bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Status of Direct Acting Antiviral Agents against Hepatitis C Virus Infection in Pakistan
Authors: Khaliq Saba , Raza Syed
Published: November 2018

In Pakistan, the burden of the hepatitis C virus (HCV) infection is the second highest in the world with the development of chronic hepatitis. Interferon-based combination therapy with ribavirin was the only available treatment until a few years back, with severe side-effects and high failure rates against different genotypes of HCV. Interferon-free all-oral direct-acting antiviral agents (DAAs) approved by the FDA have revolutionized the HCV therapeutic landscape due to their efficiency in targeting different genotypes in different categories of patients, including treatment naïve, treatment failure and relapsing patients, as well as patients with compensated and decompensated cirrhosis. The availability and use of these DAAs is limited in the developing world. Sofosbuvir (SOF), a uridine nucleotide analogue and inhibitor of HCV encoded NS5B polymerase, is now a widely available and in-use DAA in Pakistan; whereas daclatasvir was recently added in the list. According to the documented results, there is hope that this disease can be effectively cured in Pakistan, although a few concerns still remain. The aim of this article is to review the effectiveness of DAAs and the current status of this treatment against HCV genotype 3 infection in Pakistan; various factors associated with SVR; its limitations as an effective treatment regime; and future implications.
Manufacturing of High-Performance Bi-Metal Bevel Gears by Combined Deposition Welding and Forging
Authors: Chugreeva Anna , Mildebrath Maximilian , Diefenbach Julian , Barroi Alexander , Lammers Marius , Hermsdorf Jörg , Hassel Thomas , Overmeyer Ludger , Behrens Bernd-Arno
Published: November 2018

The present paper describes a new method concerning the production of hybrid bevel gears using the Tailored Forming technology. The main idea of the Tailored Forming involves the creation of bi-metal workpieces using a joining process prior to the forming step and targeted treatment of the resulting joint by thermo-mechanical processing during the subsequent forming at elevated temperatures. This improves the mechanical and geometrical properties of the joining zone. The aim is to produce components with a hybrid material system, where the high-quality and expensive material is located in highly stressed areas only. When used appropriately, it is possible to reduce costs by using fewer high-performance materials than in a component made of a single material. There is also the opportunity to significantly increase performance by combining special load-tailored high-performance materials. The core of the technology consists in the material-locking coating of semi-finished parts by means of plasma-transferred-arc welding (PTA) and subsequent forming. In the presented investigations, steel cylinders made of C22.8 are first coated with the higher-quality heat-treatable steel 41Cr4 using PTA-welding and then hot-formed in a forging process. It could be shown that the applied coating can be formed successfully by hot forging processes without suffering any damage or defects and that the previous weld structure is completely transformed into a homogeneous forming-typical structure. Thus, negative thermal influences of the welding process on the microstructure are completely neutralized.
Anisotropy of the Microstructure and Tensile Properties in Ti-5Al-5Mo-5V-1Cr-1Fe near β Titanium Alloy during Hot Rolling and Heat Treatment
Authors: Zhang Xiaoyong , Mei Yaping , Lv Yaping , Chen Chao , Zhou Kechao
Published: November 2018

Ti-55511 billet with the acicular α initial microstructure was hot rolled (HR sample) and then heat treated (HR+HT sample) at 750 °C. The effects of HR and HT on the anisotropy of microstructure, texture, and tensile properties were investigated. The tensile results show that there are obvious anisotropic tensile properties between RD and TD. The anisotropic elongation of HR sample is related to the morphology of α phase. After HR, the acicular α is parallel to RD. As for RD specimen, the transgranular propagation of microcrack passing through the acicular α phase leads to the ductile fracture, thus showing the higher ductility than TD specimen. While the intergranular propagation of microcrack passing by the equiaxed α phase in TD specimen causes the brittle fracture. The anisotropic strength of HR sample depends on the relationship among texture type of α phase, slip system, and loading direction. The maximum texture intensity at TD leads to the easy activation of basal slip system in RD and that of prismatic slip system in TD, and then causes the lower strength of RD specimen than TD specimen. After HT, the decreased anisotropy of elongation and strength can be attributed to the increased α size and the decreased texture intensity of α phase. These results demonstrate that anisotropic tensile properties mainly depend on the morphology and texture of α phase.
Trapping a Hot Drop on a Superhydrophobic Surface with Rapid Condensation or Microtexture Melting
Authors: Shiri Samira , Murrizi Armela , Bird James C.
Published: November 2018

