bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis
Authors: Dai Yiqun , Sun Xiaolong , Li Bohan , Ma Hui , Wu Pingping , Zhang Yingping , Zhu Meilin , Li Hong-Mei , Qin Minjian , Wu Cheng-Zhu
Published: March 2021

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.
Mutual Support of Ligand- and Structure-Based Approaches—To What Extent We Can Optimize the Power of Predictive Model? Case Study of Opioid Receptors
Authors: Podlewska Sabina , Kurczab Rafał
Published: March 2021

The process of modern drug design would not exist in the current form without computational methods. They are part of every stage of the drug design pipeline, supporting the search and optimization of new bioactive substances. Nevertheless, despite the great help that is offered by in silico strategies, the power of computational methods strongly depends on the input data supplied at the stage of the predictive model construction. The studies on the efficiency of the computational protocols most often focus on global efficiency. They use general parameters that refer to the whole dataset, such as accuracy, precision, mean squared error, etc. In the study, we examined machine learning predictions obtained for opioid receptors (mu, kappa, delta) and focused on cases for which the predictions were the most accurate and the least accurate. Moreover, by using docking, we tried to explain prediction errors. We attempted to develop a rule of thumb, which can help in the prediction of compound activity towards opioid receptors via docking, especially those that have been incorrectly predicted by machine learning. We found out that although the combination of ligand- and structure-based path can be beneficial for the prediction accuracy, there still remain cases that cannot be reliably predicted by any available modeling method. In addition to challenging ligand- and structure-based predictions, we also examined the role of the application of machine-learning methods in comparison to simple statistical methods for both standard ligand-based representations (molecular fingerprints) and interaction fingerprints. All approaches were confronted in both classification (where compounds were assigned to the group of active and inactive group constructed on the basis of Ki values) and regression (where exact Ki value was predicted) experiments.
Synthesis, Antiproliferative Activity and Radical Scavenging Ability of 5-O-Acyl Derivatives of Quercetin
Authors: Lo Stephen , Leung Euphemia , Fedrizzi Bruno , Barker David
Published: March 2021

Quercetin is a flavonoid that is found in many plant materials, including commonly eaten fruits and vegetables. The compound is well known for its wide range of biological activities. In this study, 5-O-acyl derivatives of quercetin were synthesised and assessed for their antiproliferative activity against the HCT116 colon cancer and MDA-MB-231 breast cancer cell lines; and their radical scavenging activity against the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical species. Four derivatives were found to have improved the antiproliferative activity compared to quercetin whilst retaining radical scavenging activity.
7-(2-Anilinopyrimidin-4-yl)-1-benzazepin-2-ones Designed by a “Cut and Glue” Strategy Are Dual Aurora A/VEGF-R Kinase Inhibitors
Authors: Karatas Mehmet , Chaikuad Apirat , Berger Bianca , Kubbutat Michael H. G. , Totzke Frank , Knapp Stefan , Kunick Conrad
Published: March 2021

Although overexpression and hyperactivity of protein kinases are causative for a wide range of human cancers, protein kinase inhibitors currently approved as cancer drugs address only a limited number of these enzymes. To identify new chemotypes addressing alternative protein kinases, the basic structure of a known PLK1/VEGF-R2 inhibitor class was formally dissected and reassembled. The resulting 7-(2-anilinopyrimidin-4-yl)-1-benzazepin-2-ones were synthesized and proved to be dual inhibitors of Aurora A kinase and VEGF receptor kinases. Crystal structures of two representatives of the new chemotype in complex with Aurora A showed the ligand orientation in the ATP binding pocket and provided the basis for rational structural modifications. Congeners with attached sulfamide substituents retained Aurora A inhibitory activity. In vitro screening of two members of the new kinase inhibitor family against the cancer cell line panel of the National Cancer Institute (NCI) showed antiproliferative activity in the single-digit micromolar concentration range in the majority of the cell lines.
Phloridzin Acts as an Inhibitor of Protein-Tyrosine Phosphatase MEG2 Relevant to Insulin Resistance
Authors: Yoon Sun-Young , Yu Jae Sik , Hwang Ji Young , So Hae Min , Seo Seung Oh , Kim Jung Kyu , Jang Tae Su , Chung Sang J. , Kim Ki Hyun
Published: March 2021

