bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives
Authors: Noureddine Fatima Y. , Altara Raffaele , Fan Fan , Yabluchanskiy Andriy , Booz George W. , Zouein Fouad A.
Published: June 2020

The effects of the renin–angiotensin system (RAS) surpass the renal and cardiovascular systems to encompass other body tissues and organs, including the brain. Angiotensin II (Ang II), the most potent mediator of RAS in the brain, contributes to vascular dementia via different mechanisms, including neuronal homeostasis disruption, vascular remodeling, and endothelial dysfunction caused by increased inflammation and oxidative stress. Other RAS components of emerging significance at the level of the blood–brain barrier include angiotensin-converting enzyme 2 (ACE2), Ang(1–7), and the AT2, Mas, and AT4 receptors. The various angiotensin hormones perform complex actions on brain endothelial cells and pericytes through specific receptors that have either detrimental or beneficial actions. Increasing evidence indicates that the ACE2/Ang(1–7)/Mas axis constitutes a protective arm of RAS on the blood–brain barrier. This review provides an update of studies assessing the different effects of angiotensins on cerebral endothelial cells. The involved signaling pathways are presented and help highlight the potential pharmacological targets for the management of cognitive and behavioral dysfunctions associated with vascular dementia.
Various Anti-HSPA2 Antibodies Yield Different Results in Studies on Cancer-Related Functions of Heat Shock Protein A2
Authors: Scieglinska Dorota , Sojka Damian Robert , Gogler-Pigłowska Agnieszka , Chumak Vira , Krawczyk Zdzisław
Published: June 2020

Heat shock proteins (HSPs) constitute a major part of the molecular chaperone system and play a fundamental role in cell proteostasis. The HSPA (HSP70) family groups twelve highly homologous HSPA proteins. Certain HSPAs are regarded as important cancer-related proteins, prospective therapeutic targets for cancer treatment, and also as potential cancer biomarkers. Heat Shock Protein A2 (HSPA2), a testis-enriched chaperone and one of the least characterized members of the HSPA family, has recently emerged as an important cancer-relevant protein with potential biomarker significance. Nevertheless, conflicting conclusions have been recently drawn both according to HSPA2 role in cancer cells, as well as to its prognostic value. In this work we have shown that one of the serious limitations in HSPA2 protein research is cross-reactivity of antibodies marketed as specific for HSPA2 with one or more other HSPA(s). Among non-specific antibodies were also those recently used for HSPA2 detection in functional and biomarker studies. We showed how using non-specific antibodies can generate misleading conclusions on HSPA2 expression in non-stressed cancer cells and tumors, as well as in cancer cells exposed to proteotoxic stress. Our findings addressed concerns on some published studies dealing with HSPA2 as a cancer-related protein.
Reorganization Tips from a Sarcoma Unit at Time of the COVID-19 Pandemic in Italy: Early Experience from a Regional Referral Oncologic Center
Authors: Rossi Barbara , Zoccali Carmine , Baldi Jacopo , Scotto di Uccio Alessandra , Biagini Roberto , De Luca Assunta , Petrongari Maria Grazia , Ferraresi Virginia
Published: June 2020

Since the World Health Organization declared the novel coronavirus outbreak a global health emergency, Italy’s lockdown was declared on 9 March 2020. Elective orthopedic surgery was forced to stop to allow the healthcare system to face the emergency. However, many orthopedic oncology cases could not be postponed. The aim of this study was to report the experience in managing sarcoma patients and the reorganization of a cancer center in an attempt to maintain it free from COVID-19. A Coronavirus Crisis Unit was established by the health directorate coordination in order to adopt specific procedures. General rules of screening and social distancing were applied in different health settings (entrance check point, hospital inward, outpatient clinic, operative room). Regarding oncologic orthopedics, priority was given to bone and soft tissue sarcomas, metastases and aggressive benign tumors at risk of impending or pathologic fracture. Precise indications were followed to manage first outpatient visits, patients undergoing surgery and follow-up. Meticulous adherence to rules among patients and personnel and collaboration between leadership and medical staff in order to continue to perform multidisciplinary treatment protocols, maintain the availability of infrastructural spaces and source protective equipment, swabs and screening samples have been successful in the aim towards a safe cure for cancer patients.
Dynamic Scheduling and Communication System to Manage Last Mile Handovers
Authors: Paidi Vijay , Nyberg Roger , Håkansson Johan
Published: June 2020

Last mile handover is the most problematic phase in the delivery process, while real-time communication and dynamic scheduling are major problem areas associated with attended last mile handovers. These problem areas need to be addressed holistically to facilitate efficient last mile handovers. The aim of this paper is to report the design and functionalities of a decision-support system which holistically addresses these problem areas. The functionalities of decision-support system which addresses dynamic scheduling and real-time communication problem areas are discussed using case studies. We conclude that a holistic decision-support system with multiparty communication among the stakeholders facilitates improving customer satisfaction, business opportunities and reducing operational costs for logistics companies.
Experimental Investigation on the Fire Resistance of Glued-In Rod Timber Joints with Heat Resistant Modified Epoxy Resin
Authors: Luo Liquan , Shi Benkai , Liu Weiqing , Yang Huifeng , Ling Zhibin
Published: June 2020

