bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antimicrobial Peptide Gramicidin S Enhances Membrane Adsorption and Ion Pore Formation Potency of Chemotherapy Drugs in Lipid Bilayers
Authors: Ashrafuzzaman Md.
Published: March 2021

We recently published two novel findings where we found the chemotherapy drugs (CDs) thiocolchicoside (TCC) and taxol to induce toroidal type ion pores and the antimicrobial peptide gramicidin S (GS) to induce transient defects in model membranes. Both CD pores and GS defects were induced under the influence of an applied transmembrane potential (≈100 mV), which was inspected using the electrophysiology record of membrane currents (ERMCs). In this article, I address the regulation of the membrane adsorption and pore formation of CDs due to GS-induced possible alterations of lipid bilayer physical properties. In ERMCs, low micromolar (≥1 μM) GS concentrations in the aqueous phase were found to cause an induction of defects in lipid bilayers, but nanomolar (nM) concentration GS did nothing. For the binary presence of CDs and GS in the membrane-bathing aqueous phase, the TCC pore formation potency is found to increase considerably due to nM concentration GS in buffer. This novel result resembles our recently reported finding that due to the binary aqueous presence of two AMPs (gramicidin A or alamethicin and GS), the pore or defect-forming potency of either AMP increases considerably. To reveal the underlying molecular mechanisms, the influence of GS (0–400 nM) on the quantitative liposome (membrane) adsorption of CD molecules, colchicine and TCC, was tested. I used the recently patented direct detection method, which helps detect the membrane active agents directly at the membrane in the mole fraction relative to its concentrations in aqueous phase. We find that GS, at concentrations known to do nothing to the lipid bilayer electrical barrier properties in ERMCs, increases the membrane adsorption (membrane uptake) of CDs considerably. This phenomenological finding along with the GS effects on CD-induced membrane conductance increase helps predict an important conclusion. The binary presence of AMPs alongside CDs in the lipid membrane vicinity may work toward enhancing the physical adsorption and pore formation potency of CDs in lipid bilayers. This may help understand why CDs cause considerable cytotoxicity.
The Nanoscopic Organization of Synapse Structures: A Common Basis for Cell Communication
Authors: Yang Xiaojuan , Annaert Wim
Published: March 2021

Synapse structures, including neuronal and immunological synapses, can be seen as the plasma membrane contact sites between two individual cells where information is transmitted from one cell to the other. The distance between the two plasma membranes is only a few tens of nanometers, but these areas are densely populated with functionally different proteins, including adhesion proteins, receptors, and transporters. The narrow space between the two plasma membranes has been a barrier for resolving the synaptic architecture due to the diffraction limit in conventional microscopy (~250 nm). Various advanced super-resolution microscopy techniques, such as stimulated emission depletion (STED), structured illumination microscopy (SIM), and single-molecule localization microscopy (SMLM), bypass the diffraction limit and provide a sub-diffraction-limit resolving power, ranging from 10 to 100 nm. The studies using super-resolution microscopy have revealed unprecedented details of the nanoscopic organization and dynamics of synaptic molecules. In general, most synaptic proteins appear to be heterogeneously distributed and form nanodomains at the membranes. These nanodomains are dynamic functional units, playing important roles in mediating signal transmission through synapses. Herein, we discuss our current knowledge on the super-resolution nanoscopic architecture of synapses and their functional implications, with a particular focus on the neuronal synapses and immune synapses.
A Collaborative Deprescribing Intervention in a Subacute Medical Outpatient Clinic: A Pilot Randomized Controlled Trial
Authors: Aharaz Anissa , Rasmussen Jens Henning , McNulty Helle Bach Ølgaard , Cyron Arne , Fabricius Pia Keinicke , Bengaard Anne Kathrine , Sejberg Hayley Rose Constance , Simonsen Rikke Rie Løvig , Treldal Charlotte , Houlind Morten Baltzer
Published: March 2021

Medication deprescribing is essential to prevent inappropriate medication use in multimorbid patients. However, experience of deprescribing in Danish Subacute Medical Outpatient Clinics (SMOCs) is limited. The objective of our pilot study was to evaluate the feasibility and sustainability of a collaborative deprescribing intervention by a pharmacist and a physician to multimorbid patients in a SMOC. A randomized controlled pilot study was conducted, with phone follow-up at 30 and 365+ days. A senior pharmacist performed a systematic deprescribing intervention using the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, the Danish deprescribing list, and patient interviews. A senior physician received the proposed recommendations and decided which should be implemented. The main outcome was the number of patients having ≥1 medication where deprescribing status was sustained 30 days after inclusion. Out of 76 eligible patients, 72 (95%) were included and 67 (93%) completed the study (57% male; mean age 73 years; mean number of 10 prescribed medications). Nineteen patients (56%) in the intervention group and four (12%) in the control group had ≥1 medication where deprescribing status was sustained 30 days after inclusion (p = 0.015). In total, 37 medications were deprescribed in the intervention group and five in the control group. At 365+ days after inclusion, 97% and 100% of the deprescribed medications were sustained in the intervention and control groups, respectively. The three most frequently deprescribed medication groups were analgesics, cardiovascular, and gastrointestinal medications. In conclusion, a collaborative deprescribing intervention for multimorbid patients was feasible and resulted in sustainable deprescribing of medication in a SMOC.
LDH and PDH Activities in the Ischemic Brain and the Effect of Reperfusion—An Ex Vivo MR Study in Rat Brain Slices Using Hyperpolarized [1-13C]Pyruvate
Authors: Sapir Gal , Shaul David , Lev-Cohain Naama , Sosna Jacob , Gomori Moshe J. , Katz-Brull Rachel
Published: March 2021