Inhibition of the megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2, also named PTPN9) activity has been shown to be a potential therapeutic strategy for the treatment of type 2 diabetes. Previously, we reported that PTP-MEG2 knockdown enhances adenosine monophosphate activated protein kinase (AMPK) phosphorylation, suggesting that PTP-MEG2 may be a potential antidiabetic target. In this study, we found that phloridzin, isolated from Ulmus davidiana var. japonica, inhibits the catalytic activity of PTP-MEG2 (half-inhibitory concentration, IC50 = 32 ± 1.06 μM) in vitro, indicating that it could be a potential antidiabetic drug candidate. Importantly, phloridzin stimulated glucose uptake by differentiated 3T3-L1 adipocytes and C2C12 muscle cells compared to that by the control cells. Moreover, phloridzin led to the enhanced phosphorylation of AMPK and Akt relevant to increased insulin sensitivity. Importantly, phloridzin attenuated palmitate-induced insulin resistance in C2C12 muscle cells. We also found that phloridzin did not accelerate adipocyte differentiation, suggesting that phloridzin improves insulin sensitivity without significant lipid accumulation. Taken together, our results demonstrate that phloridzin, an inhibitor of PTP-MEG2, stimulates glucose uptake through the activation of both AMPK and Akt signaling pathways. These results strongly suggest that phloridzin could be used as a potential therapeutic candidate for the treatment of type 2 diabetes.
Rate Dependence on Inductive and Resonance Effects for the Organocatalyzed Enantioselective Conjugate Addition of Alkenyl and Alkynyl Boronic Acids to β-Indolyl Enones and β-Pyrrolyl Enones
Authors: Boylan Amy , Nguyen Thien S. , Lundy Brian J. , Li Jian-Yuan , Vallakati Ravikrishna , Sundstrom Sasha , May Jeremy A.
Published: March 2021

Two key factors bear on reaction rates for the conjugate addition of alkenyl boronic acids to heteroaryl-appended enones: the proximity of inductively electron-withdrawing heteroatoms to the site of bond formation and the resonance contribution of available heteroatom lone pairs to stabilize the developing positive charge at the enone β-position. For the former, the closer the heteroatom is to the enone β-carbon, the faster the reaction. For the latter, greater resonance stabilization of the benzylic cationic charge accelerates the reaction. Thus, reaction rates are increased by the closer proximity of inductive electron-withdrawing elements, but if resonance effects are involved, then increased rates are observed with electron-donating ability. Evidence for these trends in isomeric substrates is presented, and the application of these insights has allowed for reaction conditions that provide improved reactivity with previously problematic substrates.
Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study
Authors: di Leo Nicoletta , Moscato Stefania , Borso' Marco , Sestito Simona , Polini Beatrice , Bandini Lavinia , Grillone Agostina , Battaglini Matteo , Saba Alessandro , Mattii Letizia , Ciofani Gianni , Chiellini Grazia
Published: March 2021

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.
Predictive Capability of QSAR Models Based on the CompTox Zebrafish Embryo Assays: An Imbalanced Classification Problem
Authors: Lovrić Mario , Malev Olga , Klobučar Göran , Kern Roman , Liu Jay J. , Lučić Bono
Published: March 2021

The CompTox Chemistry Dashboard (ToxCast) contains one of the largest public databases on Zebrafish (Danio rerio) developmental toxicity. The data consists of 19 toxicological endpoints on unique 1018 compounds measured in relatively low concentration ranges. The endpoints are related to developmental effects occurring in dechorionated zebrafish embryos for 120 hours post fertilization and monitored via gross malformations and mortality. We report the predictive capability of 209 quantitative structure–activity relationship (QSAR) models developed by machine learning methods using penalization techniques and diverse model quality metrics to cope with the imbalanced endpoints. All these QSAR models were generated to test how the imbalanced classification (toxic or non-toxic) endpoints could be predicted regardless which of three algorithms is used: logistic regression, multi-layer perceptron, or random forests. Additionally, QSAR toxicity models are developed starting from sets of classical molecular descriptors, structural fingerprints and their combinations. Only 8 out of 209 models passed the 0.20 Matthew’s correlation coefficient value defined a priori as a threshold for acceptable model quality on the test sets. The best models were obtained for endpoints mortality (MORT), ActivityScore and JAW (deformation). The low predictability of the QSAR model developed from the zebrafish embryotoxicity data in the database is mainly due to a higher sensitivity of 19 measurements of endpoints carried out on dechorionated embryos at low concentrations.
A Review of Red Yeast Rice, a Traditional Fermented Food in Japan and East Asia: Its Characteristic Ingredients and Application in the Maintenance and Improvement of Health in Lipid Metabolism and the Circulatory System
Authors: Fukami Hiroyuki , Higa Yuki , Hisano Tomohiro , Asano Koichi , Hirata Tetsuya , Nishibe Sansei
Published: March 2021