A water drop can bounce upon impacting a superhydrophobic surface. However, on certain superhydrophobic surfaces, a water drop will stick rather than bounce if it is sufficiently hot. Here, we aim to better understand the mechanisms that can lead to this bouncing-sticking transition. Specifically, we model two potential mechanisms in which a superhydrophobic surface could trap a sufficiently hot drop within milliseconds: melting of microtextured wax and condensation of the vapor within the superhydrophobic texture. We then test these mechanisms through systematic drop impact experiments in which we independently vary the substrate and drop temperatures on a waxy superhydrophobic Nasturtium leaf. We find that, whenever the surface or the drop is above a microtexture-melting temperature, the drop sticks. Below this temperature, a critical temperature threshold for bouncing can be predicted and controlled by considering the relative timescales between condensation growth and drop residence time. We envision that these results can provide insight into the design of a new class of superhydrophobic surfaces to act as a rapid thermal fuse to prevent drops that exceed a critical temperature from bouncing onto a thermally sensitive target.
Transfer Tiling of Nanostructures for Large-Area Fabrication
Authors: Kim Jaekyoung , Yoon Hyunsik
Published: November 2018

The fabrication of nanoscale patterns over a large area has been considered important but difficult, because there are few ways to satisfy both conditions. Previously, visually tolerable tiling (VTT) for fabricating nanopatterns for optical applications has been reported as a candidate for large area fabrication. The essence of VTT is the inevitable stitching of the nanoscale optical component, which is not seen by the naked eye if the boundary is very narrow while the tiles are overlapped. However, it had been difficult to control the shape of the spread of liquid prepolymers in the previous work, and there was room for the development of tiling. Here, we propose a method for transferring various shapes of tiles, which can be defined with a shadow mask. The method of using a transparent shadow mask can provide a wide process window, because it allows the spreading of a liquid prepolymer to be more easily controlled. We optimize the coating condition of a liquid prepolymer and the ultraviolet (UV) exposure time. Using this method, we can attach tiles of various shapes without a significant visible trace in the overlapped region.
Fabrication, Experiments, and Analysis of an LBM Additive-Manufactured Flexure Parallel Mechanism
Authors: Wei Huaxian , Wang Li , Niu Xiaodong , Zhang Jian , Simeone Alessandro
Published: November 2018

Additive manufacturing technology has advantages for realizing complex monolithic structures, providing huge potential for developing advanced flexure mechanisms for precision manipulation. However, the characteristics of flexure hinges fabricated by laser beam melting (LBM) additive manufacturing (AM) are currently little known. In this paper, the fabrication and characterization of a flexure parallel mechanism through the LBM process are reported for the first time to demonstrate the development of this technique. The geometrical accuracy of the additive-manufactured flexure mechanism was evaluated by three-dimensional scanning. The stiffness characteristics of the flexure mechanism were investigated through finite element analysis and experimental tests. The effective hinge thickness was determined based on the parameters study of the flexure parallel mechanism. The presented results highlight the promising outlook of LBM flexure parts for developing novel nanomanipulation platforms, while additional attention is required for material properties and manufacturing errors.
Investigations of the Effects of Geometric Imperfections on the Nonlinear Static and Dynamic Behavior of Capacitive Micomachined Ultrasonic Transducers
Authors: Jallouli Aymen , Kacem Najib , Lardies Joseph
Published: November 2018

