bluuebunny/crossref_metadata_2025 huggingface dataset:
Andrographis paniculata (Burm. f.) Wall. ex Nees: An Updated Review of Phytochemistry, Antimicrobial Pharmacology, and Clinical Safety and Efficacy
Authors: Hossain Sanower , Urbi Zannat , Karuniawati Hidayah , Mohiuddin Ramisa Binti , Moh Qrimida Ahmed , Allzrag Akrm Mohamed Masaud , Ming Long Chiau , Pagano Ester , Capasso Raffaele
Published: April 2021

Infectious disease (ID) is one of the top-most serious threats to human health globally, further aggravated by antimicrobial resistance and lack of novel immunization options. Andrographis paniculata (Burm. f.) Wall. ex Nees and its metabolites have been long used to treat IDs. Andrographolide, derived from A. paniculata, can inhibit invasive microbes virulence factors and regulate the host immunity. Controlled clinical trials revealed that A. paniculata treatment is safe and efficacious for acute respiratory tract infections like common cold and sinusitis. Hence, A. paniculata, mainly andrographolide, could be considered as an excellent candidate for antimicrobial drug development. Considering the importance, medicinal values, and significant role as antimicrobial agents, this study critically evaluated the antimicrobial therapeutic potency of A. paniculata and its metabolites, focusing on the mechanism of action in inhibiting invasive microbes and biofilm formation. A critical evaluation of the secondary metabolites with the aim of identifying pure compounds that possess antimicrobial functions has further added significant values to this study. Notwithstanding that A. paniculata is a promising source of antimicrobial agents and safe treatment for IDs, further empirical research is warranted.
Definition of Sarcopenia in Chronic Liver Disease
Authors: Son Seong Wan , Song Do Seon , Chang U Im , Yang Jin Mo
Published: April 2021

Sarcopenia, which is characterized by decline in muscle mass, muscle strength, and physical performance, is common in patients with chronic liver disease (CLD) and is associated with poor clinical outcomes. Several consensus definitions for community-dwelling elderly people have been proposed, and these recommend the use of various tools and tests to assess muscle properties and performance. These measurement tools have also been applied in patients with CLD and have been useful for predicting prognosis. However, sarcopenia and its diagnostic criteria specific to patients with CLD have not yet been clearly defined. In addition, fluid retention and body composition should be considered when sarcopenia is assessed in patients with CLD. This review aims to introduce definitions of sarcopenia and diagnostic tools used in patients with CLD.
7-Docosahexaenoyl-Quercetin
Authors: Mazzotta Sarah , Carullo Gabriele , Sciubba Fabio , Di Cocco Maria Enrica , Aiello Francesca
Published: April 2021

Fatty acids and polyphenols represent different classes of pharmacologically active molecules. Hybrid derivatives of these compounds are interesting therapeutic tools. They could be obtained using enzymatic approaches, which allow regioselective derivatizations. In this short note, the pancreatic porcine lipase was employed to mediate the regioselective synthesis of 7-docosahexaenoyl-quercetin was described. The C-7 regioisomer formation was confirmed by 1H-NMR experiment. Generally, in this approach the alcoholic OH- was preferred when present. Nevertheless, in this case, it was demonstrated that the hindrance of the acyl group is a variable to obtain a good regioselectivity in C-7 position, employing only one-step reaction.
Assessment of the Dimensional and Geometric Precision of Micro-Details Produced by Material Jetting
Authors: Silva Miguel R. , Pereira António M. , Sampaio Álvaro M. , Pontes António J.
Published: April 2021

Additive Manufacturing (AM) technology has been increasing its penetration not only for the production of prototypes and validation models, but also for final parts. This technology allows producing parts with almost no geometry restrictions, even on a micro-scale. However, the micro-Detail (mD) measurement of complex parts remains an open field of investigation. To be able to develop all the potential that this technology offers, it is necessary to quantify a process’s precision limitations, repeatability, and reproducibility. New design methodologies focus on optimization, designing microstructured parts with a complex material distribution. These methodologies are based on mathematical formulations, whose numerical models assume the model discretization through volumetric unitary elements (voxels) with explicit dimensions and geometries. The accuracy of these models in predicting the behavior of the pieces is influenced by the fidelity of the object’s physical reproduction. Despite that the Material Jetting (MJ) process makes it possible to produce complex parts, it is crucial to experimentally establish the minimum dimensional and geometric limits to produce parts with mDs. This work aims to support designers and engineers in selecting the most appropriate scale to produce parts discretized by hexahedral meshes (cubes). This study evaluated the dimensional and geometric precision of MJ equipment in the production of mDs (cubes) comparing the nominal design dimensions. A Sample Test (ST) with different sizes of mDs was modeled and produced. The dimensional and geometric precision of the mDs were quantified concerning the nominal value and the calculated deviations. From the tests performed, it was possible to conclude that: (i) more than 90% of all analyzed mDs exhibit three dimensions (xyz) higher than the nominal ones; (ii) for micro-details smaller than 423 μm, they show a distorted geometry, and below 212 μm, printing fails.
The Potential Use of a Thin Film Gold Electrode Modified with Laccases for the Electrochemical Detection of Pyrethroid Metabolite 3-Phenoxybenzaldehyde
Authors: Esquivel-Blanco Verónica Aglaeé , Quintanilla-Villanueva Gabriela Elizabeth , Villarreal-Chiu  Juan Francisco , Rodríguez-Delgado José Manuel , Rodríguez-Delgado Melissa Marlene
Published: April 2021