This paper presents an experimental evaluation of the fire resistance of glued-in rod timber joints using epoxy resin, with and without modification. A heat-resistant modified resin was designed by adding inorganic additives into the epoxy resin, aiming to improve the heat resistance. Joints that were made using the modified epoxy resin at room temperature showed a bearing capacity comparable to those with commercial epoxy resin. Twenty-one joint specimens with the modified epoxy resin and six with a commercial epoxy resin were tested in a fire furnace to evaluate the fire resistance. The main failure mode was the pull-out of the rod, which is typical in fire tests of this type of joints. As to the effects of the test parameters, this study considered the effects of adhesive types, sectional sizes, stress levels, and fireproof coatings. The test results showed that the fire resistance period of a joint can be evidently improved by modifying the resin and using the fireproof coating, as the improvements reached 73% and 35%, respectively, compared with the joint specimens with commercial epoxy resin. It was also found that, for all specimens, the fire resistance period decreased with an increase in the stress level and increased with an increase in the sectional sizes.
Thermal Characteristics of Expandable Graphite–Wood Particle Composites
Authors: Chun Kwanok , Kim Jeonggon , Rie Dongho
Published: June 2020

According to the Fire Statistics Yearbook of the National Fire Agency of the Republic of Korea, the total number of fires in 2018 was 42,338, which resulted in 2500 victims and amounted to property damages of approximately 560 billion KRW. The number of fires in buildings where wood was used as a finishing material was 28,013 (66%) in that period. To minimize human and property damage, composite materials were prepared by mixing wood particles with expandable graphite. The physical and thermal properties of the composite materials were investigated. It was observed that the expansion rate increased by 341.7% according to the expandable graphite content. Additionally, the total heat released and the thermal conductivity decreased from 38.63 to 2.5 MJ/m2 and from 24.62 to 7.8 W/m·K. The time to inactivity of white mouse in the smoke toxicity test was 14.9 min and exceeded the toxicity standard for flame retardant performance. The expandable graphite added to composite materials adopted worm-like shapes as a result of combustion, and it formed a fine lattice layer structure with 16–22 μm gaps that could reduce thermal conductivity. In addition, we can minimize the damage to people and property in the event of a fire.
Residual Pulmonary Hypertension More than 20 Years after Repair of Shunt Lesions
Authors: Jančauskaitė Dovilė , Rudienė Virginija , Jakutis Gabrielius , Geenen Laurie W , Roos-Hesselink Jolien W , Gumbienė Lina
Published: June 2020

Background and Objectives: After successful surgical repair of a congenital shunt lesion, pulmonary hypertension (PH) often disappears. However, PH can persist long-term after the closure. This study aimed to assess the prevalence of PH long-term after surgical repair of congenital heart disease (CHD), and to evaluate the outcomes and preoperative factors related to residual PH. Materials and Methods: In this retrospective cohort study, we reviewed patients who underwent right heart catheterisation in Vilnius University Hospital Santaros Klinikos during the period of 1985–2007. Among 4118 right heart catheterisations performed, 160 patients underwent congenital systemic-to-pulmonary shunt repair at a young age (<18 years) and had pre-operative PH. Half of the patients were foreigners whose follow-up data were unavailable. Eventually, 88 patients with available follow-up data were included in this study. Results: The median age at diagnosis of CHD with PH was 0.8 (0.6–3.0) and 1.1 (0.6–3.9) years at surgery (50% females). Residual PH was assessed 9.5 years after surgery and observed in 30.7% (n = 27) of the patients. It was associated with having more than one shunt (44.4% (n = 12), p = 0.016) and higher median pulmonary vascular resistance (3.4 (2.5–6.5) vs. 2.2 (1.0–3.7), p = 0.035) at baseline. After a median follow-up of 21 (15–24) years, 9.1% of the patients were deceased. Kaplan–Meier survival analysis revealed significantly higher mortality in the residual PH group (p = 0.035). Conclusions: Residual PH affects a significant proportion of patients after surgical repair of a shunt lesion and is associated with worse long-term outcome.
Bioinformatics and Transcriptional Study of the Nramp Gene in the Extreme Acidophile Acidithiobacillus ferrooxidans Strain DC
Authors: Miao Bo , Shen Li , Liu Xueduan , Zeng Weimin , Wu Xueling
Published: June 2020

