bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineralogical-Petrographic and Physical-Mechanical Features of the Construction Stones in Punic and Roman Temples of Antas (SW Sardinia, Italy): Provenance of the Raw Materials and Conservation State
Authors: Columbu Stefano , Gaviano Emanuela , Costamagna Luca Giacomo , Fancello Dario
Published: September 2021

The Antas site (SW Sardinia, Italy) is of fundamental cultural importance because it testifies the presence of Nuragic, Punic and Roman civilizations from the second millennium to the third century BC. This work focuses on the Punic and the Roman temples and aims to define their conservation state and provenance of construction materials through their minero-petrographic and physical-mechanical characterization. In addition, artificial geomaterials used in restoration works comprising a partial anastylosis and a consolidation intervention on the monument, were investigated to evaluate the aesthetic, petrographic and petrophysical compatibility with the original materials. The results indicate that Punic builders preferred to use a porous sandstone coming from at least few kilometres away from the site. By contrast, Roman builders opted for the use of the less porous and harder local metadolostones, more difficult to quarry and to hew but promptly available in the surrounding area. The Roman temple still preserves decorative architectural elements (as the Pronao threshold and the mosaic tesserae) whose source is definitely not local, suggesting the import of these materials. As regards artificial materials, a new material was found within the Punic temple consisting of a sandstone-like rock (i.e., lime based sandy-conglomeratic geomaterial) and characterized by higher mechanical strength and lower porosity.
Pesticides: Behavior in Agricultural Soil and Plants
Authors: Bondareva Lydia , Fedorova Nataliia
Published: September 2021

This review considers potential approaches to solve an important problem concerning the impact of applied pesticides of various classes on living organisms, mainly agricultural crops used as food. We used the method of multi-residual determination of several pesticides in agricultural food products with its practical application for estimating pesticides in real products and in model experiments. The distribution of the pesticide between the components of the soil-plant system was studied with a pesticide of the sulfonylureas class, i.e., rimsulfuron. Autoradiography showed that rimsulfuron inhibits the development of plants considered as weeds. Cereals are less susceptible to the effects of pesticides such as acetamiprid, flumetsulam and florasulam, while the development of legume shoots was inhibited with subsequent plant death.
A Novel Synthetic Precursor of Styryl Sulfone Neuroprotective Agents Inhibits Neuroinflammatory Responses and Oxidative Stress Damage through the P38 Signaling Pathway in the Cell and Animal Model of Parkinson’s Disease
Authors: Guo Ying , Ma Zhizhong , Ning Xianling , Chen Ying , Tian Chao , Wang Xiaowei , Zhang Zhili , Liu Junyi
Published: September 2021

A novel class of styryl sulfones were designed and synthesized as CAPE derivatives by our work team, which showed a multi-target neuroprotective effect, including antioxidative and anti-neuroinflammatory properties. However, the underlying mechanisms remain unclear. In the present study, the anti-Parkinson’s disease (PD) activity of 10 novel styryl sulfone compounds was screened by the cell viability test and the NO inhibition test in vitro. It was found that 4d exhibited the highest activity against PD among them. In a MPTP-induced mouse model of PD, the biological activity of 4d was validated through suppressing dopamine neurotoxicity, microglial activation, and astrocytes activation. With compound 4d, we conducted the mechanistic studies about anti-inflammatory responses through inhibition of p38 phosphorylation to protect dopaminergic neurons, and antioxidant effects through promoting nuclear factor erythroid 2-related factor 2 (Nrf2). The results revealed that 4d could significantly inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP+)-induced p38 mitogen-activated protein kinase (MAPK) activation in both in vitro and in vivo PD models, thus inhibiting the NF-κB-mediated neuroinflammation-related apoptosis pathway. Simultaneously, it could promote Nrf2 nuclear transfer, and upregulate the expression of antioxidant phase II detoxification enzymes HO-1 and GCLC, and then reduce oxidative damage.
Evaluation of the Saponin Content in Panax vietnamensis Acclimatized to Lam Dong Province by HPLC–UV/CAD
Authors: Nguyen Huy Truong , Vu-Huynh Kim Long , Nguyen Hien Minh , Le Huong Thuy , Le Thi Hong Van , Park Jeong Hill , Nguyen Minh Duc
Published: September 2021

Panax vietnamensis, or Vietnamese ginseng (VG), an endemic Panax species in Vietnam, possesses a unique saponin profile and interesting biological activities. This plant is presently in danger of extinction due to over-exploitation, resulting in many preservation efforts towards the geographical acclimatization of VG. Yet, no information on the saponin content of the acclimatized VG, an important quality indicator, is available. Here, we analyzed the saponin content in the underground parts of two- to five-year-old VG plants acclimatized to Lam Dong province. Nine characteristic saponins, including notoginsenoside-R1, ginsenoside-Rg1, -Rb1, -Rd, majonoside-R1, -R2 vina-ginsenoside-R2, -R11, and pseudoginsenoside-RT4, were simultaneously determined by HPLC coupled with UV and with a charged aerosol detector (CAD). Analyzing the results illustrated that the detection of characteristic ocotillol-type saponins in VG by CAD presented a superior capacity compared with that of UV, thus implying a preferential choice of CAD for the analysis of VG. The quantitative results indicating the saponin content in the underground parts of VG showed an increasing tendency from two to five years old, with the root and the rhizome exhibiting different saponin accumulation patterns. This is the first study that reveals the preliminary success of VG acclimatization and thereby encourages the continuing efforts to develop this valuable saponin-rich plant.
Photomechanical Polymer Nanocomposites for Drug Delivery Devices
Authors: López-Lugo Jonathan David , Pimentel-Domínguez Reinher , Benítez-Martínez Jorge Alejandro , Hernández-Cordero Juan , Vélez-Cordero Juan Rodrigo , Sánchez-Arévalo Francisco Manuel
Published: September 2021