There is increasing interest in developing portable technologies to detect human health threats through hybrid materials that integrate specific bioreceptors. This work proposes an electrochemical approach for detecting 3-Phenoxybenzaldehyde (3-PBD), a biomarker for monitoring human exposure to pyrethroid pesticides. The biosensor uses laccase enzymes as an alternative recognition element by direct oxidation of 3-PBD catalysts by the enzyme onto thin-film gold electrodes. The thin-film gold electrode modified by the immobilized laccase was characterized by Fourier-transform infrared spectrometry and scanning electron microscopy. The detection method’s electrochemical parameters were established, obtaining a linear range of 5 t 50 μM, the limit of detection, and quantification of 0.061 and 2.02 μM, respectively. The proposed biosensor’s analytical performance meets the concentration of pyrethroids detected in natural environments, reflecting its potential as an alternative analytical tool for monitoring the pyrethroid insecticide’s presence.
Fracture Parameters and Cracking Propagation of Cold Recycled Mixture Considering Material Heterogeneity Based on Extended Finite Element Method
Authors: Gao Lei , Deng Xingkuan , Zhang Ye , Ji Xue , Li Qiang
Published: April 2021

Cold recycled mixture (CRM) has been widely used around the world mainly because of its good ability to resist reflection cracking. In this study, mixed-mode cracking tests were carried out by the designed rotary test device to evaluate the cracking resistance of CRM. Through the finite element method, the heterogeneous model of CRM based on its meso-structure was established. The cracking process of CRM was simulated using the extended finite element method, and the influence of different notch lengths on its anti-cracking performance was studied. The results show that the mixed-mode fracture test method can effectively evaluate the cracking resistance of CRM by the proposed fracture parameters. The virtual tests under three of five kinds of mixed-cracking modes have good simulation to capture the cracking behavior of CRM. The effect of notch length on the initial crack angle and the crack propagation process of the CRM is mainly related to the distribution characteristics of its meso-structure. With the increase of the proportion of Mode II cracking, the crack development path gradually deviates, and the failure elements gradually increase. At any mixed-mode level, there is an obvious linear relationship between the peak load, fracture energy, and the notch length.
Bio-Based Plasticized PVA Based Polymer Blend Electrolytes for Energy Storage EDLC Devices: Ion Transport Parameters and Electrochemical Properties
Authors: Aziz Shujahadeen B. , Nofal Muaffaq M. , Kadir M. F. Z. , Dannoun Elham M. A. , Brza Mohamad A. , Hadi Jihad M. , Abdullah Ranjdar M.
Published: April 2021

This report shows a simple solution cast methodology to prepare plasticized polyvinyl alcohol (PVA)/methylcellulose (MC)-ammonium iodide (NH4I) electrolyte at room temperature. The maximum conducting membrane has a conductivity of 3.21 × 10−3 S/cm. It is shown that the number density, mobility and diffusion coefficient of ions are enhanced by increasing the glycerol. A number of electric and electrochemical properties of the electrolyte—impedance, dielectric properties, transference numbers, potential window, energy density, specific capacitance (Cs) and power density—were determined. From the determined electric and electrochemical properties, it is shown that PVA: MC-NH4I proton conducting polymer electrolyte (PE) is adequate for utilization in energy storage device (ESD). The decrease of charge transfer resistance with increasing plasticizer was observed from Bode plot. The analysis of dielectric properties has indicated that the plasticizer is a novel approach to increase the number of charge carriers. The electron and ion transference numbers were found. From the linear sweep voltammetry (LSV) response, the breakdown voltage of the electrolyte is determined. From Galvanostatic charge-discharge (GCD) measurement, the calculated Cs values are found to drop with increasing the number of cycles. The increment of internal resistance is shown by equivalent series resistance (ESR) plot. The energy and power density were studied over 250 cycles that results to the value of 5.38–3.59 Wh/kg and 757.58–347.22 W/kg, respectively.
All-Solid-State Lithium-Ion Batteries with Oxide/Sulfide Composite Electrolytes
Authors: Park Young Seon , Lee Jae Min , Yi Eun Jeong , Moon Ji-Woong , Hwang Haejin
Published: April 2021

Li6.3La3Zr1.65W0.35O12 (LLZO)-Li6PS5Cl (LPSC) composite electrolytes and all-solid-state cells containing LLZO-LPSC were fabricated by cold pressing at room temperature. The LPSC:LLZO ratio was varied, and the microstructure, ionic conductivity, and electrochemical performance of the corresponding composite electrolytes were investigated; the ionic conductivity of the composite electrolytes was three or four orders of magnitude higher than that of LLZO. The high conductivity of the composite electrolytes was attributed to the enhanced relative density and the rule of mixture for soft LPSC particles with high lithium-ion conductivity (~10−4 S·cm−1). The specific capacities of all-solid-state cells (ASSCs) consisting of a LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode and the composite electrolytes of LLZO:LPSC = 7:3 and 6:4 were 163 and 167 mAh·g−1, respectively, at 0.1 C and room temperature. Moreover, the charge–discharge curves of the ASSCs with the composite electrolytes revealed that a good interfacial contact was successfully formed between the NCM811 cathode and the LLZO-LPSC composite electrolyte.
Evaluation of the Effects of Filler Fineness on the Properties of an Epoxy Asphalt Mixture
Authors: Xu Wei , Wei Jintao , Chen Zhengxiong , Wang Feng , Zhao Jian
Published: April 2021