The family of Nramp (natural resistance-associated macrophage protein) metal ion transporter functions in diverse organisms from bacteria to humans. Acidithiobacillus ferrooxidans (At. ferrooxidans) is a Gram-negative bacterium that lives at pH 2 in high concentrations of soluble ferrous ion (600 mM). The AFE_2126 protein of At. ferrooxidans of the Dachang Copper Mine (DC) was analyzed by bioinformatics software or online tools, showing that it was highly homologous to the Nramp family, and its subcellular localization was predicted to locate in the cytoplasmic membrane. Transcriptional study revealed that AFE_2126 was expressed by Fe2+-limiting conditions in At. ferrooxidans DC. It can be concluded that the AFE_2126 protein may function in ferrous ion transport into the cells. Based on the ΔpH of the cytoplasmic membrane between the periplasm (pH 3.5) and the cytoplasm (pH 6.5), it can be concluded that Fe2+ is transported in the direction identical to that of the H+ gradient. This study indirectly confirmed that the function of Nramp in At. ferrooxidans DC can transport divalent iron ions.
Effects of L-Phenylalanine on Energy Intake and Glycaemia—Impacts on Appetite Perceptions, Gastrointestinal Hormones and Gastric Emptying in Healthy Males
Authors: Fitzgerald Penelope C. E. , Manoliu Benoit , Herbillon Benjamin , Steinert Robert E. , Horowitz Michael , Feinle-Bisset Christine
Published: June 2020

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g (‘Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by 13C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK (p = 0.01) and suppressed energy intake (p = 0.012); energy intake was correlated with stimulation of CCK (r = −0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = −0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose (p = 0.043) and peak plasma glucose (p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.
Anti-Pathogenic Functions of Non-Digestible Oligosaccharides In Vitro
Authors: Asadpoor Mostafa , Peeters Casper , Henricks Paul A. J. , Varasteh Soheil , Pieters Roland J. , Folkerts Gert , Braber Saskia
Published: June 2020

Non-digestible oligosaccharides (NDOs), complex carbohydrates that resist hydrolysis by salivary and intestinal digestive enzymes, fulfill a diversity of important biological roles. A lot of NDOs are known for their prebiotic properties by stimulating beneficial bacteria in the intestinal microbiota. Human milk oligosaccharides (HMOs) represent the first prebiotics that humans encounter in life. Inspired by these HMO structures, chemically-produced NDO structures (e.g., galacto-oligosaccharides and chito-oligosaccharides) have been recognized as valuable food additives and exert promising health effects. Besides their apparent ability to stimulate beneficial microbial species, oligosaccharides have shown to be important inhibitors of the development of pathogenic infections. Depending on the type and structural characteristics, oligosaccharides can exert a number of anti-pathogenic effects. The most described effect is their ability to act as a decoy receptor, thereby inhibiting adhesion of pathogens. Other ways of pathogenic inhibition, such as interference with pathogenic cell membrane and biofilm integrity and DNA transcription, are less investigated, but could be equally impactful. In this review, a comprehensive overview of In vitro anti-pathogenic properties of different NDOs and associated pathways are discussed. A framework is created categorizing all anti-pathogenic effects and providing insight into structural necessities for an oligosaccharide to exert one of these effects.
The Role of Selenium Mineral Trace Element in Exercise: Antioxidant Defense System, Muscle Performance, Hormone Response, and Athletic Performance. A Systematic Review
Authors: Fernández-Lázaro Diego , Fernandez-Lazaro Cesar I. , Mielgo-Ayuso Juan , Navascués Lourdes Jiménez , Córdova Martínez Alfredo , Seco-Calvo Jesús
Published: June 2020

Exercise overproduces oxygen reactive species (ROS) and eventually exceeds the body’s antioxidant capacity to neutralize them. The ROS produce damaging effects on the cell membrane and contribute to skeletal muscle damage. Selenium (Se), a natural mineral trace element, is an essential component of selenoproteins that plays an important role in antioxidant defense. The activity of the enzyme glutathione peroxidase (GPx), a highly-efficient antioxidant enzyme, is closely dependent on the presence of Se. These properties of Se may be potentially applicable to improve athletic performance and training recovery. We systematically searched for published studies to evaluate the effectiveness of Se supplementation on antioxidant defense system, muscle performance, hormone response, and athletic performance among physically active individuals. We used the Preferred Reporting Elements for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and searched in SCOPUS, Web of Science (WOS), and PubMed databases to identify published studies until March 2020. The systematic review incorporated original studies with randomized controlled crossover or parallel design in which intake of Se administered once a day was compared with the same placebo conditions. No exclusions were applied for the type of physical exercise performed, the sex, nor the age of the participants. Among 150 articles identified in the search, 6 met the criteria and were included in the systematic review. The methodological quality of the studies was evaluated using the McMaster Critical Review Form. Oral Se supplementation with 180 µg/day or 240 µg/day (selenomethionine) and 200 µg/day (Sodium Selenite), significantly decreased lipid hydroperoxide levels and increased GPx in plasma, erythrocyte, and muscle. No significant effects were observed on athletic performance, testosterone hormone levels, creatine kinase activity, and exercise training-induced adaptations on oxidative enzyme activities or on muscle fiber type myosin heavy chain expression. In addition, Se supplementation showed to have a dampening effect on the mitochondria changes in chronic and acute exercise. In summary, the use of Se supplementation has no benefits on aerobic or anaerobic athletic performance but it may prevent Se deficiencies among athletes with high-intensity and high-volume training. Optimal Se plasma levels may be important to minimize chronic exercise-induced oxidative effects and modulate the exercise effect on mitochondrial changes.
Uptake of Australia’s Health Star Rating System 2014–2019
Authors: Shahid Maria , Neal Bruce , Jones Alexandra
Published: June 2020