Ischemic stroke is a leading cause for neurologic disability worldwide, for which reperfusion is the only available treatment. Neuroimaging in stroke guides treatment, and therefore determines the clinical outcome. However, there are currently no imaging biomarkers for the status of the ischemic brain tissue. Such biomarkers could potentially be useful for guiding treatment in patients presenting with ischemic stroke. Hyperpolarized 13C MR of [1-13C]pyruvate is a clinically translatable method used to characterize tissue metabolism non-invasively in a relevant timescale. The aim of this study was to utilize hyperpolarized [1-13C]pyruvate to investigate the metabolic consequences of an ischemic insult immediately during reperfusion and upon recovery of the brain tissue. The rates of lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) were quantified by monitoring the rates of [1-13C]lactate and [13C]bicarbonate production from hyperpolarized [1-13C]pyruvate. 31P NMR of the perfused brain slices showed that this system is suitable for studying ischemia and recovery following reperfusion. This was indicated by the levels of the high-energy phosphates (tissue viability) and the chemical shift of the inorganic phosphate signal (tissue pH). Acidification, which was observed during the ischemic insult, has returned to baseline level following reperfusion. The LDH/PDH activity ratio increased following ischemia, from 47.0 ± 12.7 in the control group (n = 6) to 217.4 ± 121.3 in the ischemia-reperfusion group (n = 6). Following the recovery period (ca. 1.5 h), this value had returned to its pre-ischemia (baseline) level, suggesting the LDH/PDH enzyme activity ratio may be used as a potential indicator for the status of the ischemic and recovering brain.
A Label-Free Liquid Crystal Biosensor Based on Specific DNA Aptamer Probes for Sensitive Detection of Amoxicillin Antibiotic
Authors: Nguyen Duy , Jang Chang-Hyun
Published: March 2021

We developed a liquid crystal (LC) aptamer biosensor for the sensitive detection of amoxicillin (AMX). The AMX aptamer was immobilized onto the surface of a glass slide modified with a mixed self-assembled layer of dimethyloctadecyl [3-(trimethoxysilyl) propyl] ammonium chloride (DMOAP) and (3-aminopropyl) triethoxysilane (APTES). The long alkyl chains of DMOAP maintained the LC molecules in a homeotropic orientation and induced a dark optical appearance under a polarized light microscope (POM). In the presence of AMX, the specific binding of the aptamer and AMX molecules induced a conformational change in the aptamers, leading to the disruption of the homeotropic orientation of LCs, resulting in a bright optical appearance. The developed aptasensor showed high specificity and a low detection limit of 3.5 nM. Moreover, the potential application of the developed aptasensor for the detection of AMX in environmental samples was also demonstrated. Therefore, the proposed aptasensor is a promising platform for simple, rapid, and label-free monitoring of AMX in an actual water environment with high selectivity and sensitivity.
Defining the Human-Biota Thresholds of Toxicological Concern for Organic Chemicals in Freshwater: The Proposed Strategy of the LIFE VERMEER Project Using VEGA Tools
Authors: Baderna Diego , Faoro Roberta , Selvestrel Gianluca , Troise Adrien , Luciani Davide , Andres Sandrine , Benfenati Emilio
Published: March 2021

Several tons of chemicals are released every year into the environment and it is essential to assess the risk of adverse effects on human health and ecosystems. Risk assessment is expensive and time-consuming and only partial information is available for many compounds. A consolidated approach to overcome this limitation is the Threshold of Toxicological Concern (TTC) for assessment of the potential health impact and, more recently, eco-TTCs for the ecological aspect. The aim is to allow a safe assessment of substances with poor toxicological characterization. Only limited attempts have been made to integrate the human and ecological risk assessment procedures in a “One Health” perspective. We are proposing a strategy to define the Human-Biota TTCs (HB-TTCs) as concentrations of organic chemicals in freshwater preserving both humans and ecological receptors at the same time. Two sets of thresholds were derived: general HB-TTCs as preliminary screening levels for compounds with no eco- and toxicological information, and compound-specific HB-TTCs for chemicals with known hazard assessment, in terms of Predicted No effect Concentration (PNEC) values for freshwater ecosystems and acceptable doses for human health. The proposed strategy is based on freely available public data and tools to characterize and group chemicals according to their toxicological profiles. Five generic HB-TTCs were defined, based on the ecotoxicological profiles reflected by the Verhaar classes, and compound-specific thresholds for more than 400 organic chemicals with complete eco- and toxicological profiles. To complete the strategy, the use of in silico models is proposed to predict the required toxicological properties and suitable models already available on the VEGAHUB platform are listed.
Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques
Authors: Gjuroski Ilche , Furrer Julien , Vermathen Martina
Published: March 2021

Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis. In addition, both naturally derived as well as synthetic porphyrinic compounds are extensively explored for biomedical and technical applications such as photodynamic therapy (PDT) or photovoltaic systems, respectively. Their unique electronic structures and photophysical properties make this class of compounds so interesting for the multiple functions encountered. It is therefore not surprising that optical methods are typically the prevalent analytical tool applied in characterization and processes involving porphyrinic compounds. However, a wealth of complementary information can be obtained from NMR spectroscopic techniques. Based on the advantage of providing structural and dynamic information with atomic resolution simultaneously, NMR spectroscopy is a powerful method for studying molecular interactions between porphyrinic compounds and macromolecules. Such interactions are of special interest in medical applications of porphyrinic photosensitizers that are mostly combined with macromolecular carrier systems. The macromolecular surrounding typically stabilizes the encapsulated drug and may also modify its physical properties. Moreover, the interaction with macromolecular physiological components needs to be explored to understand and control mechanisms of action and therapeutic efficacy. This review focuses on such non-covalent interactions of porphyrinic drugs with synthetic polymers as well as with biomolecules such as phospholipids or proteins. A brief introduction into various NMR spectroscopic techniques is given including chemical shift perturbation methods, NOE enhancement spectroscopy, relaxation time measurements and diffusion-ordered spectroscopy. How these NMR tools are used to address porphyrin–macromolecule interactions with respect to their function in biomedical applications is the central point of the current review.
Production of Pyracantha Polysaccharide-Iron(III) Complex and Its Biologic Activity
Authors: Li Wan-Fen , Ma Hao-Hai , Yuan Shuai , Zhang Xi-Feng
Published: March 2021

In this study, the optimum synthetic process of the Pyracantha polysaccharide-iron (PPI) complex was studied via response surface methodology (RSM). Its antioxidant and anti-cancer activities were also investigated. It was demonstrated that the optimal conditions for the synthetic process of the complex were as follows: a pH of 8.9, a reaction temperature of 70 °C and a trisodium citrate:polysaccharide ratio of 1:2. PPI were analysis by UV, FTIR, SEM, CD, XRD, TGA and NMR. PPI was able to scavenge the metal ion, ABTS and free radicals of the superoxide anion, demonstrating its potential antioxidant activity. PPI was found to display cytotoxicity to Skov3 cells, as shown by its ability to induce apoptosis and alter gene expression in Skov3 cells. These findings show than PPI may represent a novel antioxidant and chemotherapeutic drug.
Prediction of Lap Shear Strength and Impact Peel Strength of Epoxy Adhesive by Machine Learning Approach
Authors: Kang Haisu , Lee Ji Hee , Choe Youngson , Lee Seung Geol
Published: March 2021

In this study, an artificial neural network (ANN), which is a machine learning (ML) method, is used to predict the adhesion strength of structural epoxy adhesives. The data sets were obtained by testing the lap shear strength at room temperature and the impact peel strength at −40 °C for specimens of various epoxy adhesive formulations. The linear correlation analysis showed that the content of the catalyst, flexibilizer, and the curing agent in the epoxy formulation exhibited the highest correlation with the lap shear strength. Using the analyzed data sets, we constructed an ANN model and optimized it with the selection set and training set divided from the data sets. The obtained root mean square error (RMSE) and R2 values confirmed that each model was a suitable predictive model. The change of the lap shear strength and impact peel strength was predicted according to the change in the content of components shown to have a high linear correlation with the lap shear strength and the impact peel strength. Consequently, the contents of the formulation components that resulted in the optimum adhesive strength of epoxy were obtained by our prediction model.
Simple Synthesis of Molybdenum Carbides from Molybdenum Blue Nanoparticles
Authors: Gavrilova Natalia , Myachina Maria , Nazarov Victor , Skudin Valery
Published: March 2021

In recent years, much attention has been paid to the development of a new flexible and variable method for molybdenum carbide (Mo2C) synthesis. This work reports the applicability of nano-size clusters of molybdenum blue to molybdenum carbide production by thermal treatment of molybdenum blue xerogels in an inert atmosphere. The method developed made it possible to vary the type (glucose, hydroquinone) and content of the organic reducing agent (molar ratio R/Mo). The effect of these parameters on the phase composition and specific surface area of molybdenum carbides and their catalytic activity was investigated. TEM, UV–VIS spectroscopy, DTA, SEM, XRD, and nitrogen adsorption were performed to characterize nanoparticles and molybdenum carbide. The results showed that, depending on the synthesis conditions, variants of molybdenum carbide can be formed: α-Mo2C, η-MoC, or γ-MoC. The synthesized samples had a high specific surface area (7.1–203.0 m2/g) and meso- and microporosity. The samples also showed high catalytic activity during the dry reforming of methane. The proposed synthesis method is simple and variable and can be successfully used to obtain both Mo2C-based powder and supports catalysts.
Effect of Polyvinyl Alcohol Ligands on Supported Gold Nano-Catalysts: Morphological and Kinetics Studies
Authors: Scurti Stefano , Monti Eleonora , Rodríguez-Aguado Elena , Caretti Daniele , Cecilia Juan Antonio , Dimitratos Nikolaos
Published: March 2021

