bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Approach for the Search for Chemical Scaffolds with Activity at Both Acetylcholinesterase and the α7 Nicotinic Acetylcholine Receptor: A Perspective on Scaffolds with Dual Activity for the Treatment of Neurodegenerative Disorders
Authors: Kowal Natalia , Indurthi Dinesh , Ahring Philip , Chebib Mary , Olafsdottir Elin , Balle Thomas
Published: January 2019

Neurodegenerative disorders, including Alzheimer’s disease, belong to the group of the most difficult and challenging conditions with very limited treatment options. Attempts to find new drugs in most cases fail at the clinical stage. New tactics to develop better drug candidates to manage these diseases are urgently needed. It is evident that better understanding of the neurodegeneration process is required and targeting multiple receptors may be essential. Herein, we present a novel approach, searching for dual active compounds interacting with acetylcholinesterase (AChE) and the α7 nicotinic acetylcholine receptor (nAChR) using computational chemistry methods including homology modelling and high throughput virtual screening. Activities of identified hits were evaluated at the two targets using the colorimetric method of Ellman and two-electrode voltage-clamp electrophysiology, respectively. Out of 87,250 compounds from a ZINC database of natural products and their derivatives, we identified two compounds, 8 and 9, with dual activity and balanced IC50 values of 10 and 5 µM at AChE, and 34 and 14 µM at α7 nAChR, respectively. This is the first report presenting successful use of virtual screening in finding compounds with dual mode of action inhibiting both the AChE enzyme and the α7 nAChR and shows that computational methods can be a valuable tool in the early lead discovery process.
Microscopic Analyses of Fruit Cell Plastid Development in Loquat (Eriobotrya japonica) during Fruit Ripening
Authors: Lu Pengjun , Wang Ruqian , Zhu Changqing , Fu Xiumin , Wang Shasha , Grierson Don , Xu Changjie
Published: January 2019

Plastids are sites for carotenoid biosynthesis and accumulation, but detailed information on fruit plastid development and its relation to carotenoid accumulation remains largely unclear. Here, using Baisha (BS; white-fleshed) and Luoyangqing (LYQ; red-fleshed) loquat (Eriobotrya japonica), a detailed microscopic analysis of plastid development during fruit ripening was carried out. In peel cells, chloroplasts turned into smaller chromoplasts in both cultivars, and the quantity of plastids in LYQ increased by one-half during fruit ripening. The average number of chromoplasts per peel cell in fully ripe fruit was similar between the two cultivars, but LYQ peel cell plastids were 20% larger and had a higher colour density, associated with the presence of larger plastoglobules. In flesh cells, chromoplasts could be observed only in LYQ during the middle and late stages of ripening, and the quantity on a per-cell basis was higher than that in peel cells, but the size of chromoplasts was smaller. It was concluded that chromoplasts are derived from the direct conversion of chloroplasts to chromoplasts in the peel, and from de novo differentiation of proplastids into chromoplasts in flesh. The relationship between plastid development and carotenoid accumulation is discussed.
Metabolism and Biological Activities of 4-Methyl-Sterols
Authors: Darnet Sylvain , Schaller Hubert
Published: January 2019

4,4-Dimethylsterols and 4-methylsterols are sterol biosynthetic intermediates (C4-SBIs) acting as precursors of cholesterol, ergosterol, and phytosterols. Their accumulation caused by genetic lesions or biochemical inhibition causes severe cellular and developmental phenotypes in all organisms. Functional evidence supports their role as meiosis activators or as signaling molecules in mammals or plants. Oxygenated C4-SBIs like 4-carboxysterols act in major biological processes like auxin signaling in plants and immune system development in mammals. It is the purpose of this article to point out important milestones and significant advances in the understanding of the biogenesis and biological activities of C4-SBIs.
Vitamin C as a Modulator of the Response to Cancer Therapy
Authors: Blaszczak Wiktoria , Barczak Wojciech , Masternak Julia , Kopczyński Przemysław , Zhitkovich Anatoly , Rubiś Błażej
Published: January 2019

Ascorbic acid (vitamin C) has been gaining attention as a potential treatment for human malignancies. Various experimental studies have shown the ability of pharmacological doses of vitamin C alone or in combinations with clinically used drugs to exert beneficial effects in various models of human cancers. Cytotoxicity of high doses of vitamin C in cancer cells appears to be related to excessive reactive oxygen species generation and the resulting suppression of the energy production via glycolysis. A hallmark of cancer cells is a strongly upregulated aerobic glycolysis, which elevates its relative importance as a source of ATP (Adenosine 5′-triphosphate). Aerobic glycolysis is maintained by a highly increased uptake of glucose, which is made possible by the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and GLUT-4. These proteins can also transport the oxidized form of vitamin C, dehydroascorbate, permitting its preferential uptake by cancer cells with the subsequent depletion of critical cellular reducers as a result of ascorbate formation. Ascorbate also has a potential to affect other aspects of cancer cell metabolism due to its ability to promote reduction of iron(III) to iron(II) in numerous cellular metalloenzymes. Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C can be beneficial by itself and promote activity of specific drugs.
Synergistic Effects of The Enhancements to Mitochondrial ROS, p53 Activation and Apoptosis Generated by Aspartame and Potassium Sorbate in HepG2 Cells
Authors: Qu Daofeng , Jiang Mengxue , Huang Dongping , Zhang Hui , Feng Lifang , Chen Yuewen , Zhu Xuan , Wang Suhua , Han Jianzhong
Published: January 2019