The type and fineness of a filler significantly affect the performance of an asphalt mixture. There is a lack of specific research on the effects of filler fineness and dust from aggregates on the properties of epoxy asphalt (EA) mixtures. The effects of aggregate dust and mineral powder on the properties of an EA mixture were evaluated. These filler were tested to determine their fineness, specific surface area and mineral composition. The effects of these fillers on the EA mastic sample and mixture were evaluated. The morphology of the EA mastic samples was analyzed using scanning electron microscopy (SEM). The effects of the fillers on the Marshall stability, tensile strength and fatigue performance of the EA mixture were evaluated. The dust from the aggregates exhibited an even particle size distribution, and its average particle size was approximately 20% of that of the mineral powder. The SEM microanalysis showed that the EA mastic sample containing relatively fine dust formed a tight and dense interfacial bonding structure with the aggregate. The EA mixture sample containing filler composed of dust from aggregate had a significantly higher strength and longer fatigue life than that of the EA sample containing filler composed of mineral powder.
Highly Hydrophobic Organosilane-Functionalized Cellulose: A Promising Filler for Thermoplastic Composites
Authors: Cerny Pavel , Bartos Petr , Kriz Pavel , Olsan Pavel , Spatenka Petr
Published: April 2021

The aim of this work is to design and optimize the process of functionalization of cellulose fibers by organosilane functional groups using low-pressure microwave plasma discharge with hexamethyldisiloxane (HMDSO) precursor in order to prepare a compatible hydrophobic filler for composites with nonpolar thermoplastic matrices. Particular attention was paid to the study of agglomeration of cellulose fibers in the mixture with polypropylene. In our contribution, the dependence of the surface wettability on used process gas and treatment time was investigated. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analyses were applied to characterize the surface morphology and chemical composition of the cellulose fibers. It was observed that the plasma treatment in oxygen process gas led to the functionalization of cellulose fibers by organosilane functional groups without degradation. In addition, the treated cellulose was highly hydrophobic with water contact angle up to 143°. The use of treated cellulose allowed to obtain a homogeneous mixture with polypropylene powder due to the significantly lower tendency of the functionalized cellulose fibers to agglomerate.
Structure and Properties of Co-Cr-Mo Alloy Manufactured by Powder Injection Molding Method
Authors: Matula Grzegorz , Szatkowska Aleksandra , Matus Krzysztof , Tomiczek Błażej , Pawlyta Mirosława
Published: April 2021

Cobalt–chromium–molybdenum alloys samples were obtained by the powder injection molding method (PIM). PIM is dedicated to the mass production of components and can manufacture several grades of dental screws, bolts, stabilizers, or implants. As a skeleton component, ethylene–vinyl acetate (EVA copolymer) with a low temperature of processing and softening point was used. The choice of a low-temperature binder made it necessary to use a coarse ceramic powder as a mechanical support of the green sample during sintering. The injection-molded materials were thermally degraded in N2 or Ar-5%H2 and further sintered in N2-5%H2 or Ar-5%H2 at 1300 or 1350 °C for 30 min. The structure of the obtained samples was characterized by X-ray diffraction and electron microscopy. Mechanical properties, including hardness and three-point bending tests, confirmed that a nitrogen-rich atmosphere significantly increases the bending strength compared to the material manufactured in Ar-5%H2. This is due to the precipitation of numerous fine nitrides and intermetallic phases that strengthen the ductile γ-phase matrix.
Vinyl-Functionalized Janus Ring Siloxane: Potential Precursors to Hybrid Functional Materials
Authors: Chaiprasert Thanawat , Liu Yujia , Takeda Nobuhiro , Unno Masafumi
Published: April 2021

A vinyl-functionalized all-cis-tetrasiloxycyclotetrasiloxane [ViSi(OSiMe2H)O]4 (Vi = vinyl group) Janus precursor was prepared from potassium cyclotetrasiloxane silanolate. The Janus precursor was selectively modified at its dimethylhydrosilyl groups [–SiMe2H] via the Piers–Rubinsztajn reaction to obtain a family of new tetravinyl-substituted Janus rings [ViSi(OR’)O]4 containing various functional groups in moderate yields. Remarkably, the tetravinyl groups on the structure remained intact after modification by the Piers–Rubinsztajn reaction. Since these synthesized compounds possess multiple functional groups (up to eight per molecule), they are potential precursors for advanced hybrid organic-inorganic functional materials.
Inhibition of SARS-CoV-2 Virus Entry by the Crude Polysaccharides of Seaweeds and Abalone Viscera In Vitro
Authors: Yim Sung-Kun , Kim Kian , Kim Inhee , Chun SangHo , Oh TaeHwan , Kim Jin-Ung , Kim Jungwon , Jung WooHuk , Moon Hosang , Ku Bosung , Jung Kyoojin
Published: April 2021