We demonstrate a novel structure based on smart carbon nanocomposites intended for fabricating laser-triggered drug delivery devices (DDDs). The performance of the devices relies on nanocomposites’ photothermal effects that are based on polydimethylsiloxane (PDMS) with carbon nanoparticles (CNPs). Upon evaluating the main features of the nanocomposites through physicochemical and photomechanical characterizations, we identified the main photomechanical features to be considered for selecting a nanocomposite for the DDDs. The capabilities of the PDMS/CNPs prototypes for drug delivery were tested using rhodamine-B (Rh-B) as a marker solution, allowing for visualizing and quantifying the release of the marker contained within the device. Our results showed that the DDDs readily expel the Rh-B from the reservoir upon laser irradiation and the amount of released Rh-B depends on the exposure time. Additionally, we identified two main Rh-B release mechanisms, the first one is based on the device elastic deformation and the second one is based on bubble generation and its expansion into the device. Both mechanisms were further elucidated through numerical simulations and compared with the experimental results. These promising results demonstrate that an inexpensive nanocomposite such as PDMS/CNPs can serve as a foundation for novel DDDs with spatial and temporal release control through laser irradiation.
Synergistic Action of Membrane-Bound and Water-Soluble Antioxidants in Neuroprotection
Authors: Polutchko Stephanie K. , Glime Gabrielle N. E. , Demmig-Adams Barbara
Published: September 2021

Prevention of neurodegeneration during aging, and support of optimal brain function throughout the lifespan, requires protection of membrane structure and function. We review the synergistic action of different classes of dietary micronutrients, as well as further synergistic contributions from exercise and stress reduction, in supporting membrane structure and function. We address membrane-associated inflammation involving reactive oxygen species (ROS) that produce immune regulators from polyunsaturated fatty acids (PUFAs) of membrane phospholipids. The potential of dietary micronutrients to maintain membrane fluidity and prevent chronic inflammation is examined with a focus on synergistically acting membrane-soluble components (zeaxanthin, lutein, vitamin E, and omega-3 PUFAs) and water-soluble components (vitamin C and various phenolics). These different classes of micronutrients apparently operate in a series of intertwined oxidation-reduction cycles to protect membrane function and prevent chronic inflammation. At this time, it appears that combinations of a balanced diet with regular moderate exercise and stress-reduction practices are particularly beneficial. Effective whole-food-based diets include the Mediterranean and the MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay diet, where DASH stands for Dietary Approaches to Stop Hypertension).
Fabrication of Vertical-Standing Co-MOF Nanoarrays with 2D Parallelogram-like Morphology for Aqueous Asymmetric Electrochemical Capacitors
Authors: Li Leyuan , Mi Hongtian , Jin Yuhong , Ren Dayong , Zhou Kailing , Zhang Qianqian , Liu Jingbing , Wang Hao
Published: September 2021

Metal organic frameworks (MOFs) have been considered as one of the most promising electrode materials for electrochemical capacitors due to their large specific surface area and abundant pore structure. Herein, we report a Co-MOF electrode with a vertical-standing 2D parallelogram-like nanoarray structure on a Ni foam substrate via a one-step solvothermal method. The as-prepared Co-MOF on a Ni foam electrode delivered a high area-specific capacitance of 582.0 mC cm−2 at a current density of 2 mA cm−2 and a good performance rate of 350.0 mC cm−2 at 50 mA cm−2. Moreover, an asymmetric electrochemical capacitor (AEC) device (Co-MOF on Ni foam//AC) was assembled by using the as-prepared Co-MOF on a Ni foam as the cathode and a active carbon-coated Ni foam as the anode to achieve a maximum energy density of 0.082 mW cm−2 at a power density of 0.8 mW cm−2, which still maintained 0.065 mW cm−2 at a high power density of 11.94 mW cm−2. Meanwhile, our assembled device exhibited an excellent cycling stability with a capacitance retention of nearly 100% after 1000 cycles. Therefore, this work provides a simple method to prepare MOF-based material for the application of energy storage and conversion.
Synthesis, Crystal Structure, and Luminescence of Cadmium(II) and Silver(I) Coordination Polymers Based on 1,3-Bis(1,2,4-triazol-1-yl)adamantane
Authors: Marchenko Roman D. , Sukhikh Taisiya S. , Ryadun Alexey A. , Potapov Andrei S.
Published: September 2021