In June 2014, Australia and New Zealand adopted a voluntary front-of-pack nutrition label, the Health Star Rating (HSR) system. Our aim was to assess its uptake in Australia in the five years following adoption and examine the feasibility of proposed targets for future uptake. Numbers and proportions of products eligible to carry a HSR were recorded each year between 2014 and 2019 as part of an annual survey of four large Australian retail outlets. Uptake was projected to 2024. Mean HSR values were determined for products that were, and were not labelled with a HSR logo, and summary data presented overall, by HSR score, by major food category, by manufacturer and manufacturer group. Differences in mean HSR were assessed by independent samples t-test. HSR uptake continues to increase, appearing on 7118/17,477 (40.7%) of eligible products in 2019. Voluntary display of the HSR logo was increasing linearly at 6.8% annually. This would need to be maintained to reach 70% by 2024. Of those products displaying a HSR logo, more than three quarters (76.4%) had a HSR ≥ 3.0. Products displaying a HSR logo had a significantly higher mean HSR (3.4), compared to products not displaying a HSR logo (2.6) (p < 0.001). One hundred and thirty-nine manufacturers were using HSR, but retailers Coles, Woolworths and ALDI were together responsible for the majority of uptake (55.9%). Manufacturer members of the Australian Food and Grocery Council were responsible for 28.6% of uptake. Our findings illustrate the limits of commercial goodwill in applying HSR voluntarily. Ongoing implementation must pair clear targets and timelines for uptake with a firm pathway to make HSR mandatory if sufficient progress is not achieved.
Frontline Blinatumomab in Older Adults with Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia
Authors: Niyongere Sandrine , Sanchez-Petitto Gabriela , Masur Jack , Baer Maria R. , Duong Vu H. , Emadi Ashkan
Published: June 2020

Outcomes of acute lymphoblastic leukemia (ALL) in older adults treated with chemotherapy are poor. The CD19/CD3 bispecific T-cell engager (BiTE) antibody blinatumomab is approved for refractory, relapsed or minimal/measurable residual disease (MRD)-positive B-cell ALL, but there is little experience in the upfront setting, including in older patients. We retrospectively analyzed outcomes of blinatumomab monotherapy in five newly diagnosed Philadelphia chromosome-negative B-cell ALL patients over 70 years. Three had cytokine release syndrome, treated with dexamethasone and/or tocilizumab, and four patients had neurotoxicity, treated with dexamethasone, without blinatumomab interruption. All five achieved complete remission (CR) after cycle one, three with undetectable MRD. All five were alive at 8 to 15 months. Three remained in MRD-negative CR. Two relapsed after cycle 3, one with extramedullary disease. In our small cohort of patients over 70 years, blinatumomab was safe initial therapy and produced a high response rate.
Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies
Authors: Teixeira Maria Inês , Amaral Maria Helena , Costa Paulo C. , Lopes Carla M. , Lamprou Dimitrios A.
Published: June 2020

Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation.
Development of Antibody–Oligonucleotide Complexes for Targeting Exosomal MicroRNA
Authors: Yamayoshi Asako , Oyama Shota , Kishimoto Yusuke , Konishi Ryo , Yamamoto Tsuyoshi , Kobori Akio , Harada Hiroshi , Ashihara Eishi , Sugiyama Hiroshi , Murakami Akira
Published: June 2020

MicroRNAs in exosomes (exosomal miRNAs) are considered as significant targets for cancer therapy. Anti-miR oligonucleotides are often used for the functional inhibition of miRNAs; however, there are no studies regarding the regulation of exosomal miRNA functions. In this study, we attempted to develop a novel drug delivery system using anti-exosome antibody–anti-miR oligonucleotide complexes (ExomiR-Tracker) to hijack exosomes to carry anti-miR oligonucleotides inside exosome-recipient cells. We found that ExomiR-Tracker bound to the exosomes, and then the complexes were introduced into the recipient cells. We also found that anti-miR oligonucleotides introduced into the recipient cells can exhibit inhibitory effects on exosomal miRNA functions in vitro and in vivo. We believe that our strategy would be a promising one for targeting exosomal miRNAs.
The Role of Cocrystallization-Mediated Altered Crystallographic Properties on the Tabletability of Rivaroxaban and Malonic Acid
Authors: Kale Dnyaneshwar P. , Puri Vibha , Kumar Amit , Kumar Navin , Bansal Arvind K.
Published: June 2020