Much attention is being devoted to the potential of marine sulfated polysaccharides as antiviral agents in preventing COVID-19. In this study, sulfated fucoidan and crude polysaccharides, extracted from six seaweed species (Undaria pinnatifida sporophyll, Laminaria japonica, Hizikia fusiforme, Sargassum horneri, Codium fragile, Porphyra tenera) and Haliotis discus hannai (abalone viscera), were screened for their inhibitory activity against SARS-CoV-2 virus entry. Most of them showed significant antiviral activities at an IC50 of 12~289 μg/mL against SARS-CoV-2 pseudovirus in HEK293/ACE2, except for P. tenera (IC50 > 1000 μg/mL). The crude polysaccharide of S. horneri showed the strongest antiviral activity, with an IC50 of 12 μg/mL, to prevent COVID-19 entry, and abalone viscera and H. fusiforme could also inhibit SARS-CoV-2 infection with an IC50 of 33 μg/mL and 47 μg/mL, respectively. The common properties of these crude polysaccharides, which have strong antiviral activity, are high molecular weight (>800 kDa), high total carbohydrate (62.7~99.1%), high fucose content (37.3~66.2%), and highly branched polysaccharides. These results indicated that the crude polysaccharides from seaweeds and abalone viscera can effectively inhibit SARS-CoV-2 entry.
Anti-Food Allergic Compounds from Penicillium griseofulvum MCCC 3A00225, a Deep-Sea-Derived Fungus
Authors: Xing Cui-Ping , Chen Dan , Xie Chun-Lan , Liu Qingmei , Zhong Tian-Hua , Shao Zongze , Liu Guangming , Luo Lian-Zhong , Yang Xian-Wen
Published: April 2021

Ten new (1–10) and 26 known (11–36) compounds were isolated from Penicillium griseofulvum MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey’s method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound 13 significantly decreased the degranulation release with an IC50 value of 60.3 μM, compared to that of 91.6 μM of the positive control, loratadine.
Marine-Source Quorum Quenching Enzyme YtnP to Improve Hygiene Quality in Dental Units
Authors: Sun Xiaohui , Hill Philip , Liu Jia , Qian Jing , Ma Yuting , Zhou Shufeng
Published: April 2021

Biofilm in dental unit water lines may pose a health risk to patients and dental practitioners. An AdiC-like quorum quenching enzyme, YtnP, was cloned from a deep-sea probiotic Bacillus velezensis, and heterologously expressed in E. coli to examine the application on the improvement of hygiene problems caused by biofilm infection of Pseudomonas aeruginosa in dental units. Pseudomonas bacteria were isolated from dental chair units and used to grow static biofilms in the laboratory. A water filter system was designed to test the antifouling activity of YtnP in Laboratory, to simulate the biofilm contamination on water filter in dental unit water lines. The results demonstrated that the enzyme of YtnP was able to degrade the N-acyl homoserine lactones, significantly inhibited the EPS generation, biofilm formation, and virulence factors production (pyocyanin and rhamnolipid) of P. aeruginosa, and was efficient on the antifouling against P. aeruginosa. The findings in this study indicated the possibility of YtnP as novel disinfectant reagent for hygiene treatment in dental units.
Human-Centered Robotic Development in the Steel Shop: Improving Health, Safety and Digital Skills at the Workplace
Authors: Colla Valentina , Matino Ruben , Schröder Antonius Johannes , Schivalocchi Mauro , Romaniello Lea
Published: April 2021

Within the implementation of the Industry 4.0 paradigm in the steel sector, robots can play a relevant role in improving health and safety conditions at the workplace, by overtaking cumbersome, repetitive and risky operations. However, the implementation of robotics solutions in this particular sector is hampered by harsh operating conditions and by particular features of many procedures, which require a combination of force and sensitivity. Human–robot cooperation is a viable solution to overcome existing barriers, by synergistically combining human and robot abilities in the sense of a human-centered Industry 5.0. In this sense, robotics solution should be designed in a way to integrate and meet the end-users’ demands in a common development process for successfully implementation and widely acceptance. The paper presents the outcomes of the field evaluation of a robotic workstation, which was designed for a complex maintenance operation that is daily performed in the steel shop. The system derives from a co-creation process, where workers were involved since the beginning in the design process, according to the paradigm of social innovation combining technological and social development. Therefore, the evaluation aimed at assessing both system reliability and end-users’ satisfaction. The results show that the human-centered robotic workstations are successful in reducing cumbersome operations and improving workers’ health and safety conditions, and that this fact is clearly perceived by system users and developers.
An Overview of High-Entropy Alloys as Biomaterials
Authors: Castro Diogo , Jaeger Pedro , Baptista Ana Catarina , Oliveira João Pedro
Published: April 2021

High-entropy alloys (HEAs) have been around since 2004. The breakthroughs in this field led to several potential applications of these alloys as refractory, structural, functional, and biomedical materials. In this work, a short overview on the concept of high-entropy alloys is provided, as well as the theoretical design approach. The special focus of this review concerns one novel class of these alloys: biomedical high-entropy alloys. Here, a literature review on the potential high-entropy alloys for biomedical applications is presented. The characteristics that are required for these alloys to be used in biomedical-oriented applications, namely their mechanical and biocompatibility properties, are discussed and compared to commercially available Ti6Al4V. Different processing routes are also discussed.
Microfluidic Device for the Identification of Biological Sex by Analysis of Latent Fingermark Deposits
Authors: Marshall Jamila S. , Sita Madelyn L. , Landers James P.
Published: April 2021