The safety of food additives has been widely concerned. Using single additives in the provisions of scope is safe, but the combination of additives, may induce additive, synergy, antagonism and other joint effects. This study investigated the cytotoxicity of aspartame (AT) together with potassium sorbate (PS). Thiazolyl Blue Tetrazolium Bromide (MTT) assay indicated that AT and PS had IC50 values of 0.48 g/L and 1.25 g/L at 24 h, respectively. High content analysis (HCA) showed that both AT and PS had a negative effect on mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and DNA damage while the joint group behaved more obviously. The biochemical assays revealed typical cell morphological changes and the activation of cytochrome c and caspase-3 verified apoptosis induced by AT together with PS. With dissipation of MMP and increase of cell membrane permeability (CMP), it indicated AT together with PS-induced apoptosis was mediated by mitochondrial pathway. Meanwhile, p53 were involved in DNA damage, and the ratio of Bax/Bcl-2 was increased. Moreover, excessive ROS induced by AT together with PS is a key initiating factor for apoptosis. All these results proved that p53 was involved in apoptosis via mitochondria-mediated pathway and the process was regulated by ROS.
Exploratory Cortex Metabolic Profiling Revealed the Sedative Effect of Amber in Pentylenetetrazole-Induced Epilepsy-Like Mice
Authors: Zhu Zhenhua , Chen Chenkai , Zhu Yue , Shang Erxin , Zhao Ming , Guo Sheng , Guo Jianming , Qian Dawei , Tang Zhishu , Yan Hui , Duan Jinao
Published: January 2019

Epilepsy is a common clinical syndrome characterized by sudden and recurrent attacks and temporary central nervous system dysfunction caused by excessive discharge of neurons in the brain. Amber, a fossilized organic substance formed by the resins of conifers and leguminous plants, was prescribed to tranquilize the mind in China. In this paper, the antiepileptic effect of amber was evaluated by a pentylenetetrazole (PTZ)-induced epileptic model. An untargeted metabolomics approach was applied to investigate metabolic changes in the epileptic model, which was based on HILIC-UHPLC-MS/MS multivariate statistical analysis and metabolism network analysis. The outcome of this study suggested that 35 endogenous metabolites showed marked perturbations. Moreover, four metabolism pathways were mainly involved in epilepsy. After treatment by amber, the endogenous metabolites had a marked tendency to revert back to the situation of the control group which was consistent with phenobarbital. This study characterized the pentylenetetrazole-induced epileptic model and provided new evidence for the sedative effect of amber.
Efficient Tandem Addition/Cyclization for Access to 2,4-Diarylquinazolines via Catalytic Carbopalladation of Nitriles
Authors: Gong Julin , Hu Kun , Zhang Yetong , Shao Yinlin , Cheng Tianxing , Hu Maolin , Chen Jiuxi
Published: January 2019

The first example of the palladium-catalyzed tandem addition/cyclization of 2-(benzylidenamino)benzonitriles with arylboronic acids has been developed. This transformation features good functional group tolerance and provides an alternative synthetic pathway to access 2,4-diarylquinazolines in moderate to good yields. A plausible mechanism for the formation of 2,4-diarylquinazolines involving sequential nucleophilic addition followed by an intramolecular cyclization is proposed.
Preparation of Herbal Formulation for Inflammatory Bowel Disease Based on In Vitro Screening and In Vivo Evaluation in a Mouse Model of Experimental Colitis
Authors: Lee Jaemin , Choi Han-Seok , Lee Jinkyung , Park Jimin , Kim Sang-Back , Shin Myoung-Sook , Lee Sullim , Hwang Gwi Seo , Koo Bon Am , Kang Ki Sung
Published: January 2019

Many medicinal plants have been used traditionally in East Asia for the treatment of gastrointestinal disease and inflammation. The aim of this study was to evaluate the anti-inflammatory activity of 350 extracts (175 water extracts and 175 ethanol extracts) from 71 single plants, 97 mixtures of two plants, and seven formulations based on traditional medicine, to find herbal formulations to treat inflammatory bowel disease (IBD). In the in vitro screening, nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels were determined in LPS-treated RAW264.7 cells and the TNF-α induced monocyte-epithelial cell adhesion assay was used for the evaluation of the anti-inflammatory activity of the compounds. Dextran sulfate sodium (DSS)-induced colitis model and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model were used to evaluate the therapeutic effect against IBD of the samples selected from the in vitro screening. KM1608, composed of Zingiber officinale, Terminalia chebula and Aucklandia lappa, was prepared based on the screening experiments. The oral administration of KM1608 significantly attenuated the severity of colitis symptoms, such as weight loss, diarrhea, and rectal bleeding, in TNBS-induced colitis. In addition, inflammatory mediators, such as myeloperoxidase, TNF-α, and IL-6 levels decreased in the lysate of colon tissues treated with KM1608. Collectively, KM1608 ameliorated colitis through the regulation of inflammatory responses within the colon, which indicated that KM1608 had potential for the treatment of IBD.
Astilbin Inhibits the Activity of Sortase A from Streptococcus mutans
Authors: Wang Junxian , Shi Yan , Jing Shisong , Dong Haisi , Wang Dacheng , Wang Tiedong
Published: January 2019