In order to investigate the effects of geometric imperfections on the static and dynamic behavior of capacitive micomachined ultrasonic transducers (CMUTs), the governing equations of motion of a circular microplate with initial defection have been derived using the von Kármán plate theory while taking into account the mechanical and electrostatic nonlinearities. The partial differential equations are discretized using the differential quadrature method (DQM) and the resulting coupled nonlinear ordinary differential equations (ODEs) are solved using the harmonic balance method (HBM) coupled with the asymptotic numerical method (ANM). It is shown that the initial deflection has an impact on the static behavior of the CMUT by increasing its pull-in voltage up to 45%. Moreover, the dynamic behavior is affected by the initial deflection, enabling an increase in the resonance frequencies and the bistability domain and leading to a change of the frequency response from softening to hardening. This model allows MEMS designers to predict the nonlinear behavior of imperfect CMUT and tune its bifurcation topology in order to enhance its performances in terms of bandwidth and generated acoustic power while driving the microplate up to 80% beyond its critical amplitude.
Identification of Epigenetic Mechanisms Involved in the Anti-Asthmatic Effects of Descurainia sophia Seed Extract Based on a Multi-Omics Approach
Authors: Baek Su-Jin , Chun Jin Mi , Kang Tae-Wook , Seo Yun-Soo , Kim Sung-Bae , Seong Boseok , Jang Yunji , Shin Ga-Hee , Kim Chul
Published: November 2018

Asthma, a heterogeneous disease of the airways, is common around the world, but little is known about the molecular mechanisms underlying the interactions between DNA methylation and gene expression in relation to this disease. The seeds of Descurainia sophia are traditionally used to treat coughs, asthma and edema, but their effects on asthma have not been investigated by multi-omics analysis. We undertook this study to assess the epigenetic effects of ethanol extract of D. sophia seeds (DSE) in an ovalbumin (OVA)-induced mouse model of asthma. We profiled genome-wide DNA methylation by Methyl-seq and characterized the transcriptome by RNA-seq in mouse lung tissue under three conditions: saline control, OVA-induced, and DSE-treated. In total, 1995 differentially methylated regions (DMRs) were identified in association with anti-asthmatic effects, most in promoter and coding regions. Among them, 25 DMRs were negatively correlated with the expression of the corresponding 18 genes. These genes were related to development of the lung, respiratory tube and respiratory system. Our findings provide insights into the anti-asthmatic effects of D. sophia seeds and reveal the epigenetic targets of anti-inflammatory processes in mice.
Synthesis of Novel Benzazole Derivatives and Evaluation of Their Antidepressant-Like Activities with Possible Underlying Mechanisms
Authors: Tokgöz Gamze , Demir Özkay Ümide , Osmaniye Derya , Turan Yücel Nazlı , Can Özgür Devrim , Kaplancıklı Zafer Asım
Published: November 2018

Novel benzazole derivative compounds 4a–4h were obtained by the reaction of corresponding 2-(benzazol-2-ylthio)acetohydrazide and appropriate 4-substituted benzaldehydes. The chemical structures of the synthesized compounds were elucidated by FT-IR, 1H-NMR, 13C-NMR and LCMS spectroscopic methods. Antidepressant-like effects of the compounds were evaluated by tail suspension test (TST) and modified forced swimming tests (MFST). Moreover, locomotor activities of the animals were assessed by an activity cage apparatus. In the series, compounds 4a, 4b, 4e and 4f (at 50 mg/kg) significantly decreased the immobility time of mice in both of the TST and MFST. The same compounds prolonged the swimming time of animals in MFST without any change in the climbing duration. These data indicated that compounds 4a, 4b, 4e and 4f possess significant antidepressant-like activities. Moreover, pre-treatments with p-chloro-phenylalanine methyl ester (an inhibitor of serotonin synthesis), NAN-190 (a 5-HT1A antagonist), ketanserin (a 5-HT2A/2C antagonist), and ondansetron (a 5-HT3 antagonist) reversed the exhibited pharmacological effects. Results of the mechanistic studies suggested the involvement of serotonergic system and contributions of 5-HT1A, 5-HT2A/2C and 5-HT3 receptors to the antidepressant-like effects of compounds 4a, 4b, 4e and 4f. Furthermore, unchanged locomotor activity of mice following the administrations of these four derivatives confirmed that the presented antidepressant-like effects are specific.
Interfacial Adhesion and Mechanical Properties of PET Fabric/PVC Composites Enhanced by SiO2/Tributyl Citrate Hybrid Sizing
Authors: Pu Dandan , Liu Fuyao , Dong Yubing , Ni Qingqing , Fu Yaqin
Published: November 2018