Coordination polymers with a new rigid ligand 1,3-bis(1,2,4-triazol-1-yl)adamantane (L) were prepared by its reaction with cadmium(II) or silver(I) nitrates. Crystal structure of the coordination polymers was determined using single-crystal X-ray diffraction analysis. Silver formed two-dimensional coordination polymer [Ag(L)NO3]n, in which metal ions are linked by 1,3-bis(1,2,4-triazol-1-yl)adamantane ligands, coordinated by nitrogen atoms at positions 2 and 4 of 1,2,4-triazole rings. Layers of the coordination polymer consist of rare 18- and 30-membered {Ag2L2} and {Ag4L4} metallocycles. Cadmium(II) nitrate formed two kinds of one-dimensional coordination polymers depending on the metal-to-ligand ratio used in the synthesis. Coordination polymer [Cd(L)2(NO3)2]n was obtained in case of a 1:2 M:L ratio, while for M:L = 2:1 product {[Cd(L)(NO3)2(CH3OH)]·0.5CH3OH}n was isolated. All coordination polymers demonstrated ligand-centered emission near 450 nm upon excitation at 370 nm.
Incorporation of Biomass-Based Carbon Nanoparticles into Polysulfone Ultrafiltration Membranes for Enhanced Separation and Anti-Fouling Performance
Authors: Zheng Zhiyu , Chen Jingwen , Wu Jiamin , Feng Min , Xu Lei , Yan Nina , Xie Hongde
Published: September 2021

Functionalized carbon nanomaterials are considered to be an efficient modifier for ultrafiltration membranes with enhanced performance. However, most of the reported carbon nanomaterials are derived from unsustainable fossil fuels, while an extra modification is often essential before incorporating the nanomaterials in membranes, thus inevitably increasing the cost and complexity. In this work, novel functionalized biomass-based carbon nanoparticles were prepared successfully from agricultural wastes of corn stalks through simple one-step acid oxidation method. The obtained particles with the size of ~45 nm have excellent dispersibility in both aqueous and dimethyl formamide solutions with abundant oxygen-containing groups and negative potentials, which can endow the polysulfone ultrafiltration membranes with enhanced surface hydrophilicity, larger pore size, more finger-like pores, and lower surface roughness. Therefore, the separation and anti-fouling performance of membranes are improved simultaneously. Meanwhile, the addition of 0.4 wt% nanoparticles was proved to be the best condition for membrane preparation as excess modifiers may lead to particle aggregation and performance recession. It is expected that these biomass-based carbon nanoparticles are potential modifying materials for improving the separation performance and anti-fouling property of the membranes with great simplicity and renewability, which pave a new avenue for membrane modification and agricultural waste utilization.
Social Capital and Self-Perceived Quality of Life-Interrelated Predictors of Mediterranean Diet Adherence in Older Adults
Authors: Apostolaki Ioanna , Pepa Aleks , Vlassopoulos Antonis , Kapsokefalou Maria
Published: September 2021

Living a healthy life in a supporting environment are key elements towards higher diet quality in older age. The Mediterranean Diet in Older Adults (MINOA) study collected cross-sectional data from adults ≥65 years old (n = 436) from April 2014 to November 2015 in rural Crete, aiming to understand the interrelations between Mediterranean Diet adherence, Social Capital and Health-Related Quality of Life (HRQL). Multivariate linear regression, carried out using SPSS 20.0, revealed that both Social Capital and HRQL has a positive impact on Mediterranean Diet adherence after adjustment for confounders and independently of each other. Total Social Capital as well as its Value of Life/Social Agency component (β = 0.04 and β = 0.1, p < 0.05, respectively) had a positive relationship with Mediterranean Diet adherence. As far as HRQL is concerned, only the Physical Health components were found to have a positive association with Mediterranean Diet adherence (β = 0.09, p < 0.001). At the same time Total Social Capital was also seen to have a positive relationship with perceived Physical and Mental Health (β = 0.21 and β = 0.28, p < 0.001, respectively). In a population of older adults Social Capital, HRQL and Mediterranean Diet adherence seem to share intricate interrelations that impact both diet quality and quality of life overall.
The Orexigenic Force of Olfactory Palatable Food Cues in Rats
Authors: Peris-Sampedro Fiona , Stoltenborg Iris , Le May Marie V. , Sole-Navais Pol , Adan Roger A. H. , Dickson Suzanne L.
Published: September 2021

Environmental cues recalling palatable foods motivate eating beyond metabolic need, yet the timing of this response and whether it can develop towards a less palatable but readily available food remain elusive. Increasing evidence indicates that external stimuli in the olfactory modality communicate with the major hub in the feeding neurocircuitry, namely the hypothalamic arcuate nucleus (Arc), but the neural substrates involved have been only partially uncovered. By means of a home-cage hidden palatable food paradigm, aiming to mimic ubiquitous exposure to olfactory food cues in Western societies, we investigated whether the latter could drive the overeating of plain chow in non-food-deprived male rats and explored the neural mechanisms involved, including the possible engagement of the orexigenic ghrelin system. The olfactory detection of a familiar, palatable food impacted upon meal patterns, by increasing meal frequency, to cause the persistent overconsumption of chow. In line with the orexigenic response observed, sensing the palatable food in the environment stimulated food-seeking and risk-taking behavior, which are intrinsic components of food acquisition, and caused active ghrelin release. Our results suggest that olfactory food cues recruited intermingled populations of cells embedded within the feeding circuitry within the Arc, including, notably, those containing the ghrelin receptor. These data demonstrate the leverage of ubiquitous food cues, not only for palatable food searching, but also to powerfully drive food consumption in ways that resonate with heightened hunger, for which the orexigenic ghrelin system is implicated.
Dietary Supplementation with Transgenic Camelina sativa Oil Containing 20:5n-3 and 22:6n-3 or Fish Oil Induces Differential Changes in the Transcriptome of CD3+ T Lymphocytes
Authors: West Annette L. , Miles Elizabeth A. , Han Lihua , Lillycrop Karen A. , Napier Johnathan A. , Calder Philip C. , Burdge Graham C.
Published: September 2021

Eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) are important for leukocyte function. This study investigated whether consuming transgenic Camelina sativa (tCSO) seed oil containing both 20:5n-3 and 22:6n-3 is as effective as fish oil (FO) for increasing the 20:5n-3 and 22:6n-3 content of leukocytes and altering mitogen-induced changes to the T cell transcriptome. Healthy adults (n = 31) consumed 450 mg/day of 20:5n-3 plus 22:6n-3 from either FO or tCSO for 8 weeks. Blood was collected before and after the intervention. 20:5n-3 and 22:6n-3 incorporation from tCSO into immune cell total lipids was comparable to FO. The relative expression of the transcriptomes of mitogen-stimulated versus unstimulated T lymphocytes in a subgroup of 16 women/test oil showed 4390 transcripts were differentially expressed at Baseline (59% up-regulated), 4769 (57% up-regulated) after FO and 3443 (38% up-regulated) after tCSO supplementation. The 20 most altered transcripts after supplementation differed between test oils. The most altered pathways were associated with cell proliferation and immune function. In conclusion, 20:5n-3 and 22:6n-3 incorporation into immune cells from tCSO was comparable to FO and can modify mitogen-induced changes in the T cell transcriptome, contingent on the lipid matrix of the oil.
Chaetomium and Chaetomium-like Species from European Indoor Environments Include Dichotomopilus finlandicus sp. nov.
Authors: Kedves Orsolya , Kocsubé Sándor , Bata Teodóra , Andersson Maria A. , Salo Johanna M. , Mikkola Raimo , Salonen Heidi , Szűcs Attila , Kedves Alfonz , Kónya Zoltán , Vágvölgyi Csaba , Magyar Donát , Kredics László
Published: September 2021

The genus Chaetomium is a frequently occurring fungal taxon world-wide. Chaetomium and Chaetomium-like species occur in indoor environments, where they can degrade cellulose-based building materials, thereby causing structural damage. Furthermore, several species of this genus may also cause adverse effects on human health. The aims of this research were to identify Chaetomium and Chaetomium-like strains isolated from indoor environments in Hungary and Finland, two geographically distant regions of Europe with drier and wetter continental climates, respectively, and to study their morphological and physiological properties, as well as their extracellular enzyme activities, thereby comparing the Chaetomium and Chaetomium-like species isolated from these two different regions of Europe and their properties. Chaetomium and Chaetomium-like strains were isolated from flats and offices in Hungary, as well as from schools, flats, and offices in Finland. Fragments of the translation elongation factor 1α (tef1α), the second largest subunit of RNA polymerase II (rpb2) and β-tubulin (tub2) genes, as well as the internal transcribed spacer (ITS) region of the ribosomal RNA gene cluster were sequenced, and phylogenetic analysis of the sequences performed. Morphological examinations were performed by stereomicroscopy and scanning electron microscopy. Thirty-one Chaetomium sp. strains (15 from Hungary and 16 from Finland) were examined during the study. The most abundant species was Ch. globosum in both countries. In Hungary, 13 strains were identified as Ch. globosum, 1 as Ch. cochliodes, and 1 as Ch. interruptum. In Finland, 10 strains were Ch. globosum, 2 strains were Ch. cochliodes, 2 were Ch. rectangulare, and 2 isolates (SZMC 26527, SZMC 26529) proved to be representatives of a yet undescribed phylogenetic species from the closely related genus Dichotomopilus, which we formally describe here as the new species Dichotomopilus finlandicus. Growth of the isolates was examined at different temperatures (4, 15, 20, 25, 30, 37, 35, 40, and 45 °C), while their extracellular enzyme production was determined spectrophotometrically.
In Silico Prediction of Novel Inhibitors of SARS-CoV-2 Main Protease through Structure-Based Virtual Screening and Molecular Dynamic Simulation
Authors: Halim Sobia Ahsan , Waqas Muhammad , Khan Ajmal , Al-Harrasi Ahmed
Published: September 2021

The unprecedented pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening global health. SARS-CoV-2 has caused severe disease with significant mortality since December 2019. The enzyme chymotrypsin-like protease (3CLpro) or main protease (Mpro) of the virus is considered to be a promising drug target due to its crucial role in viral replication and its genomic dissimilarity to human proteases. In this study, we implemented a structure-based virtual screening (VS) protocol in search of compounds that could inhibit the viral Mpro. A library of >eight hundred compounds was screened by molecular docking into multiple structures of Mpro, and the result was analyzed by consensus strategy. Those compounds that were ranked mutually in the ‘Top-100’ position in at least 50% of the structures were selected and their analogous binding modes predicted simultaneously in all the structures were considered as bioactive poses. Subsequently, based on the predicted physiological and pharmacokinetic behavior and interaction analysis, eleven compounds were identified as ‘Hits’ against SARS-CoV-2 Mpro. Those eleven compounds, along with the apo form of Mpro and one reference inhibitor (X77), were subjected to molecular dynamic simulation to explore the ligand-induced structural and dynamic behavior of Mpro. The MM-GBSA calculations reflect that eight out of eleven compounds specifically possess high to good binding affinities for Mpro. This study provides valuable insights to design more potent and selective inhibitors of SARS-CoV-2 Mpro.
The EyeFlowCell: Development of a 3D-Printed Dissolution Test Setup for Intravitreal Dosage Forms
Authors: Auel Tobias , Großmann Linus , Schulig Lukas , Weitschies Werner , Seidlitz Anne
Published: September 2021