Streptococcus mutans (S. mutans) is the primary etiological agent of dental caries. The S. mutans enzyme sortase A (SrtA) is responsible for anchoring bacterial cell wall surface proteins involved in host cell attachment and biofilm formation. Thus, SrtA is an attractive target for inhibiting dental caries caused by S. mutans-associated acid fermentation. In this study, we observed that astilbin, a flavanone compound extracted from Rhizoma Smilacis Glabrae, has potent inhibitory activity against the S. mutans SrtA, with an IC50 of 7.5 μg/mL. In addition, astilbin was proven to reduce the formation of biofilm while without affecting the growth of S. mutans. The results of a molecular dynamics simulation and a mutation analysis revealed that the Arg213, Leu111, and Leu116 of SrtA are important for the interaction between SrtA and astilbin. The results of this study demonstrate the potential of using astilbin as a nonbactericidal agent to modulate pathogenicity of S. mutans by inhibiting the activity of SrtA.
Supercritical Fluid Extraction of Carotenoids from Vegetable Waste Matrices
Authors: de Andrade Lima Micael , Kestekoglou Ioannis , Charalampopoulos Dimitris , Chatzifragkou Afroditi
Published: January 2019

The aim of this work was to evaluate a previously-developed model on supercritical fluid extraction (SFE) for carotenoid recovery from carrot peels on various carotenoid-rich fruit and vegetable wastes. To this end, 15 matrices, including flesh and peels of sweet potato, tomato, apricot, pumpkin and peach, as well as flesh and wastes of green, yellow and red peppers, were submitted to SFE under optimised conditions (59 °C, 350 bar, 15 g/min CO2, 15.5% (v/v) ethanol as co-solvent, 30 min of extraction time). The obtained extracts were characterised for their total carotenoid content, antioxidant activity and total carotenoid recovery (TCR). TCR values were greater than 90% w/w for most samples, with β-carotene being the most successfully extracted compound (TCRs 88–100% w/w). More polar carotenoids, such as lutein and lycopene, exhibited lower TCRs. A comparison with literature data suggested that carotenoid extraction is partially dependent on the composition of vegetable matrices, specifically on polysaccharide and moisture content. The results indicated that the optimised SFE conditions can be used as a general model for carotenoid extraction from various fruit and vegetable matrices and as a viable method for adding value to these waste streams by generating carotenoid-rich extracts.
Proof of an Outer Membrane Target of the Efflux Inhibitor Phe-Arg-β-Naphthylamide from Random Mutagenesis
Authors: Schuster Sabine , Bohnert Jürgen A. , Vavra Martina , Rossen John W. , Kern Winfried V.
Published: January 2019

Phe-Arg-β-naphthylamide (PAβN) has been characterized as an efflux pump inhibitor (EPI) acting on the major multidrug resistance efflux transporters of Gram-negative bacteria, such as AcrB in Eschericha coli. In the present study, in vitro random mutagenesis was used to evolve resistance to the sensitizing activity of PAβN with the aim of elucidating its mechanism of action. A strain was obtained that was phenotypically similar to a previously reported mutant from a serial selection approach that had no efflux-associated mutations. We could confirm that acrB mutations in the new mutant were unrelated to PAβN resistance. The next-generation sequencing of the two mutants revealed loss-of-function mutations in lpxM. An engineered lpxM knockout strain showed up to 16-fold decreased PAβN activity with large lipophilic drugs, while its efflux capacity, as well as the efficacy of other EPIs, remained unchanged. LpxM is responsible for the last acylation step in lipopolysaccharide (LPS) synthesis, and lpxM deficiency has been shown to result in penta-acylated instead of hexa-acylated lipid A. Modeling the two lipid A types revealed steric conformational changes due to underacylation. The findings provide evidence of a target site of PAβN in the LPS layer, and prove membrane activity contributing to its drug-sensitizing potency.
Liposomal Taro Lectin Nanocapsules Control Human Glioblastoma and Mammary Adenocarcinoma Cell Proliferation
Authors: Corrêa Anna C. N. T. F. , Vericimo Mauricio A. , Dashevskiy Andriy , Pereira Patricia R. , Paschoalin Vania M. F.
Published: January 2019

The search for natural anticancer agents and nanocarrier uses are a part of the current strategies to overcome the side effects caused by chemotherapeutics. Liposomal nanocapsules loaded with purified tarin, a potential immunomodulatory and antitumoral lectin found in taro corms, were produced. Liposomes were composed by 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine, cholesterylhemisuccinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000 prepared by thin-film hydration. Small unilamellar vesicles were achieved by sonication and extrusion. Scanning electron microscopy evidenced round-shaped nanocapsules presenting a smooth surface, 150 nm diameter and polydispersity index <0.2, estimated by dynamic light scattering. Tarin entrapment rates were over 80% and leakage of ~3% under 40 days of storage at 4 °C. Entrapped tarin exhibited an 83% release after 6 h at pH 4.6–7.4 and 36 °C. Both free and encapsulated tarin exhibited no in vitro toxicity against healthy mice bone marrow and L929 cells but stimulated the production of fibroblast-like and large round-shaped cells. Encapsulated tarin resulted in inhibition of human glioblastoma (U-87 MG) and breast adenocarcinoma (MDA-MB-231) proliferation, with an IC50 of 39.36 and 71.38 µg/mL, respectively. The effectiveness of encapsulated tarin was similar to conventional chemotherapy drugs, such as cisplatin and temozolide. Tarin liposomal nanocapsules exhibited superior pharmacological activity compared to free tarin as a potential chemotherapy adjuvant.
Pectin and Neutral Monosaccharides Production during the Simultaneous Hydrothermal Extraction of Waste Biomass from Refining of Sugar—Optimization with the Use of Doehlert Design
Authors: Pińkowska Hanna , Krzywonos Małgorzata , Wolak Paweł , Złocińska Adrianna
Published: January 2019