Red yeast rice has been used to produce alcoholic beverages and various fermented foods in China and Korea since ancient times; it has also been used to produce tofuyo (Okinawan-style fermented tofu) in Japan since the 18th century. Recently, monacolin K (lovastatin) which has cholesterol-lowering effects, was found in some strains of Monascus fungi. Since statins have been used world-wide as a cholesterol-lowering agent, processed foods containing natural statins are drawing attention as materials for primary prevention of life-style related diseases. In recent years, large-scale commercial production of red yeast rice using traditional solid-state fermentation has become possible, and various useful materials, including a variety of monascus pigments (polyketides) that spread as natural pigments, in addition to statins, are produced in the fermentation process. Red yeast rice has a lot of potential as a medicinal food. In this paper, we describe the history of red yeast rice as food, especially in Japan and East Asia, its production methods, use, and the ingredients with pharmacological activity. We then review evidence of the beneficial effects of red yeast rice in improving lipid metabolism and the circulatory system and its safety as a functional food.
Antioxidant Activity Evaluation of Oviductus Ranae Protein Hydrolyzed by Different Proteases
Authors: Wang Shihan , Gan Yuanshuai , Mao Xinxin , Kan Hong , Li Nan , Zhang Changli , Wang Zhihan , Wang Yongsheng
Published: March 2021

As nutrition and a health tonic for both medicine and food, the protein content of Oviductus Ranae is more than 40%, making it an ideal source to produce antioxidant peptides. This work evaluated the effects of six different proteases (pepsin, trypsin, papain, flavourzyme, neutral protease and alcalase) on the antioxidant activity of Oviductus Ranae protein, and analyzed the relationship between the hydrolysis time, the degree of hydrolysis (DH) and the antioxidant activity of the enzymatic hydrolysates. The results showed that the antioxidant activity of Oviductus Ranae protein was significantly improved and the optimal hydrolysis time was maintained between 3–4 h under the action of different proteases. Among them, the protein hydrolysate which was hydrolyzed by pepsin for 180 min had the strongest comprehensive antioxidant activity and was most suitable for the production of antioxidant peptides. At this time, the DH, the DPPH radical scavenging activity, the absorbance value of reducing power determination and the hydroxyl radical scavenging activity corresponding to the enzymatic hydrolysate were 13.32 ± 0.24%, 70.63 ± 1.53%, 0.376 ± 0.009 and 31.96 ± 0.78%, respectively. Correlation analysis showed that there was a significant positive correlation between the hydrolysis time, the DH and the antioxidant activity of the enzymatic hydrolysates, further indicating that the hydrolysates of Oviductus Ranae protein had great antioxidant potential. The traditional anti-aging efficacy of Oviductus Ranae is closely related to the scavenging of reactive oxygen species, and its hydrolysates have better antioxidant capacity, which also provides support for further development of its traditional anti-aging efficacy.
Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals
Authors: Eckert Ralph W. , Wiemann Sabrina , Keck Cornelia M.
Published: March 2021

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.
Surface Tension of Liquid Organic Acids: An Artificial Neural Network Model
Authors: Pierantozzi Mariano , Mulero Ángel , Cachadiña Isidro
Published: March 2021

An artificial neural network model is proposed for the surface tension of liquid organic fatty acids covering a wide temperature range. A set of 2051 data collected for 98 acids (including carboxylic, aliphatic, and polyfunctional) was considered for the training, testing, and prediction of the resulting network model. Different architectures were explored, with the final choice giving the best results, in which the input layer has the reduced temperature (temperature divided by the critical point temperature), boiling temperature, and acentric factor as an independent variable, a 41-neuron hidden layer, and an output layer consisting of one neuron. The overall absolute percentage deviation is 1.33%, and the maximum percentage deviation is 14.53%. These results constitute a major improvement over the accuracy obtained using corresponding-states correlations from the literature.
Semi-Synthesis of Small Molecules of Aminocarbazoles: Tumor Growth Inhibition and Potential Impact on p53
Authors: Long Solida , Loureiro Joana B. , Carvalho Carla , Gales Luís , Saraiva Lucília , Pinto Madalena M. M. , Puthongking Ploenthip , Sousa Emília
Published: March 2021

The tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1), 7-methoxy heptaphylline (2), and 7-methoxymukonal (3), isolated from Clausena harmandiana, using a reductive amination protocol. Naturally-occurring carbazoles 1–3 and their amino derivatives were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole 1d showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound 1d. The results obtained indicate that carbazole alkaloids may represent a promising starting point to search for new mutp53-reactivating agents with promising applications in cancer therapy.
Short-Pulse Lasers: A Versatile Tool in Creating Novel Nano-/Micro-Structures and Compositional Analysis for Healthcare and Wellbeing Challenges
Authors: Al-Kattan Ahmed , Grojo David , Drouet Christophe , Mouskeftaras Alexandros , Delaporte Philippe , Casanova Adrien , Robin Jérôme D. , Magdinier Frédérique , Alloncle Patricia , Constantinescu Catalin , Motto-Ros Vincent , Hermann Jörg
Published: March 2021

