bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide–Protein Interactions: From Drug Design to Supramolecular Biomaterials
Authors: Caporale Andrea , Adorinni Simone , Lamba Doriano , Saviano Michele
Published: February 2021

The self-recognition and self-assembly of biomolecules are spontaneous processes that occur in Nature and allow the formation of ordered structures, at the nanoscale or even at the macroscale, under thermodynamic and kinetic equilibrium as a consequence of specific and local interactions. In particular, peptides and peptidomimetics play an elected role, as they may allow a rational approach to elucidate biological mechanisms to develop new drugs, biomaterials, catalysts, or semiconductors. The forces that rule self-recognition and self-assembly processes are weak interactions, such as hydrogen bonding, electrostatic attractions, and van der Waals forces, and they underlie the formation of the secondary structure (e.g., α-helix, β-sheet, polyproline II helix), which plays a key role in all biological processes. Here, we present recent and significant examples whereby design was successfully applied to attain the desired structural motifs toward function. These studies are important to understand the main interactions ruling the biological processes and the onset of many pathologies. The types of secondary structure adopted by peptides during self-assembly have a fundamental importance not only on the type of nano- or macro-structure formed but also on the properties of biomaterials, such as the types of interaction, encapsulation, non-covalent interaction, or covalent interaction, which are ultimately useful for applications in drug delivery.
Probing the Role of the Conserved Arg174 in Formate Dehydrogenase by Chemical Modification and Site-Directed Mutagenesis
Authors: Alqarni Mohammed Hamed , Foudah Ahmed Ibrahim , Muharram Magdy Mohamed , Budurian Haritium , Labrou Nikolaos E.
Published: February 2021

The reactive adenosine derivative, adenosine 5′-O-[S-(4-hydroxy-2,3-dioxobutyl)]-thiophosphate (AMPS-HDB), contains a dicarbonyl group linked to the purine nucleotide at a position equivalent to the pyrophosphate region of NAD+. AMPS-HDB was used as a chemical label towards Candida boidinii formate dehydrogenase (CbFDH). AMPS-HDB reacts covalently with CbFDH, leading to complete inactivation of the enzyme activity. The inactivation kinetics of CbFDH fit the Kitz and Wilson model for time-dependent, irreversible inhibition (KD = 0.66 ± 0.15 mM, first order maximum rate constant k3 = 0.198 ± 0.06 min−1). NAD+ and NADH protects CbFDH from inactivation by AMPS-HDB, showing the specificity of the reaction. Molecular modelling studies revealed Arg174 as a candidate residue able to be modified by the dicarbonyl group of AMPS-HDB. Arg174 is a strictly conserved residue among FDHs and is located at the Rossmann fold, the common mononucleotide-binding motif of dehydrogenases. Arg174 was replaced by Asn, using site-directed mutagenesis. The mutant enzyme CbFDHArg174Asn was showed to be resistant to inactivation by AMPS-HDB, confirming that the guanidinium group of Arg174 is the target for AMPS-HDB. The CbFDHArg174Asn mutant enzyme exhibited substantial reduced affinity for NAD+ and lower thermostability. The results of the study underline the pivotal and multifunctional role of Arg174 in catalysis, coenzyme binding and structural stability of CbFDH.
Effect of Different Surface Treatment Methods on Bond Strength of Dental Ceramics to Dental Hard Tissues: A Systematic Review
Authors: Malysa Andrzej , Wezgowiec Joanna , Orzeszek Sylwia , Florjanski Wojciech , Zietek Marek , Wieckiewicz Mieszko
Published: February 2021

For long-term successful use of ceramic materials in dental procedures, it is necessary to ensure reliable bonding of restorations to dental substrates. This can be achieved by the application of a proper luting cement and through additional surface conditioning. The present systematic review summarizes the most up-to-date evidence on the use of different surface modification methods to enhance the bond strength of dental ceramics to the hard tissues of the teeth. The authors of the review searched the Web of Science, Scopus, and MEDLINE databases to identify relevant articles published between 1 January 2010 and 1 January 2020. A total of 4892 records were identified, and after screening, the full text of 159 articles was evaluated, which finally resulted in the inclusion of 19 studies. The available reports were found to be heterogeneous in terms of materials and methodology, and therefore, only within-studies comparison was performed instead of comparison between studies. A statistically significant difference in the bond strength between the samples treated with different methods of surface conditioning, or between conditioned and nonconditioned samples, was revealed by most of the studies. Predominantly, the studies showed that a combination of mechanical and chemical methods was the most effective way of enhancing bond strength. Artificial aging and luting cement were also identified as the factors significantly influencing bond strength.
Towards Conformation-Sensitive Inhibition of Gyrase: Implications of Mechanistic Insight for the Identification and Improvement of Inhibitors
Authors: Klostermeier Dagmar
Published: February 2021

Gyrase is a bacterial type IIA topoisomerase that catalyzes negative supercoiling of DNA. The enzyme is essential in bacteria and is a validated drug target in the treatment of bacterial infections. Inhibition of gyrase activity is achieved by competitive inhibitors that interfere with ATP- or DNA-binding, or by gyrase poisons that stabilize cleavage complexes of gyrase covalently bound to the DNA, leading to double-strand breaks and cell death. Many of the current inhibitors suffer from severe side effects, while others rapidly lose their antibiotic activity due to resistance mutations, generating an unmet medical need for novel, improved gyrase inhibitors. DNA supercoiling by gyrase is associated with a series of nucleotide- and DNA-induced conformational changes, yet the full potential of interfering with these conformational changes as a strategy to identify novel, improved gyrase inhibitors has not been explored so far. This review highlights recent insights into the mechanism of DNA supercoiling by gyrase and illustrates the implications for the identification and development of conformation-sensitive and allosteric inhibitors.
Crocus sativus L. Extracts and Its Constituents Crocins and Safranal; Potential Candidates for Schizophrenia Treatment?
Authors: Pitsikas Nikolaos
Published: February 2021