We propose a one-stage hydrothermal extraction of sugar beet pulp leading to effective co-production of pectin and neutral monosaccharides with a relatively high yield and satisfactory purity without the presence of an acidic catalyst. The optimal experimental design methodology was used for modelling and optimizing the yield of pectin and neutral monosaccharides. In good agreement with experimental results (R2 = 0.955), the model predicts an optimal yield of pectin (approx. 121.1 g kg−1 ± 0.47 g kg−1) at a temperature and time of about 118.1 °C and 21.5 min, respectively. The highest yield of the sum of neutral monosaccharides (approx. 82.6 g kg−1 ± 0.72 g kg−1) was obtained at about 116.2 °C and 26.4 min (R2 = 0.976). The obtained results are suitable for industrial upscaling and may provide an incentive to implement a new, environmentally friendly, simple, and effective method for treating waste product from the sugar refining industry, which has proved onerous until now.
Ripe and Raw Pu-Erh Tea: LC-MS Profiling, Antioxidant Capacity and Enzyme Inhibition Activities of Aqueous and Hydro-Alcoholic Extracts
Authors: Roda Gabriella , Marinello Cristina , Grassi Anita , Picozzi Claudia , Aldini Giancarlo , Carini Marina , Regazzoni Luca
Published: January 2019

Herein, we reported a detailed profiling of soluble components of two fermented varieties of Chinese green tea, namely raw and ripe pu-erh. The identification and quantification of the main components was carried out by means of mass spectrometry and UV spectroscopy, after chromatographic separation. The antioxidant capacity towards different radical species, the anti-microbial and the enzyme inhibition activities of the extracts were then correlated to their main constituents. Despite a superimposable qualitative composition, a similar caffeine content, and similar enzyme inhibition and antimicrobial activities, raw pu-erh tea extract had a better antioxidant capacity owing to its higher polyphenol content. However, the activity of raw pu-erh tea seems not to justify its higher production costs and ripe variety appears to be a valid and low-cost alternative for the preparation of products with antioxidant or antimicrobial properties.
Rare Acetogenins with Anti-Inflammatory Effect from the Red Alga Laurencia obtusa
Authors: Alarif Walied Mohamed , Al-Lihaibi Sultan Semran , Bawakid Nahed Obaid , Abdel-Lateff Ahmed , Al-malky Hamdan Salem
Published: January 2019

Three new rare C12 acetogenins (enyne derivatives 1–3) were isolated from the organic extract obtained from the red alga Laurencia obtusa, collected from the Red Sea. The chemical structures of the isolated compounds were established by spectroscopical data analyses. Potent anti-inflammatory effect of the isolated metabolites was evidenced by inhibition of the release of inflammatory mediators (e.g., TNF-α, IL-1β and IL-6) by employing Human Peripheral Blood Mononuclear Cells (PBMC).
A Spotlight on Viruses—Application of Click Chemistry to Visualize Virus-Cell Interactions
Authors: Müller Thorsten G. , Sakin Volkan , Müller Barbara
Published: January 2019

The replication of a virus within its host cell involves numerous interactions between viral and cellular factors, which have to be tightly controlled in space and time. The intricate interplay between viral exploitation of cellular pathways and the intrinsic host defense mechanisms is difficult to unravel by traditional bulk approaches. In recent years, novel fluorescence microscopy techniques and single virus tracking have transformed the investigation of dynamic virus-host interactions. A prerequisite for the application of these imaging-based methods is the attachment of a fluorescent label to the structure of interest. However, their small size, limited coding capacity and multifunctional proteins render viruses particularly challenging targets for fluorescent labeling approaches. Click chemistry in conjunction with genetic code expansion provides virologists with a novel toolbox for site-specific, minimally invasive labeling of virion components, whose potential has just recently begun to be exploited. Here, we summarize recent achievements, current developments and future challenges for the labeling of viral nucleic acids, proteins, glycoproteins or lipids using click chemistry in order to study dynamic processes in virus-cell interactions.
Momilactones A and B Are α-Amylase and α-Glucosidase Inhibitors
Authors: Quan Nguyen Van , Tran Hoang-Dung , Xuan Tran Dang , Ahmad Ateeque , Dat Tran Dang , Khanh Tran Dang , Teschke Rolf
Published: January 2019

Momilactones A (MA) and B (MB) are the active phytoalexins and allelochemicals in rice. In this study, MA and MB were purified from rice husk of Oryza sativa cv. Koshihikari by column chromatography, and purification was confirmed by high-performance liquid chromatography, thin-layer chromatography, gas chromatography-mass spectrometry, liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), and 1H and 13C nuclear magnetic resonance analyses. By in vitro assays, both MA and MB exerted potent inhibition on α-amylase and α-glucosidase activities. The inhibitory effect of MB on these two key enzymes was greater than that of MA. Both MA and MB exerted greater α-glucosidase suppression as compared to that of the commercial diabetic inhibitor acarbose. Quantities of MA and MB in rice grain were 2.07 ± 0.01 and 1.06 ± 0.01 µg/dry weight (DW), respectively. This study was the first to confirm the presence of MA and MB in refined rice grain and reported the α-amylase and α-glucosidase inhibitory activity of the two compounds. The improved protocol of LC-ESI-MS in this research was simple and effective to detect and isolate MA and MB in rice organs.
Antiradical and Antioxidative Activity of Azocalix[4]arene Derivatives: Combined Experimental and Theoretical Study
Authors: Ni Jiaqi , Lu Lilin , Liu Yi
Published: January 2019