An in vitro dissolution model, the so-called EyeFlowCell (EFC), was developed to test intravitreal dosage forms, simulating parameters such as the gel-like consistency of the vitreous body. The developed model consists of a stereolithography 3D-printed flow-through cell with a polyacrylamide (PAA) gel as its core. This gel needed to be coated with an agarose sheath because of its low viscosity. Drug release from hydroxypropyl methylcellulose-based implants containing either triamcinolone acetonide or fluorescein sodium was studied in the EFC using a schematic eye movement by the EyeMovementSystem (EyeMoS). For comparison, studies were performed in USP apparatus 4 and USP apparatus 7. Significantly slower drug release was observed in the PAA gel for both model drugs compared with the compendial methods. Drug release from fluorescein sodium-containing model implants was completed after 40 min in USP apparatus 4, whereas drug release in the gel-based EFC lasted 72 h. Drug release from triamcinolone acetonide-containing model implants was completed after 35 min in USP apparatus 4 and after 150 min in USP apparatus 7, whereas this was delayed until 96 h in the EFC. These results suggest that compendial release methods may overestimate the drug release rate in the human vitreous body. Using a gel-based in vitro release system such as the EFC may better predict drug release.
Pharmacokinetics of Levodopa and 3-O-Methyldopa in Parkinsonian Patients Treated with Levodopa and Ropinirole and in Patients with Motor Complications
Authors: Adamiak-Giera Urszula , Jawień Wojciech , Pierzchlińska Anna , Białecka Monika , Kobierski Jan Dariusz , Janus Tomasz , Gawrońska-Szklarz Barbara
Published: September 2021

Parkinson’s disease (PD) is a progressive, neurodegenerative disorder primarily affecting dopaminergic neuronal systems, with impaired motor function as a consequence. The most effective treatment for PD remains the administration of oral levodopa (LD). Long-term LD treatment is frequently associated with motor fluctuations and dyskinesias, which exert a serious impact on a patient’s quality of life. The aim of our study was to determine the pharmacokinetics of LD: used as monotherapy or in combination with ropinirole, in patients with advanced PD. Furthermore, an effect of ropinirole on the pharmacokinetics of 3-OMD (a major LD metabolite) was assessed. We also investigated the correlation between the pharmacokinetic parameters of LD and 3-OMD and the occurrence of motor complications. Twenty-seven patients with idiopathic PD participated in the study. Thirteen patients received both LD and ropinirole, and fourteen administered LD monotherapy. Among 27 patients, twelve experienced fluctuations and/or dyskinesias, whereas fifteen were free of motor complications. Inter- and intra-individual variation in the LD and 3-OMD concentrations were observed. There were no significant differences in the LD and 3-OMD concentrations between the patients treated with a combined therapy of LD and ropinirole, and LD monotherapy. There were no significant differences in the LD concentrations in patients with and without motor complications; however, plasma 3-OMD levels were significantly higher in patients with motor complications. A linear one-compartment pharmacokinetic model with the first-order absorption was adopted for LD and 3-OMD. Only mean exit (residence) time for 3-OMD was significantly shorter in patients treated with ropinirole. Lag time, V/F, CL/F and tmax of LD had significantly lower values in patients with motor complications. On the other hand, AUC were significantly higher in these patients, both for LD and 3-OMD. 3-OMD Cmax was significantly higher in patients with motor complications as well. Our results showed that ropinirole does not influence LD or 3-OMD concentrations. Higher 3-OMD levels play a role in inducing motor complications during long-term levodopa therapy.
Ultrasound-Responsive Smart Drug Delivery System of Lipid Coated Mesoporous Silica Nanoparticles
Authors: Amin Muhammad Umair , Ali Sajid , Tariq Imran , Ali Muhammad Yasir , Pinnapreddy Shashank Reddy , Preis Eduard , Wölk Christian , Harvey Richard D. , Hause Gerd , Brüßler Jana , Bakowsky Udo
Published: September 2021

The immediate release of chemotherapeutics at the target site, along with no premature release in circulation is always challenging. The purpose of this study was to develop a stimuli responsive drug delivery system, composed of lipid supported mesoporous silica nanoparticles (MSNPs) for triggered drug release at the target site and simultaneously avoiding the premature release. MSNPs with a higher drug loading capacity and very slow release were designed so as to enhance release by FDA approved US-irradiation. Doxorubicin, as a model drug, and perfluoropentane (PFP) as a US responsive material, were entrapped in the porous structure of MSNPs. Lipid coating enhanced the cellular uptake and in addition provided a gatekeeping effect at the pore opening to reduce premature release. The mechanical and thermal effects of US induced the conversion of liquid PFP to a gaseous form that was able to rupture the lipid layer, resulting in triggered drug release. The prolonged stability profile and non-toxic behavior made them suitable candidate for the delivery of anticancer drugs. This smart system, with the abilities of better cellular uptake and higher cytotoxic effects on US-irradiation, would be a good addition to the applied side of chemotherapeutic advanced drug delivery systems.
New RNA-Based Breakthroughs in Alzheimer’s Disease Diagnosis and Therapeutics
Authors: Riscado Micaela , Baptista Bruno , Sousa Fani
Published: September 2021