The effect of polyvinyl alcohol (PVA) stabilizers and gold nanoparticles supported on active carbon (AuNPs/AC) was investigated in this article. Polymers with different molecular weights and hydrolysis degrees have been synthesized and used, like the stabilizing agent of Au nano-catalysts obtained by the sol-immobilization method. The reduction of 4-nitrophenol with NaBH4 has been used as a model reaction to investigate the catalytic activity of synthesized Au/AC catalysts. In addition, we report several characterization techniques such as ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) in order to correlate the properties of the polymer with the metal nanoparticle size and the catalytic activity. A volcano plot was observed linking the catalytic performance with hydrolysis degree and the maximum of the curve was identified at a value of 60%. The Au:PVA-60 weight ratio was changed in order to explain how the amount of the polymer can influence catalytic properties. The effect of nitroaromatic ring substituents on the catalytic mechanism was examined by the Hammett theory. Moreover, the reusability of the catalyst was investigated, with little to no decrease in activity observed over five catalytic cycles. Morphological and kinetic studies reported in this paper reveal the effect of the PVA polymeric stabilizer properties on the size and catalytic activity of supported gold nanoparticles.
Preliminary Study on Pasta Samples Characterized in Antioxidant Compounds and Their Biological Activity on Kidney Cells
Authors: Di Marco Federico , Trevisani Francesco , Vignolini Pamela , Urciuoli Silvia , Salonia Andrea , Montorsi Francesco , Romani Annalisa , Vago Riccardo , Bettiga Arianna
Published: March 2021

Pasta is one of the basic foods of the Mediterranean diet and for this reason it was chosen for this study to evaluate its antioxidant properties. Three types of pasta were selected: buckwheat, rye and egg pasta. Qualitative–quantitative characterization analyses were carried out by HPLC-DAD to identify antioxidant compounds. The data showed the presence of carotenoids such as lutein and polyphenols such as indoleacetic acid, (carotenoids from 0.08 to 0.16 mg/100 g, polyphenols from 3.7 to 7.4 mg/100 g). To assess the effect of the detected metabolites, in vitro experimentation was carried out on kidney cells models: HEK-293 and MDCK. Standards of β-carotene, indoleacetic acid and caffeic acid, hydroalcoholic and carotenoid-enriched extracts from samples of pasta were tested in presence of antioxidant agent to determine viability variations. β-carotene and indoleacetic acid standards exerted a protective effect on HEK-293 cells while no effect was detected on MDCK. The concentrations tested are likely in the range of those reached in body after the consumption of a standard pasta meal. Carotenoid-enriched extracts and hydroalcoholic extracts showed different effects, observing rescues for rye pasta hydroalcoholic extract and buckwheat pasta carotenoid-enriched extract, while egg pasta showed milder dose depending effects assuming pro-oxidant behavior at high concentrations. The preliminary results suggest behaviors to be traced back to the whole phytocomplexes respect to single molecules and need further investigations.
Does Flavonoid Consumption Improve Exercise Performance? Is It Related to Changes in the Immune System and Inflammatory Biomarkers? A Systematic Review of Clinical Studies since 2005
Authors: Ruiz-Iglesias Patricia , Gorgori-González Abril , Massot-Cladera Malén , Castell Margarida , Pérez-Cano Francisco J.
Published: March 2021

Flavonoids are attracting increasing attention due to their antioxidant, cardioprotective, and immunomodulatory properties. Nevertheless, little is known about their role in exercise performance in association with immune function. This systematic review firstly aimed to shed light on the ergogenic potential of flavonoids. A search strategy was run using SCOPUS database. The returned studies were screened by prespecified eligibility criteria, including intervention lasting at least one week and performance objectively quantified, among others. Fifty-one studies (54 articles) met the inclusion criteria, involving 1288 human subjects, either physically untrained or trained. Secondly, we aimed to associate these studies with the immune system status. Seventeen of the selected studies (18 articles) assessed changes in the immune system. The overall percentage of studies reporting an improved exercise performance following flavonoid supplementation was 37%, the proportion being 25% when considering quercetin, 28% for flavanol-enriched extracts, and 54% for anthocyanins-enriched extracts. From the studies reporting an enhanced performance, only two, using anthocyanin supplements, focused on the immune system and found certain anti-inflammatory effects of these flavonoids. These results suggest that flavonoids, especially anthocyanins, may exert beneficial effects for athletes’ performances, although further studies are encouraged to establish the optimal dosage and to clarify their impact on immune status.
Relative Validity of MijnEetmeter: A Food Diary App for Self-Monitoring of Dietary Intake
Authors: Ocké Marga , Dinnissen Ceciel , Stafleu Annette , de Vries Jeanne , van Rossum Caroline
Published: March 2021