Schizophrenia is a chronic mental devastating disease. Current therapy suffers from various limitations including low efficacy and serious side effects. Thus, there is an urgent necessity to develop new antipsychotics with higher efficacy and safety. The dried stigma of the plant Crocus sativus L., (CS) commonly known as saffron, are used in traditional medicine for various purposes. It has been demonstrated that saffron and its bioactive components crocins and safranal exert a beneficial action in different pathologies of the central nervous system such as anxiety, depression, epilepsy and memory problems. Recently, their role as potential antipsychotic agents is under investigation. In the present review, I intended to critically assess advances in research of these molecules for the treatment of schizophrenia, comment on their advantages over currently used neuroleptics as well-remaining challenges. Up to our days, few preclinical studies have been conducted to this end. In spite of it, results are encouraging and strongly corroborate that additional research is mandatory aiming to definitively establish a role for saffron and its bioactive components for the treatment of schizophrenia.
Broadband Visible Light-Absorbing [70]Fullerene-BODIPY-Triphenylamine Triad: Synthesis and Application as Heavy Atom-Free Organic Triplet Photosensitizer for Photooxidation
Authors: Zhu San-E , Zhang Jian-Hui , Gong Yu , Dou Li-Feng , Mao Li-Hua , Lu Hong-Dian , Wei Chun-Xiang , Chen Hong , Wang Xue-Fei , Yang Wei
Published: February 2021

A broadband visible light-absorbing [70]fullerene-BODIPY-triphenylamine triad (C70-B-T) has been synthesized and applied as a heavy atom-free organic triplet photosensitizer for photooxidation. By attaching two triphenylmethyl amine units (TPAs) to the π-core of BODIPY via ethynyl linkers, the absorption range of the antenna is extended to 700 nm with a peak at 600 nm. Thus, the absorption spectrum of C70-B-T almost covers the entire UV–visible region (270–700 nm). The photophysical processes are investigated by means of steady-state and transient spectroscopies. Upon photoexcitation at 339 nm, an efficient energy transfer (ET) from TPA to BODIPY occurs both in C70-B-T and B-T, resulting in the appearance of the BODIPY emission at 664 nm. Direct or indirect (via ET) excitation of the BODIPY-part of C70-B-T is followed by photoinduced ET from the antenna to C70, thus the singlet excited state of C70 (1C70*) is populated. Subsequently, the triplet excited state of C70 (3C70*) is produced via the intrinsic intersystem crossing of C70. The photooxidation ability of C70-B-T was studied using 1,5-dihydroxy naphthalene (DHN) as a chemical sensor. The photooxidation efficiency of C70-B-T is higher than that of the individual components of C70-1 and B-T, and even higher than that of methylene blue (MB). The photooxidation rate constant of C70-B-T is 1.47 and 1.51 times as that of C70-1 and MB, respectively. The results indicate that the C70-antenna systems can be used as another structure motif for a heavy atom-free organic triplet photosensitizer.
Expression of Luteinizing Hormone-Releasing Hormone (LHRH) and Type-I LHRH Receptor in Transitional Cell Carcinoma Type of Human Bladder Cancer
Authors: Szabó Zsuzsanna , Dezső Balázs , Fodor Klára , Szegedi Krisztián , Flaskó Tibor , Szabó Erzsébet , Oláh Gábor , Sipos Éva , Dobos Nikoletta , Gardi János , Schally Andrew V. , Halmos Gábor
Published: February 2021

Bladder cancer (BC) is the tenth most frequently detected cancer in both sexes. Type-I luteinizing hormone-releasing hormone (LHRH) receptor (LHRH-R-I) is expressed not only in the pituitary, but also in several types of cancer disease. There are few data about LHRH-R-I expression in human BC. This study aimed to investigate the expression of LHRH and LHRH-R-I in the transitional cell carcinoma (TCC) type of human BC. RNA was extracted from 24 human bladder tumor specimens and three BC cell lines. RT-PCR was performed to detect mRNA for LHRH and LHRH-R-I. The protein of LHRH-R-I was further studied by immunohistochemistry (IHC), ligand competition assay, and Western Blot. PCR products of LHRH were found in 19 of 24 (79%) specimens and mRNA of LHRH-R-I was detected in 20 of 24 specimens (83%). Positive immunostaining for LHRH-R-I with different expression intensity was found in all samples examined, showing negative correlation with TCC grade. Radioligand binding studies also showed the presence of specific LHRH-R-I and high affinity binding of LHRH analogs. The high incidence of LHRH-R in BC suggests that it could serve as a molecular target for therapy of human BC with cytotoxic LHRH analogs or modern powerful antagonistic analogs of LHRH.
Morus alba Prevented the Cyclophosphamide Induced Somatic and Germinal Cell Damage in Male Rats by Ameliorating the Antioxidant Enzyme Levels
Authors: Ghosh Abhijit , Rabbani Syed Imam , Asdaq Syed Mohammed Basheeruddin , Mohzari Yahya , Alrashed Ahmed , Najib Alajami Hamdan , Othman Aljohani Awad , Ali Al Mushtawi Abdullah , Sultan Alenazy Majed , Fahad Alamer Rakan , Khalid Alanazi Abdulmajead
Published: February 2021