Driven by flexibility, precision, repeatability and eco-friendliness, laser-based technologies have attracted great interest to engineer or to analyze materials in various fields including energy, environment, biology and medicine. A major advantage of laser processing relies on the ability to directly structure matter at different scales and to prepare novel materials with unique physical and chemical properties. It is also a contact-free approach that makes it possible to work in inert or reactive liquid or gaseous environment. This leads today to a unique opportunity for designing, fabricating and even analyzing novel complex bio-systems. To illustrate this potential, in this paper, we gather our recent research on four types of laser-based methods relevant for nano-/micro-scale applications. First, we present and discuss pulsed laser ablation in liquid, exploited today for synthetizing ultraclean “bare” nanoparticles attractive for medicine and tissue engineering applications. Second, we discuss robust methods for rapid surface and bulk machining (subtractive manufacturing) at different scales by laser ablation. Among them, the microsphere-assisted laser surface engineering is detailed for its appropriateness to design structured substrates with hierarchically periodic patterns at nano-/micro-scale without chemical treatments. Third, we address the laser-induced forward transfer, a technology based on direct laser printing, to transfer and assemble a multitude of materials (additive structuring), including biological moiety without alteration of functionality. Finally, the fourth method is about chemical analysis: we present the potential of laser-induced breakdown spectroscopy, providing a unique tool for contact-free and space-resolved elemental analysis of organic materials. Overall, we present and discuss the prospect and complementarity of emerging reliable laser technologies, to address challenges in materials’ preparation relevant for the development of innovative multi-scale and multi-material platforms for bio-applications.
Wound Healing Composite Materials of Bacterial Cellulose and Zinc Oxide Nanoparticles with Immobilized Betulin Diphosphate
Authors: Melnikova Nina , Knyazev Alexander , Nikolskiy Viktor , Peretyagin Peter , Belyaeva Kseniia , Nazarova Natalia , Liyaskina Elena , Malygina Darina , Revin Viktor
Published: March 2021

A design of new nanocomposites of bacterial cellulose (BC) and betulin diphosphate (BDP) pre-impregnated into the surface of zinc oxide nanoparticles (ZnO NPs) for the production of wound dressings is proposed. The sizes of crystalline BC and ZnO NPs (5–25%) corresponded to 5–6 nm and 10–18 nm, respectively (powder X-ray diffractometry (PXRD), Fourier-infrared (FTIR), ultraviolet (UV), atomic absorption (AAS) and photoluminescence (PL) spectroscopies). The biological activity of the wound dressings “BC-ZnO NPs-BDP” was investigated in rats using a burn wound model. Morpho-histological studies have shown that more intensive healing was observed during treatment with hydrophilic nanocomposites than the oleophilic standard (ZnO NPs-BDP oleogel; p < 0.001). Treatment by both hydrophilic and lipophilic agents led to increases in antioxidant enzyme activity (superoxide dismutase (SOD), catalase) in erythrocytes and decreases in the malondialdehyde (MDA) concentration by 7, 10 and 21 days (p < 0.001). The microcirculation index was restored on the 3rd day after burn under treatment with BC-ZnO NPs-BDP wound dressings. The results of effective wound healing with BC-ZnO NPs-BDP nanocomposites can be explained by the synergistic effect of all nanocomposite components, which regulate oxygenation and microcirculation, reducing hypoxia and oxidative stress in a burn wound.
On Tailoring Co-Precipitation Synthesis to Maximize Production Yield of Nanocrystalline Wurtzite ZnS
Authors: Krsmanović Whiffen Radenka , Montone Amelia , Pietrelli Loris , Pilloni Luciano
Published: March 2021

Pyroelectric materials can harvest energy from naturally occurring ambient temperature changes, as well as from artificial temperature changes, notably from industrial activity. Wurtzite- based materials have the advantage of being cheap, non-toxic, and offering excellent opto-electrical properties. Due to their non-centrosymmetric nature, all wurtzite crystals have both piezoelectric and pyroelectric properties. Nanocrystalline wurtzite ZnS, being a room temperature stable material, by contrast to its bulk counterpart, is interesting due to its still not well-explored potential in piezoelectric and pyroelectric energy harvesting. An easy synthesis method—a co-precipitation technique—was selected and successfully tailored for nanocrystalline wurtzite ZnS production. ZnS nanopowder with nanoparticles of 3 to 5 nm in size was synthesized in ethyl glycol under medium temperature conditions using ZnCl2 and thiourea as the sources of Zn and S, respectively. The purified and dried ZnS nanopowder was characterized by conventional methods (XRD, SEM, TEM, TG and FTIR). Finally, a constructed in-house pilot plant that is able to produce substantial amounts of wurtzite ZnS nanopowder in an environmentally friendly and cost-effective way is introduced and described.
Strengthening Mechanisms in CoCrFeNiX0.4 (Al, Nb, Ta) High Entropy Alloys Fabricated by Powder Plasma Arc Additive Manufacturing
Authors: Zhang Yupeng , Shen Qingkai , Chen Xizhang , Jayalakshmi Subramanian , Singh Ramachandra Arvind , Konovalov Sergey , Deev Vladislav B. , Prusov Evgeny S.
Published: March 2021