The present work aims to understand the crystallographic basis of the mechanical behavior of rivaroxaban-malonic acid cocrystal (RIV-MAL Co) in comparison to its parent constituents, i.e., rivaroxaban (RIV) and malonic acid (MAL). The mechanical behavior was evaluated at the bulk level by performing “out of die” bulk compaction and at the particle level by nanoindentation. The tabletability order for the three solids was MAL < RIV < RIV-MAL Co. MAL demonstrated “lower” tabletability because of its lower plasticity, despite it having reasonably good bonding strength (BS). The absence of a slip plane and “intermediate” BS contributed to this behavior. The “intermediate” tabletability of RIV was primarily attributed to the differential surface topologies of the slip planes. The presence of a primary slip plane (0 1 1) with flat-layered topology can favor the plastic deformation of RIV, whereas the corrugated topology of secondary slip planes (1 0 2) could adversely affect the plasticity. In addition, the higher elastic recovery of RIV crystal also contributed to its tabletability. The significantly “higher” tabletability of RIV-MAL Co among the three molecular solids was the result of its higher plasticity and BS. Flat-layered topology slip across the (0 0 1) plane, the higher degree of intermolecular interactions, and the larger separation between adjacent crystallographic layers contributed to improved mechanical behavior of RIV-MAL Co. Interestingly, a particle level deformation parameter H/E (i.e., ratio of mechanical hardness H to elastic modulus E) was found to inversely correlate with a bulk level deformation parameter σ0 (i.e., tensile strength at zero porosity). The present study highlighted the role of cocrystal crystallographic properties in improving the tabletability of materials.
Effect of Rumex Acetosa Extract, a Herbal Drug, on the Absorption of Fexofenadine
Authors: Ahn Jung Hwan , Kim Junhyeong , Rehman Naveed Ur , Kim Hye-Jin , Ahn Mi-Jeong , Chung Hye Jin
Published: June 2020

Herbal drugs are widely used for the auxiliary treatment of diseases. The pharmacokinetics of a drug may be altered when it is coadministered with herbal drugs that can affect drug absorption. The effects of herbal drugs on absorption must be evaluated. In this study, we investigated the effects of Rumex acetosa (R. acetosa) extract on fexofenadine absorption. Fexofenadine was selected as a model drug that is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide 1A2 (OATP1A2). Emodine—the major component of R. acetosa extract—showed P-gp inhibition in vitro and in vivo. Uptake of fexofenadine via OATP1A2 was inhibited by R. acetosa extract in OATP1A2 transfected cells. A pharmacokinetic study showed that the area under the plasma concentration–time curve (AUC) of fexofenadine was smaller in the R. acetosa extract coadministered group than in the control group. R. acetosa extract also decreased aqueous solubility of fexofenadine HCl. The results of this study suggest that R. acetosa extract could inhibit the absorption of certain drugs via intervention in the aqueous solubility and the drug transporters. Therefore, R. acetosa extract may cause drug interactions when coadministered with substrates of drug transporters and poorly water-soluble drugs, although further clinical studies are needed.
Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances
Authors: Bertoni Serena , Albertini Beatrice , Passerini Nadia
Published: June 2020

Delivery of poorly water soluble active pharmaceutical ingredients (APIs) by semi-crystalline solid dispersions prepared by spray congealing in form of microparticles (MPs) is an emerging method to increase their oral bioavailability. In this study, solid dispersions based on hydrophilic Gelucires® (Gelucire® 50/13 and Gelucire® 48/16 in different ratio) of three BCS class II model compounds (carbamazepine, CBZ, tolbutamide, TBM, and cinnarizine, CIN) having different physicochemical properties (logP, pKa, Tm) were produced by spray congealing process. The obtained MPs were investigated in terms of morphology, particles size, drug content, solid state properties, drug-carrier interactions, solubility, and dissolution performances. The solid-state characterization showed that the properties of the incorporated drug had a profound influence on the structure of the obtained solid dispersion: CBZ recrystallized in a different polymorphic form, TBM crystallinity was significantly reduced as a result of specific interactions with the carrier, while smaller crystals were observed in case of CIN. The in vitro tests suggested that the drug solubility was mainly influenced by carrier composition, while the drug dissolution behavior was affected by the API solid state in the MPs after the spray congealing process. Among the tested APIs, TBM-Gelucire dispersions showed the highest enhancement in drug dissolution as a result of the reduced drug crystallinity.
Evaluating the Therapeutic Efficacy of Mono- and Bivalent Affibody-Based Fusion Proteins Targeting HER3 in a Pancreatic Cancer Xenograft Model
Authors: Dahlsson Leitao Charles , S. Rinne Sara , Altai Mohamed , Vorontsova Olga , Dunås Finn , Jonasson Per , Tolmachev Vladimir , Löfblom John , Ståhl Stefan , Orlova Anna
Published: June 2020