Cytogenetic analysis is essential to determine the effect of mutagens and antimutagens on genetic material. This study was done to evaluate the protective effect of root bark extract of Morus alba (M. alba) against cyclophosphamide induced somatic and germinal cell damage in male rats. The ethanolic extract of M. alba (0.25, 0.5 and 1 g/kg, 2 weeks) was evaluated against cyclophosphamide (75 mg/kg, single dose) induced nuclear damage. The sampling was done after 48 h of the clastogen treatment. The somatic and germinal nuclear damage was studied by bone marrow micronucleus and sperm analysis, respectively. Serum superoxide and catalase levels were estimated to determine the antioxidant status in each group. The results were analyzed statistically to find the significant variation. The administration of M. alba for 2 weeks suppressed dose-dependently the changes induced by cyclophosphamide. M. alba (0.5 g/kg) decreased the frequency of micronucleated erythrocyte, sperm shape abnormality and enhanced the sperm count, sperm motility and polychromatic-normochromatic erythrocytes ratio significantly (p < 0.05) in comparison with the cyclophosphamide treated group. The highest tested dose of M. alba (1 g/kg) produced more prominent suppression (p < 0.01) in the cyclophosphamide-induced somatic and germinal cell defects. The results also showed significant (p < 0.05) improvement in the serum antioxidant enzymes levels with M. alba when compared with the challenge group. The lower dose of M. alba extract (0.25 g/kg) prevented the CP-induced changes but was found to be statistically insignificant. Therefore, antimutagenic potential of the high dose of the extract of M. alba is possibly due to its antioxidant nature. The ability of the M. alba extract to prevent the nuclear damage could play an important role in overcoming several mutational defects that are associated with anticancer chemotherapy.
Rapid MALDI-MS Assays for Drug Quantification in Biological Matrices: Lessons Learned, New Developments, and Future Perspectives
Authors: Fresnais Margaux , Yildirim Esra , Karabulut Seda , Jäger Dirk , Zörnig Inka , Benzel Julia , Pajtler Kristian W. , Pfister Stefan M. , Burhenne Jürgen , Haefeli Walter E. , Longuespée Rémi
Published: February 2021

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has rarely been used in the field of therapeutic drug monitoring, partly because of the complexity of the ionization processes between the compounds to be quantified and the many MALDI matrices available. The development of a viable MALDI-MS method that meets regulatory guidelines for bioanalytical method validation requires prior knowledge of the suitability of (i) the MALDI matrix with the analyte class and properties for ionization, (ii) the crystallization properties of the MALDI matrix with automation features, and (iii) the MS instrumentation used to achieve sensitive and specific measurements in order to determine low pharmacological drug concentrations in biological matrices. In the present hybrid article/white paper, we review the developments required for the establishment of MALDI-MS assays for the quantification of drugs in tissues and plasma, illustrated with concrete results for the different steps. We summarize the necessary parameters that need to be controlled for the successful development of fully validated MALDI-MS methods according to regulatory authorities, as well as currently unsolved problems and promising ways to address them. Finally, we propose an expert opinion on future perspectives and needs in order to establish MALDI-MS as a universal method for therapeutic drug monitoring.
Forced Vibration Analysis of Composite Beams Reinforced by Carbon Nanotubes
Authors: Civalek Ömer , Akbaş Şeref D. , Akgöz Bekir , Dastjerdi Shahriar
Published: February 2021

This paper presents forced vibration analysis of a simply supported beam made of carbon nanotube-reinforced composite material subjected to a harmonic point load at the midpoint of beam. The composite beam is made of a polymeric matrix and reinforced the single-walled carbon nanotubes with their various distributions. In the beam kinematics, the first-order shear deformation beam theory was used. The governing equations of problem were derived by using the Lagrange procedure. In the solution of the problem, the Ritz method was used, and algebraic polynomials were employed with the trivial functions for the Ritz method. In the solution of the forced vibration problem, the Newmark average acceleration method was applied in the time history. In the numerical examples, the effects of carbon nanotube volume fraction, aspect ratio, and dynamic parameters on the forced vibration response of carbon nanotube-reinforced composite beams are investigated. In addition, some comparison studies were performed, with special results of published papers to validate the using formulations.
Elastostatics of Bernoulli–Euler Beams Resting on Displacement-Driven Nonlocal Foundation
Authors: Vaccaro Marzia Sara , Pinnola Francesco Paolo , Marotti de Sciarra Francesco , Barretta Raffaele
Published: February 2021

The simplest elasticity model of the foundation underlying a slender beam under flexure was conceived by Winkler, requiring local proportionality between soil reactions and beam deflection. Such an approach leads to well-posed elastostatic and elastodynamic problems, but as highlighted by Wieghardt, it provides elastic responses that are not technically significant for a wide variety of engineering applications. Thus, Winkler’s model was replaced by Wieghardt himself by assuming that the beam deflection is the convolution integral between soil reaction field and an averaging kernel. Due to conflict between constitutive and kinematic compatibility requirements, the corresponding elastic problem of an inflected beam resting on a Wieghardt foundation is ill-posed. Modifications of the original Wieghardt model were proposed by introducing fictitious boundary concentrated forces of constitutive type, which are physically questionable, being significantly influenced on prescribed kinematic boundary conditions. Inherent difficulties and issues are overcome in the present research using a displacement-driven nonlocal integral strategy obtained by swapping the input and output fields involved in Wieghardt’s original formulation. That is, nonlocal soil reaction fields are the output of integral convolutions of beam deflection fields with an averaging kernel. Equipping the displacement-driven nonlocal integral law with the bi-exponential averaging kernel, an equivalent nonlocal differential problem, supplemented with non-standard constitutive boundary conditions involving nonlocal soil reactions, is established. As a key implication, the integrodifferential equations governing the elastostatic problem of an inflected elastic slender beam resting on a displacement-driven nonlocal integral foundation are replaced with much simpler differential equations supplemented with kinematic, static, and new constitutive boundary conditions. The proposed nonlocal approach is illustrated by examining and analytically solving exemplar problems of structural engineering. Benchmark solutions for numerical analyses are also detected.
Plasticity and Deformation Mechanisms of Ultrafine-Grained Ti in Necking Region Revealed by Digital Image Correlation Technique
Authors: Zhao Yonghao , Gu Yanglin , Guo Yazhou
Published: February 2021