Poly(ethylene terephthalate) (PET) fabric-reinforced polyvinyl chloride (PVC) composites have a wide range of applications, but the interface bonding of PET fabric/PVC composites has remained a challenge. In this work, a new in-situ SiO2/tributyl citrate sizing agent was synthesized according to the principle of “similar compatibility.” The developed sizing agent was used as a PET surface modifier to enhance the interfacial performance of PET fabric/PVC composites. The morphology and structure of the PET filaments, the wettability and tensile properties of the PET fabric, the interfacial adhesion, and the tensile and tearing properties of the PET fabric/PVC composites were investigated. Experimental results showed that many SiO2 nanoparticles were scattered on the surface of the modified PET filaments. Moreover, the surface roughness of the modified PET filaments remarkably increased in comparison with that of the untreated PET filaments. The contact angle of the modified PET filaments was also smaller than that of the untreated ones. The peeling strength of the modified PET fabrics/PVC composites was 0.663 N/mm, which increased by 62.50% in comparison with the peeling strength of the untreated ones (0.408 N/mm). This work provides a new approach to the surface modification of PET and improves the properties of PET fabric/PVC composites.
Controlling the Amorphous and Crystalline State of Multinary Alloy Nanoparticles in An Ionic Liquid
Authors: Garzón-Manjón Alba , Meyer Hajo , Grochla Dario , Löffler Tobias , Schuhmann Wolfgang , Ludwig Alfred , Scheu Christina
Published: November 2018

Controlling the amorphous or crystalline state of multinary Cr-Mn-Fe-Co-Ni alloy nanoparticles with sizes in the range between ~1.7 nm and ~4.8 nm is achieved using three processing routes. Direct current sputtering from an alloy target in the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide leads to amorphous nanoparticles as observed by high-resolution transmission electron microscopy. Crystalline nanoparticles can be achieved in situ in a transmission electron microscope by exposure to an electron beam, ex situ by heating in vacuum, or directly during synthesis by using a high-power impulse magnetron sputtering process. Growth of the nanoparticles with respect to the amorphous particles was observed. Furthermore, the crystal structure can be manipulated by the processing conditions. For example, a body-centered cubic structure is formed during in situ electron beam crystallization while longer ex situ annealing induces a face-centered cubic structure.
Evaluation Tool Development for Food Literacy Programs
Authors: Begley Andrea , Paynter Ellen , Dhaliwal Satvinder S.
Published: November 2018

Food literacy is described as the behaviours involved in planning, purchasing, preparing, and eating food and is critical for achieving healthy dietary intakes. Food literacy programs require valid and reliable evaluation measures. The aim of this paper is to describe the development and validation of a self-administered questionnaire to measure food literacy behaviours targeted by the Food Sensations® for Adults program in Western Australia. Validity and reliability tests were applied to questionnaire item development commencing with (a) a deductive approach using Australian empirical evidence on food literacy as a construct along with its components and (b) adapting an extensively-tested food behaviour checklist to generate a pool of items for investigation. Then, an iterative process was applied to develop a specific food literacy behaviour checklist for program evaluation including exploratory factor analysis. Content, face, and construct validity resulted in a 14-item food behaviour checklist. Three factors entitled Plan & Manage, Selection, and Preparation were evident, resulting in Cronbach’s alpha 0.79, 0.76, and 0.81, respectively, indicating good reliability of each of these factors. This research has produced a validated questionnaire, is a useful starting point for other food literacy programs, and has applications globally.
Are Raw Brassica Vegetables Healthier Than Cooked Ones? A Randomized, Controlled Crossover Intervention Trial on the Health-Promoting Potential of Ethiopian Kale
Authors: Schlotz Nina , Odongo Grace A. , Herz Corinna , Waßmer Hanna , Kühn Carla , Hanschen Franziska S. , Neugart Susanne , Binder Nadine , Ngwene Benard , Schreiner Monika , Rohn Sascha , Lamy Evelyn
Published: November 2018