To date, most research regarding amino acid detection and quantification in fingermarks relies on spectrometric methods. Herein, the Sakaguchi colorimetric test was adapted to a rotationally-driven microfluidic platform and used to detect and quantify arginine in fingermarks deposited by male and female donors. A red color indicates the presence of arginine in a given sample following the reaction, and the intensity of this color is linearly proportional to the concentration. Objective detection and quantification of arginine were accomplished using image analysis software (freeware) based on this colorimetric result. The mean concentrations obtained in a blind study were 96.4 ± 5.1 µM for samples from female donors and 55.3 ± 5.3 µM for samples from males. These were not statistically different from the literature values of 94.8 µM ± 12.9 µM for females (p = 0.908) and 54.0 ± 12.6 µM for males (p = 0.914), respectively (± SEM in all cases). Conversely, the experimental means from males and female samples were statistically different from each other (p < 0.001). Objective differentiation between male and female fingermark deposits was achieved in a blind study with 93% accuracy. Additionally, the method was compatible both with samples lifted from common surfaces and with magnetically-powdered samples.
Manganese Oxide Nanoparticles as Safer Seed Priming Agent to Improve Chlorophyll and Antioxidant Profiles in Watermelon Seedlings
Authors: Kasote Deepak M. , Lee Jisun H. J. , Jayaprakasha Guddarangavvanahally K. , Patil Bhimanagouda S.
Published: April 2021

The use of nanoscale nutrients in agriculture to improve crop productivity has grown in recent years. However, the bioefficacy, safety, and environmental toxicity of nanoparticles are not fully understood. Herein, we used onion bulb extract to synthesize manganese oxide nanoparticles (MnO-NPs). X-ray diffraction, X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy were used for the structural and morphological characterization of synthesized MnO-NPs. The MnO-NPs were oval shape crystalline nanoparticles of Mn2O3 with sizes 22–39 nm. In further studies, we assessed the comparative toxicity of seed priming with MnO-NPs and its bulk counterparts (KMnO4 and Mn2O3), which showed seed priming with MnO-NPs had comparatively less phytotoxicity. Investigating the effect of seed priming with different concentrations of MnO-NPs on the hormonal, phenolic acid, chlorophyll, and antioxidant profiles of watermelon seedlings showed that treatment with 20 mg·L−1 MnO-NPs altered the chlorophyll and antioxidant profiles of seedlings. At ≤40 mg·L−1, MnO-NPs had a remarkable effect on the phenolic acid and phytohormone profiles of the watermelon seedlings. The physiological outcomes of the MnO-NP seed priming in watermelon were genotype-specific and concentration-dependent. In conclusion, the MnO-NPs were safer than their bulk counterparts and could increase crop productivity.
Heated Corn Oil and 2,4-Decadienal Suppress Gastric Emptying and Energy Intake in Humans
Authors: Kashima Hideaki , Honma Ayumi , Kamimura Saori , Nishimura Saki , Sano Takashi , Matsumoto Shoji , Endo Masako , Fukuba Yoshiyuki
Published: April 2021

Consumption of 2,4-decadienal (2,4-DD) delays gastric emptying (GE) rate in animals. Oil heating produces 2,4-DD and other aldehydes. Here we examined whether heated oil affects GE rate and food intake in humans, and whether it is mediated by 2,4-DD. In the first experiment, 10 healthy volunteers consumed 240-g pumpkin soup with 9.2 g of heated (HO) or non-heated corn oil (CO). Subsequently, 17 participants consumed pumpkin soup containing 3.1 g of either heated corn oil (HO), 1 mg 2,4-DD + non-heated corn oil (2,4-DD), or non-heated corn oil (CO). Sixty minutes following pumpkin soup, cod roe spaghetti was provided, and then energy intake was determined. To evaluate GE rate, 13C breath test (Experiment 1) and ultrasonography (Experiments 1 and 2) were used. The results from the Experiment 1 confirmed that consumption of heated corn oil reduced GE rate. Experiment 2 showed a delayed GE rate in HO and 2,4-DD trials compared with CO trial (p < 0.05). Energy intake was approximately 600–650 kJ lower in HO and 2,4-DD trials compared with CO trial (p < 0.05). These findings suggest that 2,4-DD, either formed by oil heating or added to food, contributes to suppressing GE rate and energy intake.
Dietary Curdlan Enhances Bifidobacteria and Reduces Intestinal Inflammation in Mice
Authors: Rahman Shafaque , Davids Mark , van Hamersveld Patricia H. P. , Welting Olaf , Rahaoui Hakim , Schuren Frank , Meijer Sybren L. , van den Wijngaard René M. , Hakvoort Theodorus B. M. , de Jonge Wouter J. , Heinsbroek Sigrid E. M.
Published: April 2021

β-glucan consumption is known for its beneficial health effects, but the mode of action is unclear. While humans and mice lack the required enzymes to digest β-glucans, certain intestinal microbes can digest β-glucans, triggering gut microbial changes. Curdlan, a particulate β-glucan isolated from Alcaligenes faecalis, is used as a food additive. In this study we determined the effect of curdlan intake in mice on the intestinal microbiota and dextran sodium sulfate (DSS)-induced intestinal inflammation. The effect of curdlan on the human intestinal microbiota was assessed using i-screen, an assay for studying anaerobic microbial interactions. Mice received oral gavage with vehicle or curdlan for 14 days followed by DSS for 7 days. The curdlan-fed group showed reduced weight loss and colonic inflammation compared to the vehicle-fed group. Curdlan intake did not induce general microbiota community changes, although a specific Bifidobacterium, closely related to Bifidobacterium choerinum, was observed to be 10- to 100-fold more prevalent in the curdlan-fed group under control and colitis conditions, respectively. When tested in i-screen, curdlan induced a global change in the microbial composition of the healthy intestinal microbiota from a human. Overall, these results suggest that dietary curdlan induces microbiota changes that could reduce intestinal inflammation.
The Immunomodulatory Properties of β-2,6 Fructans: A Comprehensive Review
Authors: Young Ian D. , Latousakis Dimitrios , Juge Nathalie
Published: April 2021