Dementia is described as the fifth leading cause of death worldwide and Alzheimer’s disease (AD) is recognized as the most common, causing a huge impact on health costs and quality of patients’ lives. The main hallmarks that are commonly associated with the pathologic process are amyloid deposition, pathologic Tau phosphorylation and neurodegeneration. It is still unclear how these events are linked to the disease progression, due to the complex pathologic mechanisms. Nevertheless, several hypotheses have been proposed for a better understanding of AD. The AD diagnosis is performed by using a combination of several tools to detect β-amyloid peptide (Aβ) deposits and modifications in cognitive performance, sometimes being expensive and invasive. In the treatment field, there is still an absence of effective treatments to delay or stop the progression of the disease, with most of the approved drugs used to relieve symptoms, and all of them with significant adverse side effects. Considering all limitations, the need to establish new and more effective diagnostic and therapeutic strategies becomes clear. This review aims not only to describe the disease and its impact but also to collect the currently available diagnostic and therapeutic strategies, highlighting new promising RNA-based strategies for AD.
Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Brain Levels of Drug in Rat
Authors: Sánchez-Dengra Bárbara , Gonzalez-Alvarez Isabel , Bermejo Marival , Gonzalez-Alvarez Marta
Published: September 2021

One of the main obstacles in neurological disease treatment is the presence of the blood–brain barrier. New predictive high-throughput screening tools are essential to avoid costly failures in the advanced phases of development and to contribute to the 3 Rs policy. The objective of this work was to jointly develop a new in vitro system coupled with a physiological-based pharmacokinetic (PBPK) model able to predict brain concentration levels of different drugs in rats. Data from in vitro tests with three different cells lines (MDCK, MDCK-MDR1 and hCMEC/D3) were used together with PK parameters and three scaling factors for adjusting the model predictions to the brain and plasma profiles of six model drugs. Later, preliminary quantitative structure–property relationships (QSPRs) were constructed between the scaling factors and the lipophilicity of drugs. The predictability of the model was evaluated by internal validation. It was concluded that the PBPK model, incorporating the barrier resistance to transport, the disposition within the brain and the drug–brain binding combined with MDCK data, provided the best predictions for passive diffusion and carrier-mediated transported drugs, while in the other cell lines, active transport influence can bias predictions.
Nanocrystalline Suspensions of Irbesartan Enhance Oral Bioavailability by Improving Drug Solubility and Leading Endocytosis Uptake into the Intestine
Authors: Deguchi Saori , Ogata Fumihiko , Watanabe Masaki , Otake Hiroko , Yamamoto Naoki , Kawasaki Naohito , Nagai Noriaki
Published: September 2021

We attempted to design irbesartan nanocrystalline (IRB-NC) suspensions by the bead mill method, and we evaluated the bioavailability (BA) in the oral administration of the nanocrystalline drug. The mean particle size of the IRB-NC suspensions was approximately 140 nm, and the crystalline structure of irbesartan in these suspensions was different using the bead mill method. The aggregation and degradation of irbesartan were not observed for one month, and the solubility increased. Moreover, the inclusion complex formation of IRB-NC suspensions with 2-hydroxypropyl-β-cyclodextrin was higher than that in traditional IRB powder (IRB-P). In addition, the intestinal absorption of IRB-NC suspensions was higher than that of IRB-P suspensions, and the reducing effect on blood pressure in spontaneously hypertensive SHR-SP rats orally administered IRB-NC suspensions was significantly higher than in those administered IRB-P suspensions. On the other hand, the intestinal penetration of IRB-NC suspensions was attenuated by the inhibitors of clathrin-dependent endocytosis (CME). In conclusion, we improved the low oral BA of irbesartan by preparing IRB-NC suspensions and showed that both the solubility and CME are related to the enhanced intestinal absorption of IRB-NC suspensions, resulting in an increase in their antihypertensive effect. These findings provide significant information for the development of oral nanomedicines.
A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions
Authors: Saad Mabroka H. , Badierah Raied , Redwan Elrashdy M. , El-Fakharany Esmail M.
Published: September 2021