The present human intervention trial investigated the health-promoting potential of B. carinata, with a focus on effects of thermal processing on bioactivity. Twenty-two healthy subjects consumed a B. carinata preparation from raw (allyl isothiocyanate-containing) or cooked (no allyl isothiocyanate) leaves for five days in a randomized crossover design. Peripheral blood mononuclear cells were exposed to aflatoxin B1 (AFB1), with or without metabolic activation using human S9 mix, and subsequently analyzed for DNA damage using the comet assay. Plasma was analyzed for total antioxidant capacity and prostaglandin E2 (PGE2) levels. Cooked B. carinata significantly reduced DNA damage induced by AFB1 as compared to baseline levels (+S9 mix: 35%, −S9 mix: 33%, p ≤ 0.01, respectively). Raw B. carinata only reduced DNA damage by S9-activated AFB1 by 21% (p = 0.08). PGE2 plasma levels were significantly reduced in subjects after consuming raw B. carinata. No changes in plasma antioxidant capacity were detectable. A balanced diet, including raw and cooked Brassica vegetables, might be suited to fully exploit the health-promoting potential. These results also advocate the promotion of B. carinata cultivation in Eastern Africa as a measure to combat effects of unavoidable aflatoxin exposure.
Attenuation of Free Fatty Acid-Induced Muscle Insulin Resistance by Rosemary Extract
Authors: Vlavcheski Filip , Tsiani Evangelia
Published: November 2018

Elevated blood free fatty acids (FFAs), as seen in obesity, impair muscle insulin action leading to insulin resistance and Type 2 diabetes mellitus. Serine phosphorylation of the insulin receptor substrate (IRS) is linked to insulin resistance and a number of serine/threonine kinases including JNK, mTOR and p70 S6K have been implicated in this process. Activation of the energy sensor AMP-activated protein kinase (AMPK) increases muscle glucose uptake, and in recent years AMPK has been viewed as an important target to counteract insulin resistance. We reported recently that rosemary extract (RE) increased muscle cell glucose uptake and activated AMPK. However, the effect of RE on FFA-induced muscle insulin resistance has never been examined. In the current study, we investigated the effect of RE in palmitate-induced insulin resistant L6 myotubes. Exposure of myotubes to palmitate reduced the insulin-stimulated glucose uptake, increased serine phosphorylation of IRS-1, and decreased the insulin-stimulated phosphorylation of Akt. Importantly, exposure to RE abolished these effects and the insulin-stimulated glucose uptake was restored. Treatment with palmitate increased the phosphorylation/activation of JNK, mTOR and p70 S6K whereas RE completely abolished these effects. RE increased the phosphorylation of AMPK even in the presence of palmitate. Our data indicate that rosemary extract has the potential to counteract the palmitate-induced muscle cell insulin resistance and further studies are required to explore its antidiabetic properties.
Accuracy and Validity of Resting Energy Expenditure Predictive Equations in Middle-Aged Adults
Authors: Amaro-Gahete Francisco J. , Jurado-Fasoli Lucas , De-la-O Alejandro , Gutierrez Ángel , Castillo Manuel J. , Ruiz Jonatan R.
Published: November 2018