Developing antioxidants with high efficiency is fundamentally important for the protection of living cells and engineering materials against oxidative damage. In this present study, two azocalix[4]arene derivatives were synthesized via a diazo coupling reaction between calix[4]arene and diazonium salts. Their antiradical and antioxidative performances were evaluated by hydroxyl radical scavenging and pyrogallol autoxidation inhibition experiments. Combined with theoretical studies, the antiradical and antioxidative mechanisms have been explored. The results demonstrated that these two azocalix[4]arene derivatives both exhibited remarkable antiradical and antioxidative activity. The macrocyclic framework of the calix[4]arene and para-azo substituent group at the upper rim of calix[4]arene contributed synergistically and importantly to its excellent antiradical and antioxidant activity.
Polar Metallocenes
Authors: Zhang Haiwu , Yavorsky B.Yu. , Cohen R.E.
Published: January 2019

Crystalline polar metallocenes are potentially useful active materials as piezoelectrics, ferroelectrics, and multiferroics. Within density functional theory (DFT), we computed structural properties, energy differences for various phases, molecular configurations, and magnetic states, computed polarizations for different polar crystal structures, and computed dipole moments for the constituent molecules with a Wannier function analysis. Of the systems studied, Mn2(C9H9N)2 is the most promising as a multiferroic material, since the ground state is both polar and ferromagnetic. We found that the predicted crystalline polarizations are 30–40% higher than the values that would be obtained from the dipole moments of the isolated constituent molecules, due to the local effects of the self-consistent internal electric field, indicating high polarizabilities.
Novel Applications of Lead Acetate and Flow Cytometry Methods for Detection of Sulfur-Containing Molecules
Authors: Anishchenko Evgeniya , Vigorito Carmela , Mele Luigi , Lombari Patrizia , Perna Alessandra F. , Ingrosso Diego
Published: February 2019

Hydrogen sulfide (H2S) is the most recently established gaseous vasodilator, enzymatically produced from cysteine metabolism, involved in a number of pathophysiological processes. However, its accurate detection in vivo is critical due to its volatility and tendency to form sulfane sulfur derivatives, thus limiting the data interpretation of its biological roles. We developed new applications of the simple and rapid method to measure H2S release in cell culture systems, based on the lead acetate strip test. This test, previously prevalently used in microbiology, was compared with the agar trap method, applied, in parallel, on both cell cultures and cell-free samples. Sulfane sulfur represents the major species derived from intracellular H2S. Various fluorescent probes are available for quantitation of H2S derivatives intracellularly. We present here an alternative to the classic imaging method for sulfane sulfur evaluation, running on a flow cytometer, based on SSP4 probe labeling. Flow cytometry turned out to be more direct, fully quantitative and less time-consuming compared to microscopy and more precise with respect to the fluorescence multi-plate reader assay. The new application methods for H2S determination appear to be fully suitable for the analysis of H2S release and sulfane sulfur content in biological samples.
Critical Admission Temperature of H2 and CH4 in Nanopores of Exchanged ERI Zeolites
Authors: Quiroz-Estrada Karla , Hernández Miguel Ángel , Felipe-Mendoza Carlos , Santamaría-Juárez Juana Deisy , Petranovskii Vitalii , Rubio Efraín
Published: January 2019

Due to the nanoporous nature of zeolitic materials, they can be used as gas adsorbents. This paper describes the effect of critical admission temperature through narrow pores of natural ERI zeolites at low levels of coverage. This phenomenon occurs by adsorption of CH4 and H2 on pores in natural erionite. The zeolite was exchanged with aqueous solutions of Na+, Mg2+, and Ca2+ salts at different concentrations, times, and temperatures of treatment. Experimental data of CH4 and H2 adsorption were treated by the Langmuir equation. Complementarily, the degree of interaction of these gases with these zeolites was evaluated by the evolution of isosteric heats of adsorption. The Ca2+ and Mg2+ cations favor the adsorption phenomena of H2 and CH4. These cations occupy sites in strategic positions Ca1, Ca2, and Ca3, which are located in the nanocavities of erionite zeolites and K2 in the center of 8MR. Following the conditions of temperature and the exchange treatment, ERICa2 and ERINa3 samples showed the best behavior for CH4 and H2 adsorption.
High Sensitivity Surface Plasmon Resonance Sensor Based on Two-Dimensional MXene and Transition Metal Dichalcogenide: A Theoretical Study
Authors: Xu Yi , Ang Yee Sin , Wu Lin , Ang Lay Kee
Published: January 2019

MXene, a new class of two-dimensional nanomaterials, have drawn increasing attention as emerging materials for sensing applications. However, MXene-based surface plasmon resonance sensors remain largely unexplored. In this work, we theoretically show that the sensitivity of the surface plasmon resonance sensor can be significantly enhanced by combining two-dimensional Ti 3 C 2 T x MXene and transition metal dichalcogenides. A high sensitivity of 198 ∘ /RIU (refractive index unit) with a sensitivity enhancement of 41.43% was achieved in aqueous solutions (refractive index ∼1.33) with the employment of monolayer Ti 3 C 2 T x MXene and five layers of WS 2 at a 633 nm excitation wavelength. The integration of Ti 3 C 2 T x MXene with a conventional surface plasmon resonance sensor provides a promising approach for bio- and chemical sensing, thus opening up new opportunities for highly sensitive surface plasmon resonance sensors using two-dimensional nanomaterials.
Prediction of Gold Nanoparticle and Microwave-Induced Hyperthermia Effects on Tumor Control via a Simulation Approach
Authors: Dimitriou Nikolaos M. , Pavlopoulou Athanasia , Tremi Ioanna , Kouloulias Vassilis , Tsigaridas Georgios , Georgakilas Alexandros G.
Published: January 2019