The conventional engineering stress-strain curve could not accurately describe the true stress-strain and local deformability of the necking part of tensile specimens, as it calculates the strain by using the whole gauge length, assuming the tensile specimen was deformed uniformly. In this study, we employed 3D optical measuring digital image correlation (DIC) to systematically measure the full strain field and local strain during the whole tensile process, and calculate the real-time strain and actual flow stress in the necking region of ultrafine-grained (UFG) Ti. The post-necking elongation and strain hardening exponent of the UFG Ti necking part were then measured as 36% and 0.101, slightly smaller than those of the coarse grained Ti (52% and 0.167), suggesting the high plastic deformability in the necking part of the UFG Ti. Finite elemental modeling (FEM) indicates that when necking occurs, strain is concentrated in the necking region. The stress state of the necking part was transformed from uniaxial in the uniform elongation stage to a triaxial stress state. A scanning electron microscopic (SEM) study revealed the shear and ductile fracture, as well as numerous micro shear bands in the UFG Ti, which are controlled by cooperative grain boundary sliding. Our work revealed the large plastic deformability of UFG metals in the necking region under a complex stress state.
Room Temperature Nanoencapsulation of Bioactive Eicosapentaenoic Acid Rich Oil within Whey Protein Microparticles
Authors: Escobar-García Juan David , Prieto Cristina , Pardo-Figuerez Maria , Lagaron Jose M.
Published: February 2021

In this study, emulsion electrospraying assisted by pressurized gas (EAPG) has been performed for the first time to entrap ca. 760 nm droplets of the bioactive eicosapentaenoic acid (EPA)-rich oil into whey protein concentrate (WPC) at room temperature. The submicron droplets of EPA oil were encapsulated within WPC spherical microparticles, with sizes around 5 µm. The EPA oil did not oxidize in the course of the encapsulation performed at 25 °C and in the presence of air, as corroborated by the peroxide value measurements. Attenuated Total Reflection—Fourier Transform Infrared spectroscopy and oxygen consumption tests confirmed that the encapsulated EPA-rich oil showed increased oxidative stability in comparison with the free oil during an accelerated oxidation test under ultraviolet light. Moreover, the encapsulated EPA-rich oil showed increased thermal stability in comparison with the free oil, as measured by oxidative thermogravimetric analysis. The encapsulated EPA-rich oil showed a somewhat reduced organoleptic impact in contrast with the neat EPA oil using rehydrated powdered milk as a reference. Finally, the oxidative stability by thermogravimetric analysis and organoleptic impact of mixtures of EPA and docosahexaenoic acid (DHA)-loaded microparticles was also studied, suggesting an overall reduced organoleptic impact compared to pure EPA. The results here suggest that it is possible to encapsulate 80% polyunsaturated fatty acids (PUFAs)-enriched oils by emulsion EAPG technology at room temperature, which could be used to produce personalized nutraceuticals or pharmaceuticals alone or in combination with other microparticles encapsulating different PUFAs to obtain different targeted health and organoleptic benefits.
Laser Nanostructuring for Diffraction Grating Based Surface Plasmon-Resonance Sensors
Authors: Gnilitskyi Iaroslav , Mamykin Sergii , Lanara Christina , Hevko Ihor , Dusheyko Mykhaylo , Bellucci Stefano , Stratakis Emmanuel
Published: February 2021

The surface plasmon resonance properties of highly regular laser-induced periodic surface structures (HR-LIPSSs) on Si, functionalized with Au nanoparticles (NPs), were investigated. In particular, the spectral dependencies of polarized light reflectance at various angles of incidence were measured and discussed. It is found that the deposition of Au NPs on such periodically textured substrates leads to significant enhancement of the plasmon resonance properties, compared to that measured on planar ones. This effect can be used to improve the efficiency of localized-plasmon-resonance-based sensors.
Preconditioning with Short-Term Dietary Restriction Attenuates Cardiac Oxidative Stress and Hypertrophy Induced by Chronic Pressure Overload
Authors: Kobara Miyuki , Naseratun Nessa , Toba Hiroe , Nakata Tetsuo
Published: February 2021