Indirect calorimetry (IC) is considered the reference method to determine the resting energy expenditure (REE), but its use in a clinical context is limited. Alternatively, there is a number of REE predictive equations to estimate the REE. However, it has been shown that the available REE predictive equations could either overestimate or underestimate the REE as measured by IC. Moreover, the role of the weight status in the accuracy and validity of the REE predictive equations requires further attention. Therefore, this study aimed to determine the accuracy and validity of REE predictive equations in normal-weight, overweight, and obese sedentary middle-aged adults. A total of 73 sedentary middle-aged adults (53% women, 40–65 years old) participated in the study. We measured REE by indirect calorimetry, strictly following the standard procedures, and we compared it with the values obtained from 33 predictive equations. The most accurate predictive equations in middle-aged sedentary adults were: (i) the equation of FAO/WHO/UNU in normal-weight individuals (50.0% of prediction accuracy), (ii) the equation of Livingston in overweight individuals (46.9% of prediction accuracy), and (iii) the equation of Owen in individuals with obesity (52.9% of prediction accuracy). Our study shows that the weight status plays an important role in the accuracy and validity of different REE predictive equations in middle-aged adults.
The Role of Vitamin D Oral Supplementation in Insulin Resistance in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Łagowska Karolina , Bajerska Joanna , Jamka Małgorzata
Published: November 2018

Objective: To evaluate the effect of vitamin D supplementation (alone or with co-supplementation) on insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods: We performed a literature search of databases (Medline, Scopus, Web of Knowledge, Cochrane Library) and identified all reports of randomized controlled trials (RCTs) published prior to April 2018. We compared the effects of supplementation with vitamin D alone (dose from 1000 IU/d to 60,000 IU/week) or with co-supplements to the administration of placebos in women diagnosed with PCOS. The systematic review and meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews (Prospero) as number CRD42018090572. Main results: Eleven of 345 identified studies were included in the analysis; these involved 601women diagnosed with PCOS. Vitamin D as a co-supplement was found to significantly decrease fasting glucose concentrations and the HOMA-IR value. HOMA-IR also declined significantly when vitamin D was supplemented with a dose lower than 4000 IU/d. Conclusions: Evidence from RCTs suggests that the supplementation of PCOS patients with continuous low doses of vitamin D (<4000 IU/d) or supplementation with vitamin D as a co-supplement may improve insulin sensitivity in terms of the fasting glucose concentration (supplementation with vitamin D in combination with other micronutrients) and HOMA-IR (supplementation with vitamin D in continuous low daily doses or as co-supplement).
Evaluation of Agraz Consumption on Adipocytokines, Inflammation, and Oxidative Stress Markers in Women with Metabolic Syndrome
Authors: Espinosa-Moncada Juliana , Marín-Echeverri Catalina , Galvis-Pérez Yeisson , Ciro-Gómez Gelmy , Aristizábal Juan C. , Blesso Christopher N. , Fernandez Maria Luz , Barona-Acevedo Jacqueline
Published: November 2018

Metabolic syndrome (MetS) is characterized by increased oxidative stress and a pro-inflammatory state. Vaccinium meridionale Swartz (known as “agraz”) is a berry rich in polyphenolic compounds with demonstrated antioxidant activity and anti-inflammatory effects in preclinical studies. The aim of this study was to evaluate the effects of agraz consumption on inflammatory and oxidative stress markers in women with MetS. Forty women with MetS (47 ± 9 years) were randomly assigned to consume daily either 200 mL of agraz nectar or placebo over four weeks in a double-blind, cross-over design study, separated by a 4-week washout period. Metabolic and inflammatory markers in serum and antioxidant/oxidative stress markers in serum and urine were assessed at the end of each period. Serum antioxidant capacity measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method was significantly higher (p = 0.028), while urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was lower (p = 0.041) after agraz consumption, compared to placebo. In conclusion, consumption of agraz during four weeks increased serum antioxidant capacity and decreased a marker of DNA oxidative damage in women with MetS, compared to placebo. These results suggest that agraz consumption may play a protective role in patients with MetS.
Effects of 4-Week Creatine Supplementation Combined with Complex Training on Muscle Damage and Sport Performance
Authors: Wang Chia-Chi , Fang Chu-Chun , Lee Ying-Hsian , Yang Ming-Ta , Chan Kuei-Hui
Published: November 2018