Hyperthermia acts as a powerful adjuvant to radiation therapy and chemotherapy. Recent advances show that gold nanoparticles (Au-NPs) can mediate highly localized thermal effects upon interaction with laser radiation. The purpose of the present study was to investigate via in silico simulations the mechanisms of Au-NPs and microwave-induced hyperthermia, in correlation to predictions of tumor control (biological endpoints: tumor shrinkage and cell death) after hyperthermia treatment. We also study in detail the dependence of the size, shape and structure of the gold nanoparticles on their absorption efficiency, and provide general guidelines on how one could modify the absorption spectrum of the nanoparticles in order to meet the needs of specific applications. We calculated the hyperthermia effect using two types of Au-NPs and two types of spherical tumors (prostate and melanoma) with a radius of 3 mm. The plasmon peak for the 30 nm Si-core Au-coated NPs and the 20 nm Au-NPs was found at 590 nm and 540 nm, respectively. Considering the plasmon peaks and the distribution of NPs in the tumor tissue, the induced thermal profile was estimated for different intervals of time. Predictions of hyperthermic cell death were performed by adopting a three-state mathematical model, where “three-state” includes (i) alive, (ii) vulnerable, and (iii) dead states of the cell, and it was coupled with a tumor growth model. Our proposed methodology and preliminary results could be considered as a proof-of-principle for the significance of simulating accurately the hyperthermia-based tumor control involving the immune system. We also propose a method for the optimization of treatment by overcoming thermoresistance by biological means and specifically through the targeting of the heat shock protein 90 (HSP90), which plays a critical role in the thermotolerance of cells and tissues.
Black Phosphorus Nano-Polarizer with High Extinction Ratio in Visible and Near-Infrared Regime
Authors: Shen Wanfu , Hu Chunguang , Huo Shuchun , Sun Zhaoyang , Fan Guofang , Liu Jing , Sun Lidong , Hu Xiaotang
Published: January 2019

We study computationally the design of a high extinction ratio nano polarizer based on black phosphorus (BP). A scattering-matrix calculation method is applied to compute the overall polarization extinction ratio along two orthogonal directions. The results reveal that, with a resonance cavity of SiO2, both BP/ SiO 2 /Si and h-BN/BP/ SiO 2 /Si configurations can build a linear polarizer with extinction ratio higher than 16 dB at a polarized wavelength in the range of 400 nm–900 nm. The polarization wavelength is tunable by adjusting the thickness of the BP layer while the thicknesses of the isotrocpic layers are in charge of extinction ratios. The additional top layer of h-BN was used to prevent BP degradation from oxidation and strengthens the practical applications of BP polarizer. The study shows that the BP/ SiO 2 /Si structure, with a silicon compatible and easy-to-realize method, is a valuable solution when designing polarization functional module in integrated photonics and optical communications circuits.
Effect of Commercially Available Sugar-Sweetened Beverages on Subjective Appetite and Short-Term Food Intake in Boys
Authors: Poirier Kelly L. , Totosy de Zepetnek Julia O. , Bennett Lorianne J. , Brett Neil R. , Boateng Terence , Schwartz Alexander , Luhovyy Bohdan L. , Bellissimo Nick
Published: January 2019

It is unclear whether sugar sweetened beverages bypass regulatory controls of food intake (FI) in boys. The objective of the present study was to determine the effects of isovolumetric preloads (350 mL) of a fruit-flavoured drink (154 kcal), cola (158 kcal), 1% M.F. chocolate milk (224 kcal), and water (0 kcal) on subjective appetite and FI in boys aged 9–14 years. On four separate mornings, boys consumed one of the preloads in a random order; subjective appetite was measured at 15 min intervals, and FI was measured via an ad libitum pizza lunch at 60 min post-beverage consumption. In the 32 boys (age: 11.8 ± 0.3 years), FI was reduced (p < 0.001) after cola (940 ± 46 kcal) and chocolate milk (878 ± 41 kcal) compared with the water control (1048 ± 35 kcal) and after chocolate milk compared to the fruit drink (1005 ± 44 kcal). Cumulative FI after the fruit drink was greater than the water control (1159 ± 44 vs. 1048 ± 35 kcal; p = 0.03). Average appetite was not affected by the treatment, but the cola treatment resulted in greater fullness (p = 0.04) and lower prospective food consumption (p = 0.004) compared with the fruit drink. In conclusion, chocolate milk and cola suppressed next-meal FI at 60 min, while fruit drink increased cumulative FI (beverage + next meal) over 60 min in boys. Results from this study suggest that beverage composition is an important determinant of FI suppression in boys.
Anti-Inflammatory Effect of Chloroform Fraction of Pyrus Ussuriensis Maxim. Leaf Extract on 2, 4-Dinitrochlorobenzene-Induced Atopic Dermatitis in nc/nga Mice
Authors: Cho KyoHee , Kang Min , Parveen Amna , Yumnam Silvia , Kim Sun
Published: January 2019