Human epidermal growth factor receptor 3 (HER3) has been increasingly scrutinized as a potential drug target since the elucidation of its role in mediating tumor growth and acquired therapy resistance. Affibody molecules are so-called scaffold proteins with favorable biophysical properties, such as a small size for improved tissue penetration and extravasation, thermal and chemical stability, and a high tolerance to modifications. Additionally, affibody molecules are efficiently produced in prokaryotic hosts or by chemical peptide synthesis. We have previously evaluated the biodistribution profiles of five mono- and bivalent anti-HER3 affibody molecules (designated as 3) fused to an albumin-binding domain (designated as A), 3A, 33A, 3A3, A33, and A3, that inhibit ligand-dependent phosphorylation. In the present study, we examined the therapeutic efficacy of the three most promising variants, 3A, 33A, and 3A3, in a direct comparison with the HER3-targeting monoclonal antibody seribantumab (MM-121) in a preclinical BxPC-3 pancreatic cancer model. Xenografted mice were treated with either an affibody construct or MM-121 and the tumor growth was compared to a vehicle group. Receptor occupancy was estimated by positron emission tomography/computed tomography (PET/CT) imaging using a HER3-targeting affibody imaging agent [68Ga]Ga-(HE)3-Z08698-NODAGA. The affibody molecules could inhibit ligand-dependent phosphorylation and cell proliferation in vitro and demonstrated tumor growth inhibition in vivo comparable to that of MM-121. PET/CT imaging showed full receptor occupancy for all tested drug candidates. Treatment with 3A and 3A3 affibody constructs was more efficient than with 33A and similar to the anti-HER3 antibody seribantumab, showing that the molecular design of affibody-based therapeutics targeting HER3 in terms of the relative position of functional domains and valency has an impact on therapeutic effect.
Hura crepitans L. Extract: Phytochemical Characterization, Antioxidant Activity, and Nanoformulation
Authors: Vassallo Antonio , Armentano Maria Francesca , Miglionico Rocchina , Caddeo Carla , Chirollo Claudia , Gualtieri Maria Josefina , Ostuni Angela , Bisaccia Faustino , Faraone Immacolata , Milella Luigi
Published: June 2020

The purpose of this study was to improve the knowledge on Hura crepitans L., a plant belonging to the Euphorbiaceae family that, on the one hand, is known to be toxic, but on the other, is a source of polyphenols with health-promoting effects. Different green extraction methods were applied, varying solvent, temperature, and duration of extraction, which can influence the phytochemical profile and biological activity of plant extracts, and the extracts were fully characterized. Aqueous extracts exhibited a superior antioxidant activity, as indicated by different spectrophotometric tests, and were cytoprotective to HepG2 cells used as model cells. Liquid chromatography–mass spectrometry analyses were performed to identify the secondary metabolites involved in these effects and demonstrated that solvent, duration, and temperature indeed influenced the extraction of polyphenols. Furthermore, the most promising extract, in terms of antioxidant potential, was incorporated into liposomes with the aim of promoting cell interaction and enhancing the antioxidant activity.
Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs
Authors: Hellinen Laura , Bahrpeyma Sina , Rimpelä Anna-Kaisa , Hagström Marja , Reinisalo Mika , Urtti Arto
Published: June 2020

Interactions between drugs and melanin pigment may have major impacts on pharmacokinetics. Therefore, melanin binding can modify the efficacy and toxicity of medications in ophthalmic and other disease of pigmented tissues, such as melanoma. As melanin is present in many pigmented tissues in the human body, investigation of pigment binding is relevant in drug discovery and development. Conventionally, melanin binding assays have been performed using an equilibrium binding study followed by chemical analytics, such as LC/MS. This approach is laborious, relatively slow, and limited to facilities with high performance quantitation instrumentation. We present here a screening of melanin binding with label-free microscale thermophoresis (MST) that utilizes the natural autofluorescence of melanin. We determined equilibrium dissociation constants (Kd) of 11 model compounds with melanin nanoparticles. MST categorized the compounds into extreme (chloroquine, penicillin G), high (papaverine, levofloxacin, terazosin), intermediate (timolol, nadolol, quinidine, propranolol), and low melanin binders (atropine, methotrexate, diclofenac) and displayed good correlation with binding parameter values obtained with the conventional binding study and LC/MS analytics. Further, correlation was seen between predicted melanin binding in human retinal pigment epithelium and choroid (RPE-choroid) and Kd values obtained with MST. This method represents a useful and fast approach for classification of compounds regarding melanin binding. Thus, the method can be utilized in various fields, including drug discovery, pharmacokinetics, and toxicology.
Ecological and Geochemical Conditions for the Accumulation of Antioxidants in the Leaves of Lathyrus maritimus (L.) Bigel
Authors: Maslennikov Pavel , Golovina Elena , Artemenko Anastasia
Published: June 2020