This study aimed to evaluate the relative validity of intake of energy, nutrients and food groups assessed with MijnEetmeter food diary as compared to 24-h dietary recalls, and if this differed between experienced and new users. One hundred men and women aged 18–70 y participated, of whom 47 had prior experience with the tool. Participants kept MijnEetmeter on three days. Trained dietitians called them three times for a 24-h dietary recall interview, once recalling food consumption on the same day as the food recording in MijnEetmeter. Systematic differences and correlations were assessed, and Bland–Altman plots were created; both for 3-day mean intakes and for intakes on the same day. Relative to 24-h dietary recalls, MijnEetmeter underestimated consumption of drinks, added fat, cereal products, and potatoes. Relative underestimation was observed for energy intake (6%) and about half of the nutrients. Experienced MijnEetmeter users underestimated intake the least. For intake of energy and six key nutrients, correlations between 3-day mean intakes were above 0.7 except for sodium intake. In conclusion, MijnEetmeter moderately underestimates intakes of energy and some nutrients and food groups. To improve the self-monitoring of dietary intake, it is recommended that the users record food consumption for several days and that the apps probes for easily forgotten foods and drinks.
The Association between Australian Childcare Centre Healthy Eating Practices and Children’s Healthy Eating Behaviours: A Cross-Sectional Study within Lunchbox Centres
Authors: Barnes Courtney , Yoong Sze Lin , Wolfenden Luke , Nathan Nicole , Wedesweiler Taya , Kerr Jayde , Pearson Nicole , Grady Alice
Published: March 2021

The association between healthy eating practices and child dietary intake in childcare centres where parents pack foods from home has received little attention. This study aimed to: (1) Describe the nutritional content of foods and beverages consumed by children in care; and (2) Assess the association between centre healthy eating practices and child intake of fruit and vegetable servings, added sugar(grams), saturated fat(grams) and sodium(milligrams) in care. A cross-sectional study amongst 448 children attending 22 childcare centres in New South Wales, Australia, was conducted. Child dietary intake was measured via weighed lunchbox measurements, photographs and researcher observation, and centre healthy eating practices were assessed via researcher observation of centre nutrition environments. Children attending lunchbox centres consumed, on average 0.80 servings (standard deviation 0.69) of fruit and 0.27 servings (standard deviation 0.51) of vegetables in care. The availability of foods within children’s lunchboxes was associated with intake of such foods (p < 0.01). Centre provision of intentional healthy eating learning experiences (estimate −0.56; p = 0.01) and the use of feeding practices that support children’s healthy eating (estimate −2.02; p = 0.04) were significantly associated with reduced child intake of saturated fat. Interventions to improve child nutrition in centres should focus on a range of healthy eating practices, including the availability of foods packed within lunchboxes.
Investigations of Olive Oil Industry By-Products Extracts with Potential Skin Benefits in Topical Formulations
Authors: Nunes Andreia , Gonçalves Lídia , Marto Joana , Martins Ana Margarida , Silva Alexandra N. , Pinto Pedro , Martins Marta , Fraga Carmo , Ribeiro Helena Margarida
Published: March 2021

The by-products of olive oil industry are a major ecological issue due to their phenolic content, highly toxic organic load, and low pH. However, they can be recovered and reused, since their components have antioxidant, anti-inflammatory, and photoprotector properties. In this work, oil-in-water creams containing three different olive oil industry by-products extracts were produced without the use of organic solvents. First, the extracts were thoroughly characterized in vitro for cytotoxicity, inhibition of skin enzymes, and antioxidant and photoprotection capacities. Safety studies were then performed, including ocular and skin irritation tests, ecotoxicity evaluation, and in vivo Human Repeat Insult Patch Test. The results obtained in this initial characterization supported the incorporation of the extracts in the cream formulations. After preparation, the creams were characterized for their organoleptic, physicochemical, droplet size and rheological properties, and microbial contamination. The results showed that all formulations were semi-solid creams, with stable pH, compatible with the skin, without microbial contamination, and with the expected droplet size range. The rheological analysis showed shear-thinning behavior with yield stress, with the viscosity decreasing with increasing shear rate. The oscillatory results suggest that the creams have a strong network structure, being easily rubbed into the skin. Finally, compatibility, acceptability and antioxidant efficacy were evaluated in vivo, in human volunteers. No adverse reactions were observed after application of the formulations on skin and the cream with the highest concentrations of phenolic compounds showed the highest antioxidant efficiency. In conclusion, the results suggest that olive oil industry by-products extracts have valuable properties that favor their re-use in the cosmetic industry. The example presented here showed their successful incorporation into creams and their impact in these formulations’ appearance, pH, and rheological performance, as well as their in vivo compatibility with skin and antioxidant efficiency.
Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology
Authors: Sabo Amelia-Naomi , Jannier Sarah , Becker Guillaume , Lessinger Jean-Marc , Entz-Werlé Natacha , Kemmel Véronique
Published: March 2021

Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K/AkT/mTor pathway has stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with other antineoplastic agents. However, in cancer, there is no consensus on sirolimus TDM. In the RAPIRI phase I trial, the combination sirolimus + irinotecan was evaluated as a new treatment for refractory pediatric cancers. Blood sampling at first sirolimus intake (D1) and at steady state (D8), followed by LC/MS2 analysis, was used to develop a population pharmacokinetic model (Monolix® software). A mono-compartmental model with first-order absorption and elimination best fit the data. The only covariate retained for the final model was “body surface area” (D1 and D8). The model also demonstrated that 1.5 mg/m2 would be the recommended sirolimus dose for further studies and that steady-state TDM is necessary to adjust the dosing regimen in atypical profiles (36.4% of the population). No correlation was found between sirolimus trough concentrations and efficacy and/or observed toxicities. The study reveals the relevance of sirolimus TDM in pediatric oncology as it is needed in organ transplantation.
Silicon in the Soil–Plant Continuum: Intricate Feedback Mechanisms within Ecosystems
Authors: Katz Ofir , Puppe Daniel , Kaczorek Danuta , Prakash Nagabovanalli B. , Schaller Jörg
Published: March 2021