Pyrus ussuriensis Maxim, a pear commonly known as “Sandolbae” in Korea, is used as a traditional herbal medicine for asthma, cough, and fever in Korea, China, and Japan. P. ussuriensis Maxim leaves (PUL) have therapeutic effects on atopic dermatitis (AD). However, there are no reports on the efficacy of specific components of PUL. In the present study, activity-guided isolation of PUL was used to determine the compounds with potent activity. Astragalin was identified as the major component of the chloroform-soluble fraction of PUL (PULC) using High-performance liquid chromatography (HPLC) analysis. Astragalin and PULC were tested in vitro and in vivo for their effects against AD. PULC and astragalin dose-dependently inhibited the production of nitric oxide (NO) in mouse macrophage (RAW 264.7) cells, and interleukin (IL)-6 and IL-1β in tumor necrosis factor (TNF-α)/interferon γ (IFNγ) induced HaCaT cells. In the AD mice model, PULC and astragalin application significantly reduced dermatitis severity, scratching behavior, and trans-epidermal water loss (TEWL) when compared to that of 2, 4-dinitrochlorobenzene-treated NC/Nga mice. Additionally, they normalized skin barrier function by decreasing immunoglobulin E (IgE) levels in the serum. Filaggrin and involucrin protein levels were normalized by PULC treatment in HaCaT cells and skin lesions. These results indicate that PULC and astragalin ameliorate AD-like symptoms by alleviating both pro-inflammatory cytokines and immune stimuli in vitro and in vivo in animal models. Therefore, PULC and astragalin might be effective therapeutic agents for the treatment of AD.
The Impact of Ramadan Fasting on the Reduction of PASI Score, in Moderate-To-Severe Psoriatic Patients: A Real-Life Multicenter Study
Authors: Damiani Giovanni , Watad Abdulla , Bridgewood Charlie , Pigatto Paolo Daniele Maria , Pacifico Alessia , Malagoli Piergiorgio , Bragazzi Nicola Luigi , Adawi Mohammad
Published: January 2019

Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the “Psoriasis Area and Severity Index” (PASI) score after the Ramadan fasting (mean difference = −0.89 ± 1.21, p < 0.0001) was found. At the multivariate regression, the use of cyclosporine (p = 0.0003), interleukin-17 or IL-17 blockers (p < 0.0001), and tumor necrosis factor or TNF blockers (p = 0.0107) was independently associated with a low PASI score, while the use of apremilast (p = 0.0009), and phototherapy (p = 0.0015) was associated with a high PASI score before the Ramadan fasting. Similarly, the consumption of cyclosporine (p < 0.0001), IL-17 blockers (p < 0.0001), mammalian target of rapamycin or mTOR inhibitors (p = 0.0081), and TNF blockers (p = 0.0017) predicted a low PASI score after the Ramadan fasting. By contrast, narrow band ultraviolet light B or NB-UVB (p = 0.0015) was associated with a high PASI score after Ramadan fasting. Disease duration (p = 0.0078), use of apremilast (p = 0.0005), and of mTOR inhibitors (p = 0.0034) were independent predictors of the reduction in the PASI score after the Ramadan fasting. These findings reflect the influence of dieting strategy, the biological clock, and circadian rhythm on the treatment of plaque psoriasis.
3,5-Diiodo-L-Thyronine Exerts Metabolically Favorable Effects on Visceral Adipose Tissue of Rats Receiving a High-Fat Diet
Authors: Silvestri Elena , Senese Rosalba , Cioffi Federica , De Matteis Rita , Lattanzi Davide , Lombardi Assunta , Giacco Antonia , Salzano Anna Maria , Scaloni Andrea , Ceccarelli Michele , Moreno Maria , Goglia Fernando , Lanni Antonia , de Lange Pieter
Published: January 2019

When administered to rats receiving a high-fat diet (HFD), 3,5-diiodo-L-thyronine (3,5-T2) [at a dose of 25 μg/100 g body weight (BW)] is known to increase energy expenditure and to prevent HFD-induced adiposity. Here, we investigated which cellular and molecular processes in visceral white adipose tissue (VAT) contributed to the beneficial effect of 3,5-T2 over time (between 1 day and 4 weeks following administration). 3,5-T2 programmed the adipocyte for lipolysis by rapidly inducing hormone sensitive lipase (HSL) phosphorylation at the protein kinase A-responsive site Ser563, accompanied with glycerol release at the 1-week time-point, contributing to the partial normalization of adipocyte volume with respect to control (N) animals. After two weeks, when the adipocyte volumes of HFD-3,5-T2 rats were completely normalized to those of the controls (N), 3,5-T2 consistently induced HSL phosphorylation at Ser563, indicative of a combined effect of 3,5-T2-induced adipose lipolysis and increasing non-adipose oxidative metabolism. VAT proteome analysis after 4 weeks of treatment revealed that 3,5-T2 significantly altered the proteomic profile of HFD rats and produced a marked pro-angiogenic action. This was associated with a reduced representation of proteins involved in lipid storage or related to response to oxidative stress, and a normalization of the levels of those involved in lipogenesis-associated mitochondrial function. In conclusion, the prevention of VAT mass-gain by 3,5-T2 occurred through different molecular pathways that, together with the previously reported stimulation of resting metabolism and liver fatty acid oxidation, are associated with an anti adipogenic/lipogenic potential and positively impact on tissue health.
Association of Vegetarian Diet with Chronic Kidney Disease
Authors: Liu Hao-Wen , Tsai Wen-Hsin , Liu Jia-Sin , Kuo Ko-Lin
Published: January 2019

Chronic kidney disease (CKD) and its complications are major global public health issues. Vegetarian diets are associated with a more favorable profile of metabolic risk factors and lower blood pressure, but the protective effect in CKD is still unknown. We aim to assess the association between vegetarian diets and CKD. A cross-sectional study was based on subjects who received physical checkups at the Taipei Tzu Chi Hospital from 5 September 2005, to 31 December 2016. All subjects completed a questionnaire to assess their demographics, medical history, diet pattern, and lifestyles. The diet patterns were categorized into vegan, ovo-lacto vegetarian, or omnivore. CKD was defined as an estimated GFR <60 mL/min/1.73 m2 or the presence of proteinuria. We evaluated the association between vegetarian diets and CKD prevalence by using multivariate analysis. Our study recruited 55,113 subjects. CKD was significantly less common in the vegan group compared with the omnivore group (vegan 14.8%, ovo-lacto vegetarians 20%, and omnivores 16.2%, P < 0.001). The multivariable logistic regression analysis revealed that vegetarian diets including vegan and ovo-lacto vegetarian diets were possible protective factors [odds ratios = 0.87 (0.77–0.99), P = 0.041; 0.84 (0.78–0.90), P < 0.001]. Our study showed a strong negative association between vegetarian diets and prevalence of CKD. If such associations are causal, vegetarian diets could be helpful in reducing the occurrence of CKD.
Utilizing Dietary Nutrient Ratios in Nutritional Research: Expanding the Concept of Nutrient Ratios to Macronutrients
Authors: Kelly Owen J. , Gilman Jennifer C. , Ilich Jasminka Z.
Published: January 2019