In high entropy alloys (HEAs), the addition of large-size atoms results in lattice distortion and further leads to solid solution strengthening or precipitation strengthening. However, the relationship between atomic radius, solid solution strengthening and precipitation strengthening has not been discerned yet. In this work, CoCrFeNiX0.4 (X = Al, Nb, Ta, with an equi-atomic radius) HEAs were prepared by powder plasma arc additive manufacturing (PPA-AM) and evaluated for their mechanical properties. Compression and nano-indentation hardness tests showed that the HEA with Ta showed the best properties. The influence of atomic radius and solid solubility on solid solution strengthening was investigated and the main strengthening mechanism that determines the mechanical properties of the developed HEAs was analyzed. The results showed that (i) the CoCrFeNiAl0.4 alloy did not show any solid solution strengthening effect and that a clear relation between solid solution strengthening and atomic size was not observed; (ii) in both CoCrFeNiTa0.4 and CoCrFeNiNb0.4 HEAs, precipitation strengthening and grain boundary strengthening effects are observed, wherein the difference in mechanical properties between both the alloys can be mainly attributed to the formation of fine eutectic structure in CoCrFeNiTa0.4; and (iii) from the microstructural analyses, it was identified that, in the CoCrFeNiTa0.4 HEA, the location containing a fine eutectic structure is accompanied by the formation of low-angle grain boundaries (LAGBs), which is also the region where deformed grains gather, giving rise to improved mechanical strengthening.
Polyurethane Foams Loaded with Carbon Nanofibers for Oil Spill Recovery: Mechanical Properties under Fatigue Conditions and Selective Absorption in Oil/Water Mixtures
Authors: Visco Annamaria , Quattrocchi Antonino , Nocita Davide , Montanini Roberto , Pistone Alessandro
Published: March 2021

Marine pollution due to spillage of hydrocarbons represents a well-known current environmental problem. In order to recover the otherwise wasted oils and to prevent pollution damage, polyurethane foams are considered suitable materials for their ability to separate oils from sea-water and for their reusability. In this work we studied polyurethane foams filled with carbon nanofibers, in varying amounts, aimed at enhancing the selectivity of the material towards the oils and at improving the mechanical durability of the foam. Polyurethane-based foams were experimentally characterized by morphological, surface, and mechanical analyses (optical microscopy observation, contact angle measurement, absorption test according to ASTM F726-99 standard and compression fatigue tests according to ISO 24999 standard). Results indicated an increase in hydrophobic behavior and a good oleophilic character of the composite sponges besides an improved selective absorption of the foam toward oils in mixed water/oil media. The optimal filler amount was found to be around 1 wt% for the homogeneous distribution inside the polymeric foam. Finally, the fatigue test results showed an improvement of the mechanical properties of the foam with the growing carbon filler amount.
Interfacial Strengthening of Graphene/Aluminum Composites through Point Defects: A First-Principles Study
Authors: Zhang Xin , Wang Shaoqing
Published: March 2021

The relationship between point defects and mechanical properties has not been fully understood yet from a theoretical perspective. This study systematically investigated how the Stone–Wales (SW) defect, the single vacancy (SV), and the double vacancy (DV) affect the mechanical properties of graphene/aluminum composites. The interfacial bonding energies containing the SW and DV defects were about twice that of the pristine graphene. Surprisingly, the interfacial bonding energy of the composites with single vacancy was almost four times that of without defect in graphene. These results indicate that point defects enhance the interfacial bonding strength significantly and thus improve the mechanical properties of graphene/aluminum composites, especially the SV defect. The differential charge density elucidates that the formation of strong Al–C covalent bonds at the defects is the most fundamental reason for improving the mechanical properties of graphene/aluminum composites. The theoretical research results show the defective graphene as the reinforcing phase is more promising to be used in the metal matrix composites, which will provide a novel design guideline for graphene reinforced metal matrix composites. Furthermore, the sp3-hybridized C dangling bonds increase the chemical activity of the SV graphene, making it possible for the SV graphene/aluminum composites to be used in the catalysis field.
Diet in the Treatment of Epilepsy
Authors: Westmark Cara J.
Published: March 2021

This Special Issue for Nutrients focuses on the effects of diet on brain function with a special emphasis on epileptic disorders [...]
The Role of Inflammatory Diet and Vitamin D on the Link between Periodontitis and Cognitive Function: A Mediation Analysis in Older Adults
Authors: Botelho João , Leira Yago , Viana João , Machado Vanessa , Lyra Patrícia , Aldrey José Manuel , Pías-Peleteiro Juan Manuel , Blanco Juan , Sobrino Tomás , Mendes José João
Published: March 2021