Polysaccharides such as β-2,1-linked fructans including inulin or fructose oligosaccharides are well-known prebiotics with recognised immunomodulatory properties. In recent years, other fructan types covering β-2,6-linked fructans, particularly microbial levans, have gained increasing interest in the field. β-2,6-linked fructans of different degrees of polymerisation can be synthesised by plants or microbes including those that reside in the gastrointestinal tract. Accumulating evidence suggests a role for these β-2,6 fructans in modulating immune function. Here, we provide an overview of the sources and structures of β-2,6 fructans from plants and microbes and describe their ability to modulate immune function in vitro and in vivo along with the suggested mechanisms underpinning their immunomodulatory properties. Further, we discuss the limitations and perspectives pertinent to current studies and the potential applications of β-2,6 fructans including in gut health.
Vitamin D Status in Spanish Elite Team Sport Players
Authors: Valtueña Jara , Aparicio-Ugarriza Raquel , Medina Daniel , Lizarraga Antonia , Rodas Gil , González-Gross Marcela , Drobnic Franchek
Published: April 2021

Low vitamin D is usual; however, data are limited for elite team players. The aim was to investigate the vitamin D levels in Football Club Barcelona (FCB) first division players of six sport modalities. Ninety-five elite male players (27.3 ± 4.6 y) belonging to FCB provided data for vitamin D throughout a season. In this study, 25(OH)D was measured in serum by chemiluminescent immunoassay. Outdoor/indoor training and supplementation were also considered. Total mean 25(OH)D concentrations were 91.9 ± 23.1 nmol/L in all players, with higher mean levels among supplemented players (94.7 ± 24.3 nmol/L). Around 25% of the team players were below optimal levels (<75 nmol/L), but none were below 50 nmol/L. Caucasian, supplemented football and handball players had the highest mean vitamin D concentrations over the whole year, whereas basketball players (indoor training) had the lowest ones. The highest rate of vitamin D insufficiency was found in spring (40%). A positive significant effect was observed for the interaction between indoor/outdoor training and supplementation with 25(OH)D concentrations (p < 0.05). Those team players training outdoors with supplementation had higher total vitamin D concentrations than those with indoors training and/or supplementation. A positive interaction of outdoor training with supplementation exists to determine 25(OH)D concentrations in team players.
Investigation on Anthrax in Bangladesh during the Outbreaks of 2011 and Definition of the Epidemiological Correlations
Authors: Galante Domenico , Manzulli Viviana , Serrecchia Luigina , Taranto Pietro Di , Hugh-Jones Martin , Hossain M. Jahangir , Rondinone Valeria , Cipolletta Dora , Pace Lorenzo , Iatarola Michela , Tolve Francesco , Aceti Angela , Poppa Elena , Fasanella Antonio
Published: April 2021

In 2011, in Bangladesh, 11 anthrax outbreaks occurred in six districts of the country. Different types of samples were collected from May to September in the six districts where anthrax had occurred in order to detect and type Bacillus anthracis (B. anthracis) strains. Anthrax was detected in 46.6% of the samples analysed, in particular in soils, but also in bone samples, water, animal feed, and rumen ingesta of dead animals. Canonical single nucleotide polymorphisms (CanSNPs) analysis showed that all the isolates belonged to the major lineage A, sublineage A.Br.001/002 of China and Southeast Asia while the multi-locus variable number of tandem repeats (VNTRs) analysis (MLVA) with 15 VNTRs demonstrated the presence of five genotypes, of which two resulted to be new genotypes. The single nucleotide repeats (SNRs) analysis showed 13 SNR types; nevertheless, due to its higher discriminatory power, the presence of two isolates with different SNR-type polymorphisms was detected within two MLVA genotypes. This study assumes that soil is not the only reason for the spread of the disease in Bangladesh; contaminated feed and water can also play an important role in the epidemiology of anthrax. Possible explanations for these epidemiological relationships are discussed.
Molecular Typing of Listeria monocytogenes IVb Serogroup Isolated from Food and Food Production Environments in Poland
Authors: Lachtara Beata , Osek Jacek , Wieczorek Kinga
Published: April 2021

Listeria monocytogenes is one of the most important foodborne pathogens that may be present in food and in food processing environments. In the present study, 91 L. monocytogenes isolates of serogroup IVb from raw meat, ready-to-eat food and food production environments in Poland were characterized by whole genome sequencing (WGS). The strains were also compared, using core genome multi-locus sequence typing (cgMLST) analysis, with 186 genomes of L. monocytogenes recovered worldwide from food, environments, and from humans with listeriosis. The L. monocytogenes examined belonged to three MLST clonal complexes: CC1 (10; 11.0% isolates), CC2 (70; 76.9%), and CC6 (11; 12.1%). CC1 comprised of two STs (ST1 and ST515) which could be divided into five cgMLST, CC2 covered two STs (ST2 and ST145) with a total of 20 cgMLST types, whereas CC6 consisted of only one ST (ST6) classified as one cgMLST. WGS sequences of the tested strains revealed that they had several pathogenic markers making them potentially hazardous for public health. Molecular comparison of L. monocytogenes strains tested in the present study with those isolated from food and human listeriosis showed a relationship between the isolates from Poland, but not from other countries.
Dual-Target Compounds against Type 2 Diabetes Mellitus: Proof of Concept for Sodium Dependent Glucose Transporter (SGLT) and Glycogen Phosphorylase (GP) Inhibitors
Authors: Sipos Ádám , Szennyes Eszter , Hajnal Nikolett Éva , Kun Sándor , Szabó Katalin E. , Uray Karen , Somsák László , Docsa Tibor , Bokor Éva
Published: April 2021