Plants’ ability to take up silicon from the soil, accumulate it within their tissues and then reincorporate it into the soil through litter creates an intricate network of feedback mechanisms in ecosystems. Here, we provide a concise review of silicon’s roles in soil chemistry and physics and in plant physiology and ecology, focusing on the processes that form these feedback mechanisms. Through this review and analysis, we demonstrate how this feedback network drives ecosystem processes and affects ecosystem functioning. Consequently, we show that Si uptake and accumulation by plants is involved in several ecosystem services like soil appropriation, biomass supply, and carbon sequestration. Considering the demand for food of an increasing global population and the challenges of climate change, a detailed understanding of the underlying processes of these ecosystem services is of prime importance. Silicon and its role in ecosystem functioning and services thus should be the main focus of future research.
Physiological Responses of Salinized Fenugreek (Trigonellafoenum-graecum L.) Plants to Foliar Application of Salicylic Acid
Authors: Abdelhameed Reda E. , Abdel Latef Arafat Abdel Hamed , Shehata Rania S.
Published: March 2021

Considering the detrimental effects of salt stress on the physiological mechanisms of plants in terms of growth, development and productivity, intensive efforts are underway to improve plant tolerance to salinity. Hence, an experiment was conducted to assess the impact of the foliar application of salicylic acid (SA; 0.5 mM) on the physiological traits of fenugreek (Trigonellafoenum-graecum L.) plants grown under three salt concentrations (0, 75, and 150 mM NaCl). An increase in salt concentration generated a decrease in the chlorophyll content index (CCI); however, the foliar application of SA boosted the CCI. The malondialdehyde content increased in salt-stressed fenugreek plants, while a reduction in content was observed with SA. Likewise, SA application induced an accumulation of proline, total phenolics, and flavonoids. Moreover, further increases in total free amino acids and shikimic acid were observed with the foliar application of SA, in either control or salt-treated plants. Similar results were obtained for ascorbate peroxidase, peroxidase, polyphenol oxidase, and catalase with SA application. Hence, we concluded that the foliar application of SA ameliorates salinity, and it is a growth regulator that improves the tolerance of fenugreek plants under salt stress.
The Metabolite Profile in Culture Supernatant of Aster yomena Callus and Its Anti-Photoaging Effect in Skin Cells Exposed to UVB
Authors: Kim Woo Sik , Seo Jeong Hun , Lee Jae-In , Ko Eun-Sil , Cho Sang-Min , Kang Jea-Ran , Jeong Jong-Hoon , Jeong Yu Jeong , Kim Cha Young , Cha Jeong-Dan , Ryu Young-Bae
Published: March 2021

Aster yomena (A. yomena) extract has anti-inflammatory, antioxidant, anti-asthma, and anti-atopic effects. However, the commercial use of A. yomena extract requires a long processing time with specific processing steps (including heat treatment and ethanol precipitation), and there are various environmental problems. We aimed to build a system to produce A. yomena extract by culturing the callus in a bioreactor that can allow rapid process scale-up to test the effect of extract (AYC-CS-E) isolated from culture supernatant of A. yomena callus on photoaging of human keratinocytes (HaCaT) caused by ultraviolet B (UVB) exposure. Through screening analysis based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), 17 major metabolites were tentatively identified from AYC-CS-E for the first time. The suppression of cell proliferation caused by UVB was effectively alleviated in UVB-irradiated HaCaT cells treated with AYC-CS-E. Treatment with AYC-CS-E strongly induced the formation of type I procollagen and the inhibition of elastase in UVB-irradiated HaCaT cells and significantly reduced the expression of matrix metalloproteinase (MMP)-1. In addition, treatment of UVB-irradiated HaCaT cells with AYC-CS-E effectively improved various factors associated with an inflammatory reaction, skin damage recovery, skin moisture retention, and hyper-keratinization caused by photoaging, such as reactive oxygen species (ROS), pro-inflammatory cytokines, transforming growth factor beta (TGF-β), MMP-3, MMP-9, filaggrin, hyaluronic acid synthase 2 (HAS-2), keratin 1 (KRT-1), nuclear factor-kappa B (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2) at the gene and protein levels. These results suggest that AYC-CS-E can be used as a cosmetic ingredient for various skin diseases caused by photoaging, and the current callus culture system can be used commercially to supply cosmetic ingredients.
Characterization of Novel Biopolymer Blend Mycocel from Plant Cellulose and Fungal Fibers
Authors: Irbe Ilze , Filipova Inese , Skute Marite , Zajakina Anna , Spunde Karina , Juhna Talis
Published: March 2021