Patients suffering from periodontitis are at a higher risk of developing cognitive dysfunction. However, the mediation effect of an inflammatory diet and serum vitamin D levels in this link is unclear. In total, 2062 participants aged 60 years or older with complete periodontal diagnosis and cognitive tests from the National Health and Nutrition Examination Survey (NHANES) 2011–2012 and 2013–2014 were enrolled. The Consortium to Establish a Registry for Alzheimer’s disease (CERAD) word learning subtest (WLT) and CERAD delayed recall test (DRT), the animal fluency test (AFT) and the digit symbol substitution test (DSST) was used. Dietary inflammatory index (DII) was computed via nutrition datasets. Mediation analysis tested the effects of DII and vitamin D levels in the association of mean probing depth (PD) and attachment loss (AL) in all four cognitive tests. Periodontitis patients obtained worse cognitive test scores than periodontally healthy individuals. DII was negatively associated with CERAD-WLT, CERAD-DRT, AFT and DSST, and was estimated to mediate between 9.2% and 36.4% of the total association between periodontitis with cognitive dysfunction (p < 0.05). Vitamin D showed a weak association between CERAD-DRT, AFT and DSST and was estimated to between 8.1% and 73.2% of the association between periodontitis and cognitive dysfunction (p < 0.05). The association between periodontitis and impaired cognitive function seems to be mediated both by a proinflammatory dietary load and vitamin D deficiency. Future studies should further explore these mediators in the periodontitis-cognitive decline link.
Vitamin A5/X, a New Food to Lipid Hormone Concept for a Nutritional Ligand to Control RXR-Mediated Signaling
Authors: Krężel Wojciech , Rivas Aurea , Szklenar Monika , Ciancia Marion , Alvarez Rosana , de Lera Angel R. , Rühl Ralph
Published: March 2021

Vitamin A is a family of derivatives synthesized from carotenoids acquired from the diet and can be converted in animals to bioactive forms essential for life. Vitamin A1 (all-trans-retinol/ATROL) and provitamin A1 (all-trans-β,β-carotene/ATBC) are precursors of all-trans-retinoic acid acting as a ligand for the retinoic acid receptors. The contribution of ATROL and ATBC to formation of 9-cis-13,14-dihydroretinoic acid (9CDHRA), the only endogenous retinoid acting as retinoid X receptor (RXR) ligand, remains unknown. To address this point novel and already known retinoids and carotenoids were stereoselectively synthesized and administered in vitro to oligodendrocyte cell culture and supplemented in vivo (orally) to mice with a following high-performance liquid chromatography-mass spectrometry (HPLC-MS)/UV-Vis based metabolic profiling. In this study, we show that ATROL and ATBC are at best only weak and non-selective precursors of 9CDHRA. Instead, we identify 9-cis-13,14-dihydroretinol (9CDHROL) and 9-cis-13,14-dihydro-β,β-carotene (9CDHBC) as novel direct nutritional precursors of 9CDHRA, which are present endogenously in humans and the human food chain matrix. Furthermore, 9CDHROL displayed RXR-dependent promnemonic activity in working memory test similar to that reported for 9CDHRA. We also propose that the endogenous carotenoid 9-cis-β,β-carotene (9CBC) can act as weak, indirect precursor of 9CDHRA via hydrogenation to 9CDHBC and further metabolism to 9CDHROL and/or 9CDHRA. In summary, since classical vitamin A1 is not an efficient 9CDHRA precursor, we conclude that this group of molecules constitutes a new class of vitamin or a new independent member of the vitamin A family, named “Vitamin A5/X”.
Prevention and Management with Pro-, Pre and Synbiotics in Children with Asthma and Allergic Rhinitis: A Narrative Review
Authors: Meirlaen Lien , Levy Elvira Ingrid , Vandenplas Yvan
Published: March 2021

Allergic diseases including allergic rhinitis and asthma are increasing in the developing world, related to a westernizing lifestyle, while the prevalence is stable and decreasing in the industrialized world. This paper aims to answer the question if prevention and/or treatment of allergic rhinitis and asthma can be achieved by administrating pro-, pre- and/or synbiotics that might contribute to stabilizing the disturbed microbiome that influences the immune system through the gut–lung axis. We searched for relevant English articles in PubMed and Google Scholar. Articles interesting for the topic were selected using subject heading and key words. Interesting references in included articles were also considered. While there is substantial evidence from animal studies in well controlled conditions that selected probiotic strains may offer benefits in the prevention of wheezing and asthma, outcomes from clinical studies in infants (including as well pre- and postnatal administration) are disappointing. The latter may be related to the multiple confounding factors such as environment, strain selection and dosage, moment of administration and genetic background. There is little evidence to recommend administration of pro, pre- or synbiotics in the prevention of asthma and allergic rhinitis in children.
Impact of 2′-Fucosyllactose on Gut Microbiota Composition in Adults with Chronic Gastrointestinal Conditions: Batch Culture Fermentation Model and Pilot Clinical Trial Findings
Authors: Ryan Jennifer Joan , Monteagudo-Mera Andrea , Contractor Nikhat , Gibson Glenn R.
Published: March 2021