A current trend in the quest for new therapies for complex, multifactorial diseases, such as diabetes mellitus (DM), is to find dual or even multi-target inhibitors. In DM, the sodium dependent glucose cotransporter 2 (SGLT2) in the kidneys and the glycogen phosphorylase (GP) in the liver are validated targets. Several (β-D-glucopyranosylaryl)methyl (het)arene type compounds, called gliflozins, are marketed drugs that target SGLT2. For GP, low nanomolar glucose analogue inhibitors exist. The purpose of this study was to identify dual acting compounds which inhibit both SGLTs and GP. To this end, we have extended the structure-activity relationships of SGLT2 and GP inhibitors to scarcely known (C-β-D-glucopyranosylhetaryl)methyl arene type compounds and studied several (C-β-D-glucopyranosylhetaryl)arene type GP inhibitors against SGLT. New compounds, such as 5-arylmethyl-3-(β-D-glucopyranosyl)-1,2,4-oxadiazoles, 5-arylmethyl-2-(β-D-glucopyranosyl)-1,3,4-oxadiazoles, 4-arylmethyl-2-(β-D-glucopyranosyl)pyrimidines and 4(5)-benzyl-2-(β-D-glucopyranosyl)imidazole were prepared by adapting our previous synthetic methods. None of the studied compounds exhibited cytotoxicity and all of them were assayed for their SGLT1 and 2 inhibitory potentials in a SGLT-overexpressing TSA201 cell system. GP inhibition was also determined by known methods. Several newly synthesized (C-β-D-glucopyranosylhetaryl)methyl arene derivatives had low micromolar SGLT2 inhibitory activity; however, none of these compounds inhibited GP. On the other hand, several (C-β-D-glucopyranosylhetaryl)arene type GP inhibitor compounds with low micromolar efficacy against SGLT2 were identified. The best dual inhibitor, 2-(β-D-glucopyranosyl)-4(5)-(2-naphthyl)-imidazole, had a Ki of 31 nM for GP and IC50 of 3.5 μM for SGLT2. This first example of an SGLT-GP dual inhibitor can prospectively be developed into even more efficient dual-target compounds with potential applications in future antidiabetic therapy.
Sildenafil 4.0—Integrated Synthetic Chemistry, Formulation and Analytical Strategies Effecting Immense Therapeutic and Societal Impact in the Fourth Industrial Era
Authors: Ouranidis Andreas , Tsiaxerli Anastasia , Vardaka Elisavet , Markopoulou Catherine K. , Zacharis Constantinos K. , Nicolaou Ioannis , Hatzichristou Dimitris , Haidich Anna-Bettina , Kostomitsopoulos Nikolaos , Kachrimanis Kyriakos
Published: April 2021

Sildenafil is a potent selective, reversible inhibitor of phosphodiesterase type 5 (PDE5) approved for the treatment of erectile dysfunction and pulmonary arterial hypertension. Whilst twenty years have passed since its original approval by the US Food and Drug Administration (USFDA), sildenafil enters the fourth industrial era catalyzing the treatment advances against erectile dysfunction and pulmonary hypertension. The plethora of detailed clinical data accumulated and the two sildenafil analogues marketed, namely tadalafil and vardenafil, signify the relevant therapeutic and commercial achievements. The pharmacokinetic and pharmacodynamic behavior of the drug appears complex, interdependent and of critical importance whereas the treatment of special population cohorts is considered. The diversity of the available formulation strategies and their compatible administration routes, extend from tablets to bolus suspensions and from per os to intravenous, respectively, inheriting the associated strengths and weaknesses. In this comprehensive review, we attempt to elucidate the multi-disciplinary elements spanning the knowledge fields of chemical synthesis, physicochemical properties, pharmacology, clinical applications, biopharmaceutical profile, formulation approaches for different routes of administration and analytical strategies, currently employed to guide the development of sildenafil-based compositions.
Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer’s Disease
Authors: Cacabelos Ramón , Carril Juan , Corzo Lola , Fernández-Novoa Lucía , Pego Rocío , Cacabelos Natalia , Cacabelos Pablo , Alcaraz Margarita , Tellado Iván , Naidoo Vinogran
Published: April 2021

Background: Mood disorders represent a risk factor for dementia and are present in over 60% of cases with Alzheimer’s disease (AD). More than 80% variability in drug pharmacokinetics and pharmacodynamics is associated with pharmacogenetics. Methods: Anxiety and depression symptoms were assessed in 1006 patients with dementia (591 females, 415 males) and the influence of pathogenic (APOE) and metabolic (CYP2D6, CYP2C19, and CYP2C9) gene variants on the therapeutic outcome were analyzed after treatment with a multifactorial regime in a natural setting. Results and Conclusions: (i) Biochemical, hematological, and metabolic differences may contribute to changes in drug efficacy and safety; (ii) anxiety and depression are more frequent and severe in females than males; (iii) both females and males respond similarly to treatment, showing significant improvements in anxiety and depression; (iv) APOE-3 carriers are the best responders and APOE-4 carriers tend to be the worst responders to conventional treatments; and (v) among CYP2D6, CYP2C19, and CYP2C9 genophenotypes, normal metabolizers (NMs) and intermediate metabolizers (IMs) are significantly better responders than poor metabolizers (PMs) and ultra-rapid metabolizers (UMs) to therapeutic interventions that modify anxiety and depression phenotypes in dementia. APOE-4 carriers and CYP-related PMs and UMs deserve special attention for their vulnerability and poor response to current treatments.
Topical Antiseptic Formulations for Skin and Soft Tissue Infections
Authors: Hoang Thi Phuong Nga , Ghori Muhammad Usman , Conway Barbara R.
Published: April 2021