The article explores how location affected the dynamics of accumulation of ascorbic acid (AC) and oxidized forms of AC—dehydroascorbic acid (DAA) and diketogulonic acid (DKGA) in beach pea during ontogenetic development. Our analysis focuses on research of the ecological and geochemical conditions growing of the plant on the Curonian Spit. The level of hydrogen peroxide and the activity of enzymes that break it down were analyzed. Antioxidant activity and the total concentration of phenolics were evaluated in the leaves of beach pea on the leeward and windward sides of the foredune. It was established that the level of AC, DAA, and DKGA was higher in the plants growing on the windward side of the foredune. A higher concentration of peroxy compounds, which stimulate the biosynthesis of antioxidant enzymes (catalase, ascorbate peroxidase), polyphenols, and other low molecular antioxidants (AOA) was observed in the leaves of these plants. The plants on the windward side enter phenological stages one or two weeks later than their counterparts on the leeward side of the foredune do. There was a generally negative correlation between the temperature of the soil and the accumulation of ascorbate system acids in the leaves of the studied plants (r = −0.46/(−0.68), p < 0.05). The accumulation of low molecular antioxidants and enzymes in beach pea suggests their adaptation to the adverse conditions of the windward side of the foredune.
Influence of Adding Offcuts and Trims with a Recycling Approach on the Properties of High-Density Fibrous Composites
Authors: Sala Conrad M. , Robles Eduardo , Kowaluk Grzegorz
Published: June 2020

The sizeable global production of wood-based products requires new sources of raw material, but also creates large quantities of wastes or composites that do not comply with requirements. In this study, the influence of different shares of recovered high-density fiberboards (HDF-r), reversed into the production, on industrial HDF properties, has been examined. HDF-r may be a suitable partial substitute for raw pinewood for industrial HDF production. Although most of the mechanical properties, as well as thickness swelling and water absorption, had a linear decrease with the increase in the share of HDF-r share, the elaborated boards met most of the commercial requirements (EN 622-5). The property that did not meet the requirements was the internal bond strength for panels with 10% of HDF-r. The presented results show that, after some adjustments, it should be possible to produce HDF boards with up to 10% of recycled HDF being able to meet all commercial requirements.
Fabrication of Self-Lubricating Porous UHMWPE with Excellent Mechanical Properties and Friction Performance via Rotary Sintering
Authors: Cao Xianwu , Li Yuping , He Guangjian
Published: June 2020

Porous ultra-high-molecular-weight polyethylene (UHMWPE) self-lubricating materials were designed and fabricated by a rotary sintering method, and the microstructure and properties were evaluated. Results showed that the rotary molding could not only significantly improve the molding efficiency but also formed uniform internal microstructures with high porosity, excellent mechanical properties, and low friction coefficient. Under oil lubricating conditions, the friction curve of samples quickly reached a steady state, the friction coefficient was reduced by 50%, and the repeat utilization was up to 99%. The following optimum sintering conditions were shown: Sintering temperature of 180 °C or 190 °C, sintering time determined as 10 min, and loading capacity of between 3.6 g and 3.8 g. Therefore, it is expected that this work will open a convenient and compatible strategy for fabricating porous materials with good self-lubricating performance.
Tough Polymer Gel Electrolytes for Aluminum Secondary Batteries Based on Urea: AlCl3, Prepared by a New Solvent-Free and Scalable Procedure
Authors: Miguel Álvaro , García Nuria , Gregorio Víctor , López-Cudero Ana , Tiemblo Pilar
Published: June 2020

Polymer gel electrolytes have been prepared with polyethylene oxide (PEO) and the deep eutectic mixture of AlCl3: urea (uralumina), a liquid electrolyte which has proved to be an excellent medium for the electrodeposition of aluminum. The polymer gel electrolytes are prepared by mixing PEO in the liquid electrolyte at T > 65 °C, which is the melting point of PEO. This procedure takes a few minutes and requires no subsequent evaporation steps, being a solvent-free, and hence more sustainable procedure as compared to solvent-mediated ones. The absence of auxiliary solvents and evaporation steps makes their preparation highly reproducible and easy to scale up. PEO of increasing molecular weight (Mw = 1 × 105, 9 × 105, 50 × 105 and 80 × 105 g mol−1), including an ultra-high molecular weight (UHMW) polymer, has been used. Because of the strong interactions between the UHMW PEO and uralumina, self-standing gels can be produced with as little as 2.5 wt% PEO. These self-standing polymer gels maintain the ability to electrodeposit and strip aluminum, and are seen to retain a significant fraction of the current provided by the liquid electrolyte. Their gels’ rheology and electrochemistry are stable for months, if kept under inert atmosphere, and their sensitivity to humidity is significantly lower than that of liquid uralumina, improving their stability in the event of accidental exposure to air, and hence, their safety. These polymer gels are tough and thermoplastic, which enable their processing and molding into different shapes, and their recyclability and reprocessability. Their thermoplasticity also allows the preparation of concentrated batches (masterbatch) for a posteriori dilution or additive addition. They are elastomeric (rubbery) and very sticky, which make them very robust, easy to manipulate and self-healing.
Solar Cells for Indoor Applications: Progress and Development
Authors: Biswas Swarup , Kim Hyeok
Published: June 2020