Intestinal dysbiosis has been described in patients with certain gastrointestinal conditions including irritable bowel syndrome (IBS) and ulcerative colitis. 2′-fucosyllactose (2′-FL), a prebiotic human milk oligosaccharide, is considered bifidogenic and butyrogenic. To assess prebiotic effects of 2′-FL, alone or in combination with probiotic strains (potential synbiotics), in vitro experiments were conducted on stool from healthy, IBS, and ulcerative colitis adult donors. In anaerobic batch culture fermenters, Bifidobacterium and Eubacterium rectale-Clostridium coccoides counts, and short-chain fatty acids (SCFAs) including butyrate increased during fermentation with 2′-FL and some of the 2′-FL/probiotic combinations. In a subsequent open-label pilot trial, the effect of a 2′-FL-containing nutritional formula was evaluated in twelve adults with IBS or ulcerative colitis. Gastrointestinal Quality of Life Index (GIQLI) total and gastrointestinal symptoms domain scores, stool counts of Bifidobacterium and Faecalibacterium prausnitzii, and stool SCFAs including butyrate, increased after six weeks of intervention. Consistent with documented effects of 2′-FL, the batch culture fermentation experiments demonstrated bifidogenic and butyrogenic effects of 2′-FL during fermentation with human stool samples. Consumption of the 2′-FL-containing nutritional formula by adults with IBS or ulcerative colitis was associated with improvements in intra- and extra-intestinal symptoms, and bifidogenic and butyrogenic effects.
Current Management of Hyperkalemia in Non-Dialysis CKD: Longitudinal Study of Patients Receiving Stable Nephrology Care
Authors: Borrelli Silvio , De Nicola Luca , Minutolo Roberto , Conte Giuseppe , Chiodini Paolo , Cupisti Adamasco , Santoro Domenico , Calabrese Vincenzo , Giannese Domenico , Garofalo Carlo , Provenzano Michele , Bellizzi Vincenzo , Apicella Luca , Piccoli Giorgina Barbara , Torreggiani Massimo , Di Iorio Biagio Raffaele
Published: March 2021

Background: No study has explored the limitations of current long-term management of hyperkalemia (HK) in outpatient CKD clinics. Methods: We evaluated the association between current therapeutic options and control of serum K (sK) during 12-month follow up in ND-CKD patients stratified in four groups by HK (sK ≥ 5.0 mEq/L) at baseline and month 12: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). Results: We studied 562 patients (age 66.2 ± 14.5 y; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m2, RAASI 76.2%). HK was “absent” in 50.7%, “resolving” in 15.6%, “new onset” in 16.6%, and “persistent” in 17.1%. Twenty-four hour urinary measurements testified adherence to nutritional recommendations in the four groups at either visit. We detected increased prescription from baseline to month 12 of bicarbonate supplements (from 5.0 to 14.1%, p < 0.0001), K-binders (from 2.0 to 7.7%, p < 0.0001), and non-K sparing diuretics (from 34.3 to 41.5%, p < 0.001); these changes were consistent across groups. Similar results were obtained when using higher sK level (≥5.5 mEq/L) to stratify patients. Mixed-effects regression analysis showed that higher sK over time was associated with eGFR < 60, diabetes, lower serum bicarbonate, lower use of non-K sparing diuretics, bicarbonate supplementation, and K-binder use. Treatment-by-time interaction showed that sK decreased in HK patients given bicarbonate (p = 0.003) and K-binders (p = 0.005). Conclusions: This observational study discloses that one-third of ND-CKD patients under nephrology care remain with or develop HK during a 12-month period despite low K intake and increased use of sK-lowering drugs.
A Food Insecurity Systematic Review: Experience from Malaysia
Authors: Sulaiman Norhasmah , Yeatman Heather , Russell Joanna , Law Leh Shii
Published: March 2021

Living free from hunger is a basic human right. However, some communities still experience household food insecurity. This systematic literature review explored different aspects of household food insecurity in Malaysia including vulnerable groups, prevalence, risk factors, coping strategies, and the consequences of food insecurity. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Thirty-three relevant articles were selected from scientific databases such as CINAHL, Pubmed and Google Scholar, scrutiny of reference lists, and personal communication with experts in the field. The prevalence of household food insecurity in Malaysia was unexpectedly reported as high, with affected groups including Orang Asli, low-income household/welfare-recipient households, university students, and the elderly. Demographic risk factors and socioeconomic characteristics included larger household, living in poverty, and low education. Coping strategies were practices to increase the accessibility of food in their households. Consequences of household food insecurity included psychological, dietary (macro- and micronutrient intakes), nutritional status, and health impacts. In conclusion, this review confirmed that household food insecurity in Malaysia continues to exist. Nevertheless, extensive and active investigations are encouraged to obtain a more holistic and comprehensive picture pertaining to household food security in Malaysia.
Wait-and-See Approach or Gluten-Free Diet Administration—The Rational Management of Potential Coeliac Disease
Authors: Szaflarska-Popławska Anna
Published: March 2021