Left ventricular (LV) hypertrophy and associated heart failure are becoming a more prevalent and critical public health issue with the aging of society, and are exacerbated by reactive oxygen species (ROS). Dietary restriction (DR) markedly inhibits senescent changes; however, prolonged DR is difficult. We herein investigated whether preconditioning with short-term DR attenuates chronic pressure overload-induced cardiac hypertrophy and associated oxidative stress. Male c57BL6 mice were randomly divided into an ad libitum (AL) diet or 40% restricted diet (DR preconditioning, DRPC) group for 2 weeks prior to ascending aortic constriction (AAC), and all mice were fed ad libitum after AAC surgery. Two weeks after surgery, pressure overload by AAC increased LV wall thickness in association with LV diastolic dysfunction and promoted myocyte hypertrophy and cardiac fibrosis in the AL+AAC group. Oxidative stress in cardiac tissue and mitochondria also increased in the AL+AAC group in association with increments in cardiac NADPH oxidase-derived and mitochondrial ROS production. LV hypertrophy and associated cardiac dysfunction and oxidative stress were significantly attenuated in the DRPC+AAC group. Moreover, less severe mitochondrial oxidative damage in the DRPC+AAC group was associated with the suppression of mitochondrial permeability transition and cardiac apoptosis. These results indicate that chronic pressure overload-induced cardiac hypertrophy in association with cardiac and mitochondrial oxidative damage were attenuated by preconditioning with short-term DR.
Effect of a Low-Glycemic Load Diet Intervention on Maternal and Pregnancy Outcomes in Obese Pregnant Women
Authors: Goletzke Janina , De Haene Jessica , Stotland Naomi E. , Murphy Elizabeth J. , Perez-Rodriguez Marcela , King Janet C.
Published: February 2021

The increased prevalence of obese, pregnant women who have a higher risk of glucose intolerance warrants the need for nutritional interventions to improve maternal glucose homeostasis. In this study, the effect of a low-glycemic load (GL) (n = 28) was compared to a high-GL (n = 34) dietary intervention during the second half of pregnancy in obese women (body mass index (BMI) > 30 or a body fat >35%). Anthropometric and metabolic parameters were assessed at baseline (20 week) and at 28 and 34 weeks gestation. For the primary outcome 3h-glucose-iAUC (3h-incremental area under the curve), mean between-group differences were non-significant at every study timepoint (p = 0.6, 0.3, and 0.8 at 20, 28, and 34 weeks, respectively) and also assessing the mean change over the study period (p = 0.6). Furthermore, there was no statistically significant difference between the two intervention groups for any of the other examined outcomes (p ≥ 0.07). In the pooled cohort, there was no significant effect of dietary GL on any metabolic or anthropometric outcome (p ≥ 0.2). A post hoc analysis comparing the study women to a cohort of overweight or obese pregnant women who received only routine care showed that the non-study women were more likely to gain excess weight (p = 0.046) and to deliver large-for-gestational-age (LGA) (p = 0.01) or macrosomic (p = 0.006) infants. Thus, a low-GL diet consumed during the last half of pregnancy did not improve pregnancy outcomes in obese women, but in comparison to non-study women, dietary counseling reduced the risk of adverse outcomes.
What Is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?
Authors: Šíma Martin , Michaličková Danica , Slanař Ondřej
Published: February 2021

Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on phenobarbital pharmacokinetics in neonates and to identify its possible covariates suitable for individualization of initial drug dosing. Several covariates have been considered: body weight and height, body surface area, gestational and postnatal age, laboratory parameters of renal and hepatic functions, asphyxia, therapeutic hypothermia, extracorporeal membrane oxygenation (ECMO), drug interactions, and genetic polymorphisms. The most frequently studied and well-founded covariate for the estimation of phenobarbital dosing is actual body weight. Loading dose of 15–20 mg/kg followed by a maintenance dose of 3–5 mg/kg/day seems to be accurate. However, the evidence for the other covariates with respect to dosing individualization is not sufficient. Doses at the lower limit of suggested range should be preferred in patients with severe asphyxia, while the upper limit of the range should be targeted in neonates receiving ECMO support.
Drug Repurposing in the COVID-19 Era: Insights from Case Studies Showing Pharmaceutical Peculiarities
Authors: Gatti Milo , De Ponti Fabrizio
Published: February 2021

COVID-19 may lead to severe respiratory distress syndrome and high risk of death in some patients. So far (January 2021), only the antiviral remdesivir has been approved, although no significant benefits in terms of mortality and clinical improvement were recently reported. In a setting where effective and safe treatments for COVID-19 are urgently needed, drug repurposing may take advantage of the fact that the safety profile of an agent is already well known and allows rapid investigation of the efficacy of potential treatments, at lower costs and with reduced risk of failure. Furthermore, novel pharmaceutical formulations of older agents (e.g., aerosolized administration of chloroquine/hydroxychloroquine, remdesivir, heparin, pirfenidone) have been tested in order to increase pulmonary delivery and/or antiviral effects of potentially active drugs, thus overcoming pharmacokinetic issues. In our review, we will highlight the importance of the drug repurposing strategy in the context of COVID-19, including regulatory and ethical aspects, with a specific focus on novel pharmaceutical formulations and routes of administration.
Co-Delivery of Berberine Chloride and Tariquidar in Nanoliposomes Enhanced Intracellular Berberine Chloride in a Doxorubicin-Resistant K562 Cell Line Due to P-gp Overexpression
Authors: Vanti Giulia , Coronnello Marcella , Bani Daniele , Mannini Antonella , Bergonzi Maria Camilla , Bilia Anna Rita
Published: February 2021