In this study unique blended biopolymer mycocel from naturally derived biomass was developed. Softwood Kraft (KF) or hemp (HF) cellulose fibers were mixed with fungal fibers (FF) in different ratios and the obtained materials were characterized regarding microstructure, air permeability, mechanical properties, and virus filtration efficiency. The fibers from screened Basidiomycota fungi Ganoderma applanatum (Ga), Fomes fomentarius (Ff), Agaricus bisporus (Ab), and Trametes versicolor (Tv) were applicable for blending with cellulose fibers. Fungi with trimitic hyphal system (Ga, Ff) in combinations with KF formed a microporous membrane with increased air permeability (>8820 mL/min) and limited mechanical strength (tensile index 9–14 Nm/g). HF combination with trimitic fungal hyphae formed a dense fibrillary net with low air permeability (77–115 mL/min) and higher strength 31–36 Nm/g. The hyphal bundles of monomitic fibers of Tv mycelium and Ab stipes made a tight structure with KF with increased strength (26–43 Nm/g) and limited air permeability (14–1630 mL/min). The blends KF FF (Ga) and KF FF (Tv) revealed relatively high virus filtration capacity: the log10 virus titer reduction values (LRV) corresponded to 4.54 LRV and 2.12 LRV, respectively. Mycocel biopolymers are biodegradable and have potential to be used in water microfiltration, food packaging, and virus filtration membranes.
Interfacial Doping Effects in Fluoropolymer-Tungsten Diselenide Composites Providing High-Performance P-Type Transistors
Authors: Lee Hyeonji , Hong Seongin , Yoo Hocheon
Published: March 2021

In this study, we investigated the p-doping effects of a fluoropolymer, Cytop, on tungsten diselenides (WSe2). The hole current of the Cytop–WSe2 field-effect transistor (FET) was boosted by the C–F bonds of Cytop having a strong dipole moment, enabling increased hole accumulation. Analysis of the observed p-doping effects using atomic force microscopy (AFM) and Raman spectroscopy shed light on the doping mechanism. Moreover, Cytop reduces the electrical instability by preventing the adsorption of ambient molecules on the WSe2 surface. Annealing Cytop deposited on WSe2 eliminated the possible impurities associated with adsorbates (i.e., moisture and oxygen) that act as traps on the surface of WSe2. After thermal annealing, the Cytop–WSe2 FET afforded higher p-type conductivity and reduced hysteresis. The combination of the Cytop–WSe2 FET with annealing provides a promising method for obtaining high-performance WSe2 p-type transistors.
Lignin Extraction from Waste Pine Sawdust Using a Biomass Derived Binary Solvent System
Authors: Magalhães Solange , Filipe Alexandra , Melro Elodie , Fernandes Catarina , Vitorino Carla , Alves Luís , Romano Anabela , Rasteiro Maria G. , Medronho Bruno
Published: March 2021

Lignocellulosic biomass fractionation is typically performed using methods that are somehow harsh to the environment, such as in the case of kraft pulping. In recent years, the development of new sustainable and environmentally friendly alternatives has grown significantly. Among the developed systems, bio-based solvents emerge as promising alternatives for biomass processing. Therefore, in the present work, the bio-based and renewable chemicals, levulinic acid (LA) and formic acid (FA), were combined to fractionate lignocellulosic waste (i.e., maritime pine sawdust) and isolate lignin. Different parameters, such as LA:FA ratio, temperature, and extraction time, were optimized to boost the yield and purity of extracted lignin. The LA:FA ratio was found to be crucial regarding the superior lignin extraction from the waste biomass. Moreover, the increase in temperature and extraction time enhances the amount of extracted residue but compromises the lignin purity and reduces its molecular weight. The electron microscopy images revealed that biomass samples suffer significant structural and morphological changes, which further suggests the suitability of the newly developed bio-fractionation process. The same was concluded by the FTIR analysis, in which no remaining lignin was detected in the cellulose-rich fraction. Overall, the novel combination of bio-sourced FA and LA has shown to be a very promising system for lignin extraction with high purity from biomass waste, thus contributing to extend the opportunities of lignin manipulation and valorization into novel added-value biomaterials.
Dissolution and Interaction of Cellulose Carbamate in NaOH/ZnO Aqueous Solutions
Authors: Kang Yanhui , Wang Fangyu , Zhang Zeming , Zhou Jinping
Published: March 2021

The dissolution and molecular interactions of cellulose carbamate (CC) in NaOH/ZnO aqueous solutions were studied using optical microscopy, differential scanning calorimetry (DSC), 1H NMR, dynamic light scattering (DLS), atomic force microscopy (AFM), transmission electron microscopy (TEM), and molecular dynamic simulation. The dissolution of CC in NaOH/ZnO aqueous solutions using the freezing–thawing method was an exothermic process, and the lower temperature was favorable for the dissolution of CC. ZnO dissolved in NaOH aqueous solutions with the formation of Zn(OH)42−, and no free Zn2+ ions existed in the solvents. NaOH/Na2Zn(OH)4 system formed strong interactions with the hydroxyl groups of CC to improve its solubility and the stability of CC solution. The results indicate that 7 wt% NaOH/1.6 wt% ZnO aqueous solution was the most appropriate solvent for the dissolution of CC. This work revealed the dissolution interaction of CC-NaOH/ZnO solutions, which is beneficial for the industrialization of the CarbaCell process.
Dentin Bond Integrity of Filled and Unfilled Resin Adhesive Enhanced with Silica Nanoparticles—An SEM, EDX, Micro-Raman, FTIR and Micro-Tensile Bond Strength Study
Authors: Alhenaki Aasem M. , Attar Esra A. , Alshahrani Abdullah , Farooq Imran , Vohra Fahim , Abduljabbar Tariq
Published: March 2021