Potential celiac disease (PCD) is a heterogeneous disease; only some patients develop full celiac disease (CD), characterised by advanced atrophic changes in the small intestine. Few accurate prognostic factors exist for the progression of PCD; therefore, therapeutic decisions should be made on an individual basis in each case. Patients with clinical gastroenterological or parenteral symptoms often benefit from a gluten-free diet, and those left on a diet containing gluten should receive clinical, serological and histopathological supervision.
Whole-Genome Sequencing and Comparative Genomics of Three Helicobacter pylori Strains Isolated from the Stomach of a Patient with Adenocarcinoma
Authors: Palau Montserrat , Piqué Núria , Ramírez-Lázaro M. José , Lario Sergio , Calvet Xavier , Miñana-Galbis David
Published: March 2021

Helicobacter pylori is a common pathogen associated with several severe digestive diseases. Although multiple virulence factors have been described, it is still unclear the role of virulence factors on H. pylori pathogenesis and disease progression. Whole genome sequencing could help to find genetic markers of virulence strains. In this work, we analyzed three complete genomes from isolates obtained at the same point in time from a stomach of a patient with adenocarcinoma, using multiple available bioinformatics tools. The genome analysis of the strains B508A-S1, B508A-T2A and B508A-T4 revealed that they were cagA, babA and sabB/hopO negative. The differences among the three genomes were mainly related to outer membrane proteins, methylases, restriction modification systems and flagellar biosynthesis proteins. The strain B508A-T2A was the only one presenting the genotype vacA s1, and had the most distinct genome as it exhibited fewer shared genes, higher number of unique genes, and more polymorphisms were found in this genome. With all the accumulated information, no significant differences were found among the isolates regarding virulence and origin of the isolates. Nevertheless, some B508A-T2A genome characteristics could be linked to the pathogenicity of H. pylori.
Malacoplakia of the Uterine Cervix: A Case Report
Authors: Saco Adela , Rakislova Natalia , Marimon Lorena , Torne Aureli , Diaz-Feijoo Berta , Salvador Rafael , Alos Silvia , Jordao Dercio , Hurtado Juan Carlos , Ordi Jaume
Published: March 2021

Malacoplakia is an uncommon chronic granulomatous inflammation that rarely affects the female genital tract. A case of a 78-year-old woman with malacoplakia involving the uterine cervix and the vagina is described. The patient complained of vaginal bleeding. Clinically, a 13-mm mass was detected in the cervix, which was confirmed by ultrasound scan and magnetic resonance imaging. Histological examination showed a dense histiocytic infiltrate with abundant Michaelis–Gutmann bodies involving the uterine cervix and the upper vagina. The presence of Escherichia coli was confirmed in the lesion by immunohistochemistry and polymerase chain reaction. Only 12 cases of cervical malacoplakia have been reported to date. This condition should be included in the differential diagnosis of cervical tumors.
3-Hydroxypropane-1,2-Diyl Dipalmitoleate—A Natural Compound with Dual Roles (CB1 Agonist/FAAH1 Blocker) in Inhibiting Ovarian Cancer Cell Line
Authors: Sathynathan Christina Vijayaraghavan , Raman Lakshmi Sundaram , Vajiravelu Sivamurugan , Kumar Thirumal D. , Panchatcharam Thyagarajan Sadras , Narasimhan Gopinathan , Doss George C. Priya , Krishnan Mary Elizabeth Gnanambal
Published: March 2021

Though it was once known that upregulated Cannabinoid Receptor (CB1) and downregulated Fatty Acid Amide Hydrolase (FAAH1) are associated with tumour aggressiveness and metastasis, it is now clear that upregulated CB1 levels more than a certain point cause accumulation of ceramide and directs cells to apoptosis. Hence, CB1 analogues/FAAH1 blockers are explored widely as anticancer drugs. There are reports on CB1-agonists and FAAH1-blockers separately, however, dual activities along with ovarian cancer-specific links are not established for any natural compound. With this setting, we describe for the first time the isolation of 3-hydroxypropane-1,2-diyl dipalmitoleate (564.48 Da) from a marine snail, Conus inscriptus, which binds to both CB1 and FAAH1 (glide energies: −70.61 and −30.52 kcal/mol, respectively). MD simulations indicate stable compound–target interaction for a minimum of 50 nanoseconds with relative invariabilities in Rg. The compound inhibited ovarian cancer cell line, PA1 at 1.7 μM. Structural and chemical interpretation of the compound (C2) was done using FT-IR, GC-MS, ESI-MS, 1H and 13C-NMR (1 and 2D). Furthermore, a probable route for gram-scale synthesis of C2 is hinted herein. With the available preliminary data, molecular mechanisms involving dual roles for this potent molecule must be elucidated to understand the possibilities of usage as an anticancer drug.