The MDR phenomenon has become a major obstacle in the treatment of cancers, and among the strategies to reverse it, the inhibition of P-gp function and expression is essential to increase for effective anticancer drugs. In the present paper, the co-delivery of berberine chloride and tariquidar loaded nanoliposomes was investigated with the aim of enhancing solubility and improving desired effects for the antineoplastic drug and the P-gp inhibitor. Developed nanoliposomes were loaded with the electron-dense enzyme horseradish peroxidase, and analyzed by TEM to investigate their ability to enter in both K562 and K562/DOXO cell lines. Receptor-mediated endocytosis was evidenced for both cell lines. Nanoliposomes were loaded with tariquidar, berberine chloride, or both, maintaining chemical and physical characteristics—i.e., size, homogeneity, and encapsulation efficiency—and high suitability for parenteral administration. Tariquidar was able to reverse the MDR in the K562/DOXO cell line. Tariquidar- and berberine chloride-loaded nanoliposomes showed a significant increase of berberine chloride accumulation in tumor cells, which could be correlated with resensitization of the resistant cells to the antitumor agent. These results suggest that the co-delivery of the P-gp inhibitor, tariquidar, and the cytotoxicity inducer, berberine chloride, looks like a promising approach to overcome the MDR.
Educational Methods and Technological Innovations for Introductory Experiential Learning Given the Contact-Related Limitations Imposed by the SARS-CoV2/COVID-19 Pandemic
Authors: Reynolds Paul M. , Rhein Erica , Nuffer Monika , Gleason Shaun E.
Published: February 2021

Background: Acute respiratory syndrome related coronavirus disease (COVID-19) has led to substantial changes in pharmacy curricula, including the ability to provide in-person introductory experiential practice experiences (IPPEs) to University of Colorado’s International-Trained PharmD (ITPD) students. Methods: The IPPE course for ITPD students was redesigned to offer remote educational activities in the health system setting and simulated practice and communication activities in the community setting. Students were evaluated via surveys regarding the perceived value of these changes, and changes in knowledge, skills and abilities before and after activities. Results: A total of 6 students were enrolled in the revised IPPE course. Students agreed or strongly agreed that the overall distance-based IPPE experience, the remote health system activities, and the community activities were valuable. Students also strongly agreed that course design successfully met course outcomes and was relevant to pharmacy practice. In terms of knowledge, skills and abilities, numeric improvements were observed in remote health system activities and community-based simulated patient interactions, but results were not statistically significant. A high baseline level of knowledge led to minimal improvements in perceptions of improvement in community pharmacy skills regarding pharmacy simulation software. Conclusion: Implementation of distance-based IPPE activities may be an alternate educational modality.
Salinity Effect on Germination and Further Development of Parasitic Cuscuta spp. and Related Non-Parasitic Vines
Authors: Zagorchev Lyuben , Atanasova Alexandra , Pachedjieva Kalina , Tosheva Anita , Li Junmin , Teofanova Denitsa
Published: February 2021

Plants are continuously subjected to the unfavorable impact of abiotic stress factors, of which soil salinity is among the most adverse. Although away from direct soil contact throughout most of their lifecycle, stem parasitic plants of the genus Cuscuta, family Convolvulaceae are also affected by salinity. The present study aimed to assess salt stress impact on germination and early establishment of three Cuscuta species, in comparison to related nonparasitic vines of the same family. It was found, that Cuscuta spp. are highly sensitive to NaCl concentration within the range of 200 mM. Germination was delayed in time and reduced by nearly 70%, accompanied by decrease in further seedling growth, ability to infect host plants and growth rate of established parasites. The nonparasitic vines showed similar sensitivity to salinity at germination level, but appeared to adapt better after the stress factor was removed. However, the negative effect of salinity did not fully prevent some of the Cuscuta species from infecting hosts, probably a beneficial characteristic at a species level, allowing the parasite to successfully thrive under the scarce host availability under saline conditions.
Graphene-Polymer Composites
Authors: Pinto Artur M. , Magalhães Fernão D.
Published: February 2021

Graphene-polymer nanocomposites continue to gain interest in diverse scientific and technological fields [...]
Doxorubicin Loaded PLGA Nanoparticle with Cationic/Anionic Polyelectrolyte Decoration: Characterization, and Its Therapeutic Potency
Authors: Tsai Li-Hui , Yen Chia-Hsiang , Hsieh Hao-Ying , Young Tai-Horng
Published: February 2021

Optimized Doxorubicin hydrochloride (DOX) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (DPN) were prepared by controlling the water/oil distribution of DOX at different pH solutions and controlling the electrostatic interaction between DOX and different terminated-end PLGAs. Furthermore, cationic polyethylenimine (PEI) and anionic poly (acrylic acid) (PAA) were alternately deposited on DPN surface to form PEI-DPN (IDPN) and PAA-PEI-DPN (AIDPN) to enhance cancer therapy potency. Compared to DPN, IDPN exhibited a slower release rate in physiological conditions but PEI was demonstrated to increase the efficiency of cellular uptake and endo/lysosomal escape ability. AIDPN, with the outermost negatively charged PAA layer, still retained better endo/lysosomal escape ability compared to DPN. In addition, AIDPN exhibited the best pH-dependent release profile with 1.6 times higher drug release in pH 5.5 than in pH 7.4. Therefore, AIDPN with the characteristics of PEI and PAA simultaneously was the most optional cancer therapy choice within these three PLGA nanoparticles. As the proposed nanoparticles integrated optimal procedure factors, and possessed cationic and anionic outlayer, our drug delivery nanoparticles can provide an alternative solution to current drug delivery technologies.
Highly Thermal Conductive and Electrical Insulating Epoxy Composites with a Three-Dimensional Filler Network by Sintering Silver Nanowires on Aluminum Nitride Surface
Authors: Lee Wondu , Kim Jooheon
Published: February 2021

