic degradation. We summarize the factors allowing the control of molecular dynamics within PEMs, and therefore to tailor polymer multilayers on demand.
Polyimide-Based Nanocomposites with Binary CeO2/Nanocarbon Fillers: Conjointly Enhanced Thermal and Mechanical Properties
Authors: Nikolaeva Alexandra L. , Gofman Iosif V. , Yakimansky Alexander V. , Ivan’kova Elena M. , Abalov Ivan V. , Baranchikov Alexander E. , Ivanov Vladimir K.
Published: August 2020

To design novel polymer materials with optimal properties relevant to industrial usage, it would seem logical to modify polymers with reportedly good functionality, such as polyimides (PIs). We have created a set of PI-based nanocomposites containing binary blends of CeO2 with carbon nanoparticles (nanocones/discs or nanofibres), to improve a number of functional characteristics of the PIs. The prime novelty of this study is in a search for a synergistic effect amidst the nanofiller moieties regarding the thermal and the mechanical properties of PIs. In this paper, we report on the structure, thermal, and mechanical characteristics of the PI-based nanocomposites with binary fillers. We have found that, with a certain composition, the functional performance of a material can be substantially improved. For example, a PI containing SO2-groups in its macrochains not only had its thermal stability enhanced (by ~20 °C, 10% weight loss up to 533 °C) but also had its stiffness increased by more than 10% (Young’s modulus as high as 2.9–3.0 GPa) in comparison with the matrix PI. In the case of a PI with no sulfonic groups, binary fillers increased stiffness of the polymer above its glass transition temperature, thereby widening its working temperature range. The mechanisms of these phenomena are discussed. Thus, this study could contribute to the design of new composite materials with controllable and improved functionality.
On Complex Coacervate Core Micelles: Structure-Function Perspectives
Authors: Magana Jose Rodrigo , Sproncken Christian C. M. , Voets Ilja K.
Published: August 2020

The co-assembly of ionic-neutral block copolymers with oppositely charged species produces nanometric colloidal complexes, known, among other names, as complex coacervates core micelles (C3Ms). C3Ms are of widespread interest in nanomedicine for controlled delivery and release, whilst research activity into other application areas, such as gelation, catalysis, nanoparticle synthesis, and sensing, is increasing. In this review, we discuss recent studies on the functional roles that C3Ms can fulfil in these and other fields, focusing on emerging structure–function relations and remaining knowledge gaps.
A Laboratory Approach on the Hybrid-Enhanced Oil Recovery Techniques with Different Saline Brines in Sandstone Reservoirs
Authors: Hu Yisheng , Cheng Qiurong , Yang Jinping , Zhang Lifeng , Davarpanah Afshin
Published: August 2020

As foams are not thermodynamically stable and might be collapsed, foam stability is defined by interfacial properties and bulk solution. In this paper, we investigated foam injection and different salinity brines such as NaCl, CaCl2, KCl, and MgCl2 to measure cumulative oil production. According to the results of this experiment, it is concluded that sequential low-salinity water injections with KCl and foam flooding have provided the highest cumulative oil production in sandstone reservoirs. This issue is related to high wettability changes that had been caused by the KCl. As K+ is a monovalent cation, KCl has the highest wettability changes compared to other saline brines and formation water at 1000 ppm, which is due to the higher wettability changes of potassium (K+) over other saline ions. The interfacial tension for KCl at the lowest value is 1000 ppm and, for MgCl2, has the highest value in this concentration. Moreover, the formation brine, regarding its high value of salty components, had provided lower cumulative oil production before and after foam injection as it had mobilized more in the high permeable zones and, therefore, large volumes of oil would be trapped in the small permeable zones. This was caused by the low wettability alteration of the formation brine. Thereby, formation water flowed in large pores and the oil phase remained in small pores and channels. On the other hand, as foams played a significant role in the mobility control and sweep efficiency, at 2 pore volume, foam increased the pressure drop dramatically after brine injection. Consequently, foam injection after KCl brine injection had the maximum oil recovery factor of 63.14%. MgCl2 and formation brine had 41.21% and 36.51% oil recovery factor.