The objective of this study was to synthesize and assess unfilled and filled (silica nanoparticles) dentin adhesive polymer. Methods encompassing scanning electron microscopy (SEM)—namely, energy dispersive X-ray spectroscopy (EDX), micro-tensile bond strength (µTBS) test, Fourier transform infrared (FTIR), and micro-Raman spectroscopy—were utilized to investigate Si particles’ shape and incorporation, dentin bond toughness, degree of conversion (DC), and adhesive–dentin interaction. The Si particles were incorporated in the experimental adhesive (EA) at 0, 5, 10, and 15 wt. % to yield Si-EA-0% (negative control group), Si-EA-5%, Si-EA-10%, and Si-EA-15% groups, respectively. Teeth were set to form bonded samples using adhesives in four groups for µTBS testing, with and without aging. Si particles were spherical shaped and resin tags having standard penetrations were detected on SEM micrographs. The EDX analysis confirmed the occurrence of Si in the adhesive groups (maximum in the Si-EA-15% group). Micro-Raman spectroscopy revealed the presence of characteristic peaks at 638, 802, and 1300 cm−1 for the Si particles. The µTBS test revealed the highest mean values for Si-EA-15% followed by Si-EA-10%. The greatest DC was appreciated for the control group trailed by the Si-EA-5% group. The addition of Si particles of 15 and 10 wt. % in dentin adhesive showed improved bond strength. The addition of 15 wt. % resulted in a bond strength that was superior to all other groups. The Si-EA-15% group demonstrated acceptable DC, suitable dentin interaction, and resin tag formation.
Bone Matrix Non-Collagenous Proteins in Tissue Engineering: Creating New Bone by Mimicking the Extracellular Matrix
Authors: Carvalho Marta S. , Cabral Joaquim M. S. , da Silva Cláudia L. , Vashishth Deepak
Published: March 2021

Engineering biomaterials that mimic the extracellular matrix (ECM) of bone is of significant importance since most of the outstanding properties of the bone are due to matrix constitution. Bone ECM is composed of a mineral part comprising hydroxyapatite and of an organic part of primarily collagen with the rest consisting on non-collagenous proteins. Collagen has already been described as critical for bone tissue regeneration; however, little is known about the potential effect of non-collagenous proteins on osteogenic differentiation, even though these proteins were identified some decades ago. Aiming to engineer new bone tissue, peptide-incorporated biomimetic materials have been developed, presenting improved biomaterial performance. These promising results led to ongoing research focused on incorporating non-collagenous proteins from bone matrix to enhance the properties of the scaffolds namely in what concerns cell migration, proliferation, and differentiation, with the ultimate goal of designing novel strategies that mimic the native bone ECM for bone tissue engineering applications. Overall, this review will provide an overview of the several non-collagenous proteins present in bone ECM, their functionality and their recent applications in the bone tissue (including dental) engineering field.
Near-Field Electrospinning and Melt Electrowriting of Biomedical Polymers—Progress and Limitations
Authors: King William , Bowlin Gary
Published: March 2021

Near-field electrospinning (NFES) and melt electrowriting (MEW) are the process of extruding a fiber due to the force exerted by an electric field and collecting the fiber before bending instabilities occur. When paired with precise relative motion between the polymer source and the collector, a fiber can be directly written as dictated by preprogrammed geometry. As a result, this precise fiber control results in another dimension of scaffold tailorability for biomedical applications. In this review, biomedically relevant polymers that to date have manufactured fibers by NFES/MEW are explored and the present limitations in direct fiber writing of standardization in published setup details, fiber write throughput, and increased ease in the creation of complex scaffold geometries are discussed.
3D Bioprinted Bacteriostatic Hyperelastic Bone Scaffold for Damage-Specific Bone Regeneration
Authors: Shokouhimehr Mohammadreza , Theus Andrea S. , Kamalakar Archana , Ning Liqun , Cao Cong , Tomov Martin L. , Kaiser Jarred M. , Goudy Steven , Willett Nick J. , Jang Ho Won , LaRock Christopher N. , Hanna Philip , Lechtig Aron , Yousef Mohamed , Martins Janaina Da Silva , Nazarian Ara , Harris Mitchel B. , Mahmoudi Morteza , Serpooshan Vahid
Published: March 2021

Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic bone (HB) implants, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), are 3D bioprinted and their regenerative effect on large non-healing bone fractures is studied. Scaffolds are bioprinted with the geometry that closely correspond to that of the bone defect, using an osteoconductive, highly elastic, surgically friendly bioink mainly composed of hydroxyapatite. Incorporation of SPIONs into HB bioink results in enhanced bacteriostatic properties of bone grafts while exhibiting no cytotoxicity. In vitro culture of mouse embryonic cells and human osteoblast-like cells remain viable and functional up to 14 days on printed HB scaffolds. Implantation of damage-specific bioprinted constructs into a rat model of femoral bone defect demonstrates significant regenerative effect over the 2-week time course. While no infection, immune rejection, or fibrotic encapsulation is observed, HB grafts show rapid integration with host tissue, ossification, and growth of new bone. These results suggest a great translational potential for 3D bioprinted HB scaffolds, laden with functional nanoparticles, for hard tissue engineering applications.