In this study, a new fabrication technique for three-dimensional (3D) filler networks was employed for the first time to prepare thermally conductive composites. A silver nanowire (AgNW)– aluminum nitride (AlN) (AA) filler was produced by a polyol method and hot-pressed in mold to connect the adjacent fillers by sintering AgNWs on the AlN surface. The sintered AA filler formed a 3D network, which was subsequently impregnated with epoxy (EP) resin. The fabricated EP/AA 3D network composite exhibited a perpendicular direction thermal conductivity of 4.49 W m−1 K−1 at a filler content of 400 mg (49.86 vol.%) representing an enhancement of 1973% with respect to the thermal conductivity of neat EP (0.22 W m−1 K−1). Moreover, the EP/AA decreased the operating temperature of the central processing unit (CPU) from 86.2 to 64.6 °C as a thermal interface material (TIM). The thermal stability was enhanced by 27.28% (99 °C) and the composites showed insulating after EP infiltration owing to the good insulation properties of AlN and EP. Therefore, these fascinating thermal and insulating performances have a great potential for next generation heat management application.
TEGDMA (Triethylene Glycol Dimethacrylate) Induces Both Caspase-Dependent and Caspase-Independent Apoptotic Pathways in Pulp Cells
Authors: Lovász Bálint Viktor , Berta Gergely , Lempel Edina , Sétáló György , Vecsernyés Mónika , Szalma József
Published: February 2021

Monomers leached from resin-based composites (RBCs) may reach intrapulpal concentrations of the millimolar (mM) range, which could contribute to inflammation. The aim of this investigation was to assess the cytotoxicity of triethylene glycol dimethacrylate (TEGDMA) monomers on pulp cells as well as to identify molecular mechanisms leading to apoptosis. Pulp cells were harvested from molars extracted for orthodontic reasons and cultured through an explant method. To assess cytotoxicity, cells underwent a 5-day exposure to 0.75, 1.5, and 3 mM TEGDMA and were subject to cell counting and WST-1 staining. Based on the findings, cells were subsequently exposed to 0.1, 0.2, 0.75, 1.5, and 3 mM TEGDMA for 24 h to uncover the details of apoptosis. Changes in the production or cleavage of the apoptosis-specific proteins caspase-8, caspase-9, caspase-3, caspase-12, and Apoptosis-Inducing Factor (AIF) were measured by Western blot. The 5-day study showed concentration- and time-dependent cytotoxicity. Significant cell death was detected after 24 h with TEGDMA concentrations of 1.5 and 3 mM. One-day exposure to TEGDMA led to the activation of caspase-8, -9, -3, and -12 and an increased AIF production. Results suggest that relevant concentrations of TEGDMA monomers, leached from RBCs, induce apoptosis in pulp cells through both caspase-dependent as well as caspase-independent mechanisms. Endoplasmic reticulum stress and the activation of caspase-independent apoptotic pathways may be further mechanisms by which monomers induce apoptosis in pulp cells.
Effect of Nanofiller Content on Dynamic Mechanical and Thermal Properties of Multi-Walled Carbon Nanotube and Montmorillonite Nanoclay Filler Hybrid Shape Memory Epoxy Composites
Authors: Mat Yazik Muhamad Hasfanizam , Sultan Mohamed Thariq Hameed , Jawaid Mohammad , Abu Talib Abd Rahim , Mazlan Norkhairunnisa , Md Shah Ain Umaira , Safri Syafiqah Nur Azrie
Published: February 2021

The aim of the present study has been to evaluate the effect of hybridization of montmorillonite (MMT) and multi-walled carbon nanotubes (MWCNT) on the thermal and viscoelastic properties of shape memory epoxy polymer (SMEP) nanocomposites. In this study, ultra-sonication was utilized to disperse 1%, 3%, and 5% MMT in combination with 0.5%, 1%, and 1.5% MWCNT into the epoxy system. The fabricated SMEP hybrid nanocomposites were characterized via differential scanning calorimetry, dynamic mechanical analysis, and thermogravimetric analysis. The storage modulus (E’), loss modulus (E”), tan δ, decomposition temperature, and decomposition rate, varied upon the addition of the fillers. Tan δ indicated a reduction of glass transition temperature (Tg) for all the hybrid SMEP nanocomposites. 3% MMT/1% MWCNT displayed best overall performance compared to other hybrid filler concentrations and indicated a better mechanical property compared to neat SMEP. These findings open a way to develop novel high-performance composites for various potential applications, such as morphing structures and actuators, as well as biomedical devices.
Non-Isothermal Thermogravimetry of Selected Tropical Woods and Their Degradation under Fire Using Cone Calorimetry
Authors: Makovicka Osvaldova Linda , Janigova Ivica , Rychly Jozef
Published: February 2021

For selected tropical woods (Cumaru, Garapa, Ipe, Kempas, Merbau), a relationship was established between non-isothermal thermogravimetry runs and the wood weight loss under flame during cone calorimetry flammability testing. A correlation was found for the rate constants for decomposition of wood in air at 250 and 300 °C found from thermogravimetry and the total time of sample burning related to the initial mass. Non-isothermal thermogravimetry runs were assumed to be composed from 3 theoretical runs such as decomposition of wood into volatiles itself, oxidation of carbon residue, and the formation of ash. A fitting equation of three processes was proposed and the resulting theoretical lines match experimental lines.
Preparation, Properties, and Microbial Impact of Tungsten (VI) Oxide and Zinc (II) Oxide Nanoparticles Enriched Polyethylene Sebacate Nanocomposites
Authors: Ismail Amr S. , Tawfik Salah M. , Mady Amr H. , Lee Yong-Ill
Published: February 2021