Skin and soft tissue infections (SSTIs) are usually acute conditions of inflammatory microbial occupation of the skin layers and underlying soft tissues. SSTIs are one of the most frequent types of infection, typically requiring medical intervention and contribute to morbidity and mortality in both primary care and hospitalised patients. Due to the dramatic rise of antibiotic resistance, antiseptic agents can be potential alternatives for the prevention and treatment of SSTIs. Notably, they are commonly recommended in many global practical guidelines for use in per- and post- operative procedures. A range of antiseptics, including chlorhexidine, triclosan, alcohol, and povidone-iodine, are used and are mainly formulated as traditional, simple dosage forms such as solutions and semi-solids. However, in recent years, there have been studies reporting the potential for nanotechnology in the delivery of antiseptics. In this review, we have collated the scientific literature that focuses on topical antiseptic formulations for prevention and treatment of SSTIs, and have divided findings into traditional and advanced formulations. We conclude that although nanotechnological formulations have demonstrated potential advantages for delivering drugs; nevertheless, there is still scope for traditional formulations and further development of optimised topical formulations to address the rise of antimicrobial resistance.
Dual Inhibition of P-gp and BCRP Improves Oral Topotecan Bioavailability in Rodents
Authors: Lee Jaeok , Kang Jiyeon , Kwon Na-Yun , Sivaraman Aneesh , Naik Ravi , Jin So-Young , Oh A. Reum , Shin Jae-Ho , Na Younghwa , Lee Kyeong , Lee Hwa-Jeong
Published: April 2021

P-glycoprotein (P-gp) inhibition has been studied to overcome multidrug resistance in cancer chemotherapy but failed in clinical trials due to low/toxic effects. Recently, a dual modulation of transporters and natural derivatives have been examined to surmount this limitation. We examined breast cancer resistance protein (BCRP) inhibition in vitro and in vivo by P-gp inhibitors derived from natural compounds in previous studies. P-gp inhibitors increased the accumulation of the anticancer drug, topotecan (TPT)—a substrate of P-gp and BCRP, albeit with higher affinity for BCRP—in BCRP-overexpressing cells, resulting in cell death. These dual inhibitors, when orally co-administered with TPT, enhanced TPT bioavailability with slightly reduced total oral clearance (Clt/F) in rats. In xenograft mice, they strengthened oral TPT-induced tumor reduction with no alterations in body weight. Moreover, we investigated the effects of an oral drug formulation (Cremophor® EL, Tween® 80, and polyethylene glycol 400) on the transporters function. The excipients increased TPT accumulation in P-gp- or BCRP-overexpressing cells. Oral TPT bioavailability was higher with the formulation than with a control, as shown by the increases in the maximum plasma concentration (Cmax) and the area under the plasma concentration–time curve from zero to infinity (AUCINF) (p< 0.01). Therefore, oral TPT bioavailability was enhanced by P-gp/BCRP dual inhibition, which resulted in a formulation-mediated increase in absorption and decrease in elimination, and a dual inhibitor-mediated decrease in elimination. These results suggest that the combination of dual inhibition by a natural derivative and the drug formulation can be a useful clinical approach.
A New Bevacizumab Carrier for Intravitreal Administration: Focus on Stability
Authors: Chirio Daniela , Peira Elena , Sapino Simona , Chindamo Giulia , Oliaro-Bosso Simonetta , Adinolfi Salvatore , Dianzani Chiara , Baratta Francesca , Gallarate Marina
Published: April 2021

Bevacizumab (BVZ) is a monoclonal antibody that binds to human vascular endothelial growth factor A (VEGF-A) and inhibits the interaction between VEGF-A and VEGF receptors, thus blocking the angiogenesis. Repeated intravitreal injections of BVZ for the treatment of ocular pathologies that present an excessive proliferation results in a low patience compliance. BVZ is specially indicated for the treatment of diabetic and degenerative retinopathy. In the present study, we designed lipid nanoparticles (NPs) as a BVZ sustained drug delivery system for reducing the frequency of administration. We used a simple and highly efficient procedure, “Cold dilution of microemulsions”, to obtain spherical NPs with mean diameters of 280–430 nm, Zeta potentials between −17 and −31 mV, and drug entrapment efficiencies between 50 to 90%. This study focused on the biochemical and biophysical stabilities of BVZ after entrapment in NPs. SDS-PAGE electrophoretic analysis and circular dichroism, dynamic light scattering, and scanning electron microscopy were used to characterize BVZ-loaded NPs. The biocompatibility was assessed by in vitro cell compatibility studies using the ARPE-19 cell line. Thus, in this work, a stable BVZ-loaded system was obtained. In addition, several studies have shown that BVZ is released slowly from the lipid matrix and that this system is biocompatible. The results are promising and the developed NPs could be exploited to create a new, potentially effective and minimally invasive treatment of intraocular diseases.
Convection Enhanced Delivery in the Setting of High-Grade Gliomas
Authors: Nwagwu Chibueze D. , Immidisetti Amanda V. , Jiang Michael Y. , Adeagbo Oluwasegun , Adamson David C. , Carbonell Anne-Marie
Published: April 2021

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood–brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.