Extracellular vesicles (EVs) subtype, exosome is an extracellular nano-vesicle that sheds from cells’ surface and originates as intraluminal vesicles during endocytosis. Firstly, it was thought to be a way for the cell to get rid of unwanted materials as it loaded selectively with a variety of cellular molecules, including RNAs, proteins, and lipids. However, it has been found to play a crucial role in several biological processes such as immune modulation, cellular communication, and their role as vehicles to transport biologically active molecules. The latest discoveries have revealed that many viruses export their viral elements within cellular factors using exosomes. Hijacking the exosomal pathway by viruses influences downstream processes such as viral propagation and cellular immunity and modulates the cellular microenvironment. In this manuscript, we reviewed exosomes biogenesis and their role in the immune response to viral infection. In addition, we provided a summary of how some pathogenic viruses hijacked this normal physiological process. Viral components are harbored in exosomes and the role of these exosomes in viral infection is discussed. Understanding the nature of exosomes and their role in viral infections is fundamental for future development for them to be used as a vaccine or as a non-classical therapeutic strategy to control several viral infections.
Pre-Clinical Pharmacokinetic Characterization, Tissue Distribution, and Excretion Studies of Novel Edaravone Oral Prodrug, TEJ-1704
Authors: Kang Dong Wook , Kim Ju Hee , Kim Kyung Min , Cho Seok-jin , Jang Hee-Woon , Chang Ji Won , Dong Seung Myung , Lim Jee Woong , Kim Jae-Sun , Cho Hea-Young
Published: September 2021

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger approved for the treatment of amyotrophic lateral sclerosis, a fatal neuromuscular disease. Edaravone is administered as an intravenous infusion over 60 min for several treatment cycles. To ease the burden of patients and caregivers, the oral formulation of edaravone has been developed. The purpose of this study was to evaluate pharmacokinetics and tissue distribution of TEJ-1704, an edaravone oral prodrug, in male Sprague Dawley rats and beagle dogs. Animal experiments were conducted using Sprague Dawley rats and beagle dogs to evaluate pharmacokinetics, tissue distribution, and excretion of TEJ-1704. Blood, tissues, cerebrospinal fluid, urine, and feces samples were collected at designated sampling time after intravenous (IV) or oral (PO) administration of edaravone or TEJ-1704. A modified bioanalysis method was developed to quantify edaravone in samples including plasma, tissues, cerebrospinal fluid, urine, and feces. The bioanalysis method was validated and successfully applied to pharmacokinetics, tissue distribution, and excretion studies of the novel edaravone prodrug. Although plasma Cmax of TEJ-1704 was low, groups administered with TEJ-1704 had high AUCinf, suggesting continuous metabolism of TEJ-1704 into edaravone. Groups treated with TEJ-1704 also showed lower CSF distribution than the control groups. After the administration of TEJ-1704, the majority of edaravone was distributed to the heart, lung, and kidney. It was excreted equally via urine and feces. The pharmacokinetics, tissue distribution, and excretion of TEJ-1704, a novel edaravone oral prodrug, were successfully characterized. Additional studies are needed to fully understand the difference between TEJ-1704 and edaravone and determine the potency of TEJ-1704.
Gold–Protein Composite Nanoparticles for Enhanced X-ray Interactions: A Potential Formulation for Triggered Release
Authors: van Ballegooie Courtney , Man Alice , Pallaoro Alessia , Bally Marcel , Gates Byron D. , Yapp Donald T.
Published: September 2021

Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy; fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs.
Nanosystems in Cosmetic Products: A Brief Overview of Functional, Market, Regulatory and Safety Concerns
Authors: Ferraris Chiara , Rimicci Clara , Garelli Sara , Ugazio Elena , Battaglia Luigi
Published: September 2021

Nanosystems exhibit various innovative physico-chemical properties as well as a range of cosmetic functions, including increased skin retention for loaded compounds. The worldwide nano-market has therefore been consistently extensive in recent decades. This review summarizes the most important properties of nanosystems that are employed in cosmetics, including composition, functions and interactions with skin, with particular attention being paid to marketed products. Moreover, the worldwide regulatory landscape of nanomaterials used as cosmetic ingredients is considered, and the main safety concerns are indicated. In general, advanced physico-chemical characterization is preliminarily needed to assess the safety of nanomaterials for human health and the environment. However, there is currently a shortfall in global legislation as a universally accepted and unambiguous definition of a nanomaterial is still lacking. Therefore, each country follows its own regulations. Anyhow, the main safety concerns arise from the European context, which is the most restrictive. Accordingly, the poor dermal permeation of nanomaterials generally limits their potential toxic effects, which should be mainly ascribed to unwanted or accidental exposure routes.
Mechanical Properties of Flexible TPU-Based 3D Printed Lattice Structures: Role of Lattice Cut Direction and Architecture
Authors: Beloshenko Victor , Beygelzimer Yan , Chishko Vyacheslav , Savchenko Bogdan , Sova Nadiya , Verbylo Dmytro , Voznyak Andrei , Vozniak Iurii
Published: September 2021

This study addresses the mechanical behavior of lattice materials based on flexible thermoplastic polyurethane (TPU) with honeycomb and gyroid architecture fabricated by 3D printing. Tensile, compression, and three-point bending tests were chosen as mechanical testing methods. The honeycomb architecture was found to provide higher values of rigidity (by 30%), strength (by 25%), plasticity (by 18%), and energy absorption (by 42%) of the flexible TPU lattice compared to the gyroid architecture. The strain recovery is better in the case of gyroid architecture (residual strain of 46% vs. 31%). TPUs with honeycomb architecture are characterized by anisotropy of mechanical properties in tensile and three-point bending tests. The obtained results are explained by the peculiarities of the lattice structure at meso- and macroscopic level and by the role of the pore space.
Model Composites Based on Poly(lactic acid) and Bioactive Glass Fillers for Bone Regeneration
Authors: Lacambra-Andreu Xavier , Dergham Nora , Magallanes-Perdomo Marlin , Meille Sylvain , Chevalier Jérôme , Chenal Jean-Marc , Maazouz Abderrahim , Lamnawar Khalid
Published: September 2021