Nanoparticles of tungsten oxide (WO3) and zinc oxide (ZnO) enriched polyethylene sebacate (PES) nanocomposites were prepared through the coprecipitation process and condensation polymerization reaction. The obtained nano-sized particles of WO3 and ZnO, PES, and nanocomposites (WO3-PES NC and ZnO-PES NC) were investigated. The average molecular weight of the cured PES was measured by employing the gel permeation chromatography (GPC) technique. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) spectra assured the formation of the polymeric nanocomposites.WO3 and ZnO nanoparticles supposed a condensed porous spherical phase found implanted in the polymer structure, as detected by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) methods. These nano-scale systems achieved an electrical activity based on the conductive nanoparticles embedded matrix as a result of the ion–ion interactions. The microbial influence of the nanocomposites was examined against pathogenic bacteria; Pseudomonas aeruginosa,Escherichia coli, Staphylococcus aureus, and Bacillus subtilis, and Fungi; Aspergillus niger, and Candidaalbicans. Results exhibited that these nanocomposites have antimicrobial effects from moderate to slightly high on bacteria and high on fungi which was confirmed by a clear zone of inhibition. This study contributes to the design of reasonable composites to be under evaluation for their catalytic effect.
Thermodynamics and Machine Learning Based Approaches for Vapor–Liquid–Liquid Phase Equilibria in n-Octane/Water, as a Naphtha–Water Surrogate in Water Blends
Authors: Lopez-Zamora Sandra , Kong Jeonghoon , Escobedo Salvador , Lasa Hugo de
Published: February 2021

The prediction of phase equilibria for hydrocarbon/water blends in separators, is a subject of considerable importance for chemical processes. Despite its relevance, there are still pending questions. Among them, is the prediction of the correct number of phases. While a stability analysis using the Gibbs Free Energy of mixing and the NRTL model, provide a good understanding with calculation issues, when using HYSYS V9 and Aspen Plus V9 software, this shows that significant phase equilibrium uncertainties still exist. To clarify these matters, n-octane and water blends, are good surrogates of naphtha/water mixtures. Runs were developed in a CREC vapor–liquid (VL_Cell operated with octane–water mixtures under dynamic conditions and used to establish the two-phase (liquid–vapor) and three phase (liquid–liquid–vapor) domains. Results obtained demonstrate that the two phase region (full solubility in the liquid phase) of n-octane in water at 100 °C is in the 10−4 mol fraction range, and it is larger than the 10−5 mol fraction predicted by Aspen Plus and the 10−7 mol fraction reported in the technical literature. Furthermore, and to provide an effective and accurate method for predicting the number of phases, a machine learning (ML) technique was implemented and successfully demonstrated, in the present study.
Simplified Reactor Design for Mixed Culture-Based Electrofermentation toward Butyric Acid Production
Authors: Paiano Paola , Premier Giuliano , Guwy Alan , Kaur Amandeep , Michie Iain , Majone Mauro , Villano Marianna
Published: February 2021

Mixed microbial culture (MMC) electrofermentation (EF) represents a promising tool to drive metabolic pathways toward the production of a specific compound. Here, the MMC-EF process has been exploited to obtain butyric acid in simplified membrane-less reactors operated by applying a difference of potential between two low-cost graphite electrodes. Ten values of voltage difference, from −0.60 V to −1.5 V, have been tested and compared with the experiment under open circuit potential (OCP). In all the tested conditions, an enhancement in the production rate of butyric acid (from a synthetic mixture of glucose, acetate, and ethanol) was observed, ranging from 1.3- to 2.7-fold relative to the OCP. Smaller enhancements in the production rate resulted in higher values of the calculated specific energy consumption. However, at all applied voltages, a low flow of current was detected in the one-chamber reactors, accounting for an average value of approximately −100 µA. These results hold a substantial potential with respect to the scalability of the electrofermentation technology, since they pinpoint the possibility to control MMC-based bioprocesses by simply inserting polarized electrodes into traditional fermenters.
Experimental and Modeling of Dicamba Adsorption in Aqueous Medium Using MIL-101(Cr) Metal-Organic Framework
Authors: Isiyaka Hamza Ahmad , Jumbri Khairulazhar , Sambudi Nonni Soraya , Lim Jun Wei , Saad Bahruddin , Ramli Anita , Zango Zakariyya Uba
Published: February 2021

Drift deposition of emerging and carcinogenic contaminant dicamba (3,6-dichloro-2-methoxy benzoic acid) has become a major health and environmental concern. Effective removal of dicamba in aqueous medium becomes imperative. This study investigates the adsorption of a promising adsorbent, MIL-101(Cr) metal-organic framework (MOF), for the removal of dicamba in aqueous solution. The adsorbent was hydrothermally synthesized and characterized using N2 adsorption-desorption isotherms, Brunauer, Emmett and Teller (BET), powdered X-ray diffraction (XRD), Fourier Transformed Infrared (FTIR) and field emission scanning electron microscopy (FESEM). Adsorption models such as kinetics, isotherms and thermodynamics were studied to understand details of the adsorption process. The significance and optimization of the data matrix, as well as the multivariate interaction of the adsorption parameters, were determined using response surface methodology (RSM). RSM and artificial neural network (ANN) were used to predict the adsorption capacity. In each of the experimental adsorption conditions used, the ANN gave a better prediction with minimal error than the RSM model. The MIL-101(Cr) adsorbent was recycled six times to determine the possibility of reuse. The results show that MIL-101(Cr) is a very promising adsorbent, in particular due to the high surface area (1439 m2 g−1), rapid equilibration (~25 min), high adsorption capacity (237.384 mg g−1) and high removal efficiency of 99.432%.