We recently showed that using micronutrient ratios in nutritional research might provide more insights into how diet affects metabolism and health outcomes, based on the notion that nutrients, unlike drugs, are not consumed one at a time and do not target a single metabolic pathway. In this paper, we present a concept of macronutrient ratios, including intra- and inter-macronutrient ratios. Macronutrient intakes from food only, from the What We Eat in America website (summarized National Health and Nutrition Examination Survey data) were transposed into Microsoft Excel to generate ratios. Overall, the dietary ratios of macronutrients may be more revealing and useful in epidemiology and in basic nutritional research than focusing on individual protein, fat, and carbohydrate intakes. While macronutrient ratios may be applied to all types of nutritional research, nutritional epidemiology, and, ultimately, dietary guidelines, the methodology required has not been established yet. In the meantime, intra- and inter-macronutrient ratios may serve as a measure of individual and total macronutrient quality.
Proprietary Milk Protein Concentrate Reduces Joint Discomfort While Improving Exercise Performance in Non-Osteoarthritic Individuals
Authors: Ziegenfuss Tim , Kerksick Chad , Kedia A. , Sandrock Jennifer , Raub Betsy , Lopez Hector
Published: January 2019

Milk and dairy products are known to contain various bioactives with potential anti-inflammatory and immune modulating effects. Previous research has indicated that milk produced from hyperimmunized cows provided meaningful health benefits to individuals suffering from varying degrees of osteoarthritis and rheumatoid arthritis. PURPOSE: To examine the impact of a proprietary milk protein concentrate on joint discomfort and physical function, exercise performance, quality of life and various measures of affect. METHODS: Non-osteoarthritic men (42.5 ± 8.9 years, 176.7 ± 6.7 cm, 89.9 ± 11.5 kg, 28.8 ± 3.5 kg/m2, n = 30) and women (46.4 ± 9.6 years, 163.1 ± 8.2 cm, 72.2 ± 13.1 kg, 27.2 ± 5.3 kg/m2, n = 28) with mild to moderate knee pain during physical activity were randomized in a double-blind, placebo-controlled fashion to consume daily either a placebo (PLA) or a proprietary milk protein concentrate (MP) for a period of 8 weeks. Participants completed a functional capacity test pre and post-supplementation and completed visual analog scales (VAS), a 6-min walking test, WOMAC and profile of mood states (POMS) to assess changes in joint health, discomfort, physical function, exercise performance and affect. Mixed factorial ANOVA was used for all statistical analysis and significance was set a priori at p ≤ 0.05. RESULTS: Distance covered in the 6-min walking significantly improved 9% in MP versus 2% in PLA (mean difference: 110 ± 43 m, p = 0.012) in addition to 11 WOMAC components and 5 VAS reflective of MP improving joint health, discomfort and joint stability (all p < 0.05 vs. PLA). Additionally, MP also improved overall perceptions of neck and back health compared to PLA. Serum and whole blood indicators of clinical safety remained within normal ranges throughout the study. CONCLUSIONS: In comparison to placebo, daily doses of proprietary milk protein concentrate yielded improvements in several components of the WOMAC, multiple visual analog scales indicative of joint health and stability, discomfort and pain, as well as significant improvements in distance covered during a 6-min walking test. Supplementation was well tolerated with no significant changes in whole-blood or serum markers of clinical safety.
Effect of Cell Concentration on the Persistence in the Human Intestine of Four Probiotic Strains Administered through a Multispecies Formulation
Authors: Taverniti Valentina , Koirala Ranjan , Dalla Via Alessandro , Gargari Giorgio , Leonardis Elena , Arioli Stefania , Guglielmetti Simone
Published: January 2019

Studies devoted to evaluating the outcome of different doses of probiotics are very limited, especially for multistrain formulations. In this context, we performed an intervention study that aimed to compare the effect of the administration of two doses (7 billion and 70 billion bacterial cells) of a multistrain probiotic formulation on the persistence of the four probiotic strains that were present in the product in the fecal samples collected from healthy subjects. The overall persistence of the probiotic strains was significantly higher for the 70 billion formulation than for the 7 billion formulation. Furthermore, probiotic strains were detected earlier and for longer for the 70 billion formulation compared to those for the 7 billion formulation. All probiotic strains were recovered alive from the 70 billion preparation, whereas recovery was not possible in a few fecal samples upon administration of the 7 billion preparation. In addition, the overall number of viable probiotic cells recovered on day 14 (i.e., the last day of consumption) was significantly higher for the 70 billion formulation than that for the 7 billion formulation. Finally, we found that the viability of the probiotic cells was stable over the course of the trial independent of volunteers’ handling, demonstrating good manufacturing of the product. In conclusion, this study demonstrated that strains belonging to different taxa may coexist in the human gastrointestinal tract upon ingestion of a multispecies probiotic formulation. Moreover, this study suggests that higher doses of bacterial cells in probiotic formulations may permit a higher, earlier, and longer recovery of the probiotics in the feces of healthy adults.