The Internet of things (IoT) has been rapidly growing in the past few years. IoT connects numerous devices, such as wireless sensors, actuators, and wearable devices, to optimize and monitor daily activities. Most of these devices require power in the microwatt range and operate indoors. To this end, a self-sustainable power source, such as a photovoltaic (PV) cell, which can harvest low-intensity indoor light, is appropriate. Recently, the development of highly efficient PV cells for indoor applications has attracted tremendous attention. Therefore, different types of PV materials, such as inorganic, dye-sensitized, organic, and perovskite materials, have been employed for harvesting low-intensity indoor light energy. Although considerable efforts have been made by researchers to develop low-cost, stable, and efficient PV cells for indoor applications, Extensive investigation is necessary to resolve some critical issues concerning PV cells, such as environmental stability, lifetime, large-area fabrication, mechanical flexibility, and production cost. To address these issues, a systematic review of these aspects will be highly useful to the research community. This study discusses the current status of the development of indoor PV cells based on previous reports. First, we have provided relevant background information. Then, we have described the different indoor light sources, and subsequently critically reviewed previous reports regarding indoor solar cells based on different active materials such as inorganic, dye-sensitized, organic, and perovskite. Finally, we have placed an attempt to provide insight into factors needed to further improve the feasibility of PV technology for indoor applications.
Preserving Softness and Elastic Recovery in Silicone-Based Stretchable Electrodes Using Carbon Nanotubes
Authors: Bannych Andrey , Katz Sari , Barkay Zahava , Lachman Noa
Published: June 2020

Soft electronics based on various rubbers have lately been needed in many advanced applications such as soft robotics, wearable electronics, and remote health monitoring. The ability of a self-sensing material to be monitored in use provides a significant advantage. However, conductive fillers usually used to increase conductivity also change mechanical properties. Most importantly, the initial sought-after properties of rubber, namely softness and long elastic deformation, are usually compromised. This work presents full mechanical and electro-mechanical characterization, together with self-sensing abilities of a vinyl methyl silicone rubber (VMQ) and multi-walled carbon nanotubes (MWCNTs) composite, featuring conductivity while maintaining low hardness. The research demonstrates that MWCNT/VMQ with just 4 wt.% of MWCNT are as conductive as commercial conductive VMQ based on Carbon Black, while exhibiting lower hardness and higher elastic recovery (~20% plastic deformation, similar to pure rubber). The research also demonstrates piezo-resistivity and Raman-sensitivity, allowing for self-sensing. Using morphological data, proposed mechanisms for the superior electrical and mechanical behavior, as well as the in-situ fingerprint for the composite conditions are presented. This research novelty is in the full MWCNT/VMQ mechanical and electro-mechanical characterization, thus demonstrating its ability to serve as a sensor over large local strains, multiple straining cycles, and environmental damage.
Design and Synthesis of Free-Radical/Cationic Photosensitive Resin Applied for 3D Printer with Liquid Crystal Display (LCD) Irradiation
Authors: Shan Junyang , Yang Zijun , Chen Guoguang , Hu Yang , Luo Ying , Dong Xianming , Zheng Wenxu , Zhou Wuyi
Published: June 2020

In this work, aiming at a UV-curing 3D printing process with liquid crystal display (LCD) irradiation, a novel free-radical/cationic hybrid photosensitive resin was designed and prepared. After testing, the results showed that the acrylate monomers could be polymerized through a free-radical mechanism, while the epoxides were polymerized by a cationic curing mechanism. During the process of UV-curing, the acrylate and epoxide polymers were crosslinked and further locked together by non-covalent bonds. Therefore, an interpenetrating polymer network (IPN) structure could be formed through light-curing 3D-printing processes. Fourier transform infrared spectroscopy (FT-IR) revealed that the 3,4-epoxy cyclohexyl methyl-3,4-epoxy cyclohexyl formate and acrylic resin were both successfully involved in the UV-curing process. Furthermore, in order to make the 3D-printed objects cured completely, post-processing was of great importance. The results from the systematic study of the dynamic mechanical properties of the printed objects showed that the heating treatment process after UV irradiation was very necessary and favorable for the complete cationic polymerization of UV-6110 induced by Irgacure 261. The optimum heating treatment conditions were achieved at a temperature of 70 °C for 3 h.
Preparation of Electrosprayed, Microporous Particle Filled Layers
Authors: Venkataraman Mohanapriya , Yang Kai , Xiong Xiaoman , Militky Jiri , Kremenakova Dana , Zhu Guocheng , Yao Juming , Wang Yan , Zhang Guoqing
Published: June 2020

Polytetrafluoroethylene (PTFE) is a synthetic fluoropolymer known for its excellent hydrophobic properties. In this work, samples from PTFE dispersions with different combinations of water and carbon microparticles were prepared using an electrospraying method. The morphologies and sizes of carbon particles were investigated and the properties of layers including roughness, hydrophobicity and electrical resistivity were investigated. The non-conductive carbon microparticles were selected as a model particle to check the compatibility and electrospraying ability, and it had no effect on the hydrophobic and electrical properties. Carbon microparticles in polymer solution increased the degree of ionization and was found to be beneficial for the shape control of materials. The results showed that PTFE dispersion with the composition of water and carbon microparticles produced fine sphere particles and the layer fabricated with increased roughness. It was also found that the electrical resistivity and hydrophobicity of all the layers comparatively increased. The fabricated microporous layers can be used in various applications like interlining layer in multilayer textile sandwiches.