Poly(l-lactide-co-d,l-lactide) PDLA/45S5 Bioglass® (BG) composites for medical devices were developed using an original approach based on a thermal treatment of BG prior to processing. The aim of the present work is to gain a fundamental understanding of the relationships between the morphology, processing conditions and final properties of these biomaterials. A rheological study was performed to evaluate and model the PDLA/BG degradation during processing. The filler contents, as well as their thermal treatments, were investigated. The degradation of PDLA was also investigated by Fourier transform infrared (FTIR) spectroscopy, size-exclusion chromatography (SEC) and mechanical characterization. The results highlight the value of thermally treating the BG in order to control the degradation of the polymer during the process. The present work provides a guideline for obtaining composites with a well-controlled particle dispersion, optimized mechanical properties and limited degradation of the PDLA matrix.
Enhanced Chemical and Electrochemical Stability of Polyaniline-Based Layer-by-Layer Films
Authors: Firda Putri Bintang Dea , Malik Yoga Trianzar , Oh Jun Kyun , Wujcik Evan K. , Jeon Ju-Won
Published: September 2021

Polyaniline (PANI) has been widely used as an electroactive material in various applications including sensors, electrochromic devices, solar cells, electroluminescence, and electrochemical energy storage, owing to PANI’s unique redox properties. However, the chemical and electrochemical stability of PANI-based materials is not sufficiently high to maintain the performance of devices under many practical applications. Herein, we report a route to enhancing the chemical and electrochemical stability of PANI through layer-by-layer (LbL) assembly. PANI was assembled with different types of polyelectrolytes, and a comparative study between three different PANI-based layer-by-layer (LbL) films is presented here. Polyacids of different acidity and molecular structure, i.e., poly(acrylic acid) (PAA), polystyrene sulfonate (PSS), and tannic acid (TA), were used. The effect of polyacids’ acidity on film growth, conductivity, and chemical and electrochemical stability of PANI was investigated. The results showed that the film growth of the LbL system depended on the acidic strength of the polyacids. All LbL films exhibited improved chemical and electrochemical stability compared to PANI films. The doping level of PANI was strongly affected by the type of dopants, resulting in different chemical and electrochemical properties; the strongest polyacid (PSS) can provide the highest conductivity and chemical stability of conductive PANI. However, the electrochemical stability of PANI/PAA was found to be better than all the other films.
Nematic Structures under Conical Anchoring at Various Director Tilt Angles Specified by Polymethacrylate Compositions
Authors: Kostikov Denis A. , Krakhalev Mikhail N. , Prishchepa Oxana O. , Zyryanov Victor Ya.
Published: September 2021

Dependence of the director tilt angle of nematic liquid crystal (LC) under conical anchoring from the two-component polymer mixture composition has been studied. We varied the ratio of poly(isobutyl methacrylate) (PiBMA), which specifies a conical anchoring for the nematic liquid crystal LN-396, and poly(methylmethacrylate) (PMMA) assigning a tangential alignment for the same nematic. An oblique incidence light technique to determine a tilt angle has been used. It has been shown that the tilt angle increases from 0∘ to 47.7∘ when PiBMA:PMMA ratio changes in the range 30:70 to 100:0. The specific optical textures viewed under the polarizing microscope and proper orientational structures have been considered for various compositions of the polymer films. An electric field action on the formed orientational structures has been investigated. The obtained results are promising for the application in various electro-optical LC devices with a conical anchoring in which the director tilt angle is a crucial parameter: a controlled diffraction gratings, an electrically operated achromatic rotators of linear light polarization, etc.
The Interfacial Structure and Adhesion Mechanism of N-(2-Aminoethyl)-3-aminopropyltrimethoxysilane and Epoxy Modified Silicone Tie-Coating to Epoxy Primer
Authors: Zhang Hongyang , Zhang Zhanping , Qi Yuhong , Yang Qiang
Published: September 2021

The matching application of silicone antifouling coating and epoxy primer is a major problem in engineering. Novel epoxy-modified silicone tie-coating was prepared to tie epoxy primer and silicone antifouling coating. Firstly, N-(2-Aminoethyl)-3-aminopropyltrimethoxysilane was mechanically mixed with bisphenol A epoxy resin to form silylated epoxy resin, then the silylated epoxy resin was uniformly mixed with hydroxy-terminated polydimethylsiloxane and a curing agent and catalyst for coating. An infrared spectrometer, differential scanning calorimeter and tensile tests were used to investigate the chemical structure, phase transition temperature and mechanical properties of the tie-coatings. The interlaminar adhesion of the matching coating system was tested and analyzed by a peel-off test and a shear test. Fracture morphology was observed by scanning using an electron microscope. The results showed that crosslinking density of the tie-coating, the elastic modulus and the tensile strength of the coating increased with an increasing epoxy content, but fracture elongation decreased. The shear strength of the matching coating system is 0.37 MPa, and it shows a good tie performance. The maximum anti-peeling rate of the tie-coating on the epoxy primer reaches 100%.