Creatine supplementation has an ergogenic effect in an acute complex training bout, but the benefits of chronic creatine supplementation during long-term complex training remain unknown. The study aimed to evaluate the effects of 4-week complex training combined with creatine supplementation on sport performances and muscle damage biomarkers. Thirty explosive athletes were assigned to the creatine or placebo group, which consumed 20 g of creatine or carboxymethyl cellulose, respectively, per day for 6 days followed by 2 g of the supplements until the end of the study. After 6 days of supplementation, subjects performed tests of one repetition maximum (1-RM) strength of half squat and complex training bouts to determine the optimal individual post-activation potentiation time. Thereafter, all subjects performed a complex training programme consisting of six sets of 5-RM half squats and plyometric jumps 3 times per week for 4 weeks. Body composition, 30-m sprint and jump performances were assessed before and after the training period. Moreover, blood creatine kinase (CK) activity was analysed at the first and the last training bout. After the training, the 1-RM strength in the creatine group was significantly greater than in the placebo group (p < 0.05). CK activity after the complex training bout in the creatine group was significantly reduced compared with the placebo group (p < 0.05). No differences were noted for other variables. This study concluded that creatine supplementation combined with complex training improved maximal muscular strength and reduced muscle damage during training.
First Insights into the Gut Microbiota of Mexican Patients with Celiac Disease and Non-Celiac Gluten Sensitivity
Authors: Garcia-Mazcorro Jose F. , Rivera-Gutierrez Xaira , Cobos-Quevedo Orestes De Jesus , Grube-Pagola Peter , Meixueiro-Daza Arturo , Hernandez-Flores Karina , Cabrera-Jorge Francisco J. , Vivanco-Cid Hector , Dowd Scot E. , Remes-Troche Jose M.
Published: November 2018

Gluten-related disorders (GRDs) are common chronic enteropathies and increasing evidence suggests an involvement of the gut microbiota. We examined the gut microbiota in Mexican people afflicted with GRDs. Ultra-high-throughput 16S marker sequencing was used to deeply describe the duodenal and fecal microbiota of patients with celiac disease (CD, n = 6), non-celiac gluten sensitivity (NCGS, n = 12), and healthy subjects (n = 12) from our local area. Additionally, we also investigated the changes in gut microbiota after four weeks on a gluten-free diet (GFD) in a subset of patients from whom paired samples were available. Despite a high inter-individual variability, significant differences in various microbial populations were identified. The linear discriminant analysis (LDA) effect size (LEfSe) method revealed that the genus Actinobacillus and the family Ruminococcaceae were higher in the duodenal and fecal microbiota of NCGS patients, respectively, while Novispirillum was higher in the duodenum of CD patients (p < 0.05, LDA score > 3.5). Interestingly, paired samples from NCGS patients showed a significant difference in duodenal Pseudomonas between the baseline period (median: 1.3%; min/max: 0.47–6.8%) and the period after four weeks on GFD (14.8%; 2.3–38.5%, p < 0.01, Wilcoxon signed-rank test). These results encourage more research on GRDs in México.
Targeting the DNA Repair Endonuclease ERCC1-XPF with Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) and Its Prodrug to Enhance Cisplatin Efficacy in Human Cancer Cells
Authors: Heyza Joshua R. , Arora Sanjeevani , Zhang Hao , Conner Kayla L. , Lei Wen , Floyd Ashley M. , Deshmukh Rahul R. , Sarver Jeffrey , Trabbic Christopher J. , Erhardt Paul , Chan Tak-Hang , Dou Q. Ping , Patrick Steve M.
Published: November 2018

The 5′-3′ structure-specific endonuclease ERCC1/XPF (Excision Repair Cross-Complementation Group 1/Xeroderma Pigmentosum group F) plays critical roles in the repair of cisplatin-induced DNA damage. As such, it has been identified as a potential pharmacological target for enhancing clinical response to platinum-based chemotherapy. The goal of this study was to follow up on our previous identification of the compound NSC143099 as a potent inhibitor of ERCC1/XPF activity by performing an in silico screen to identify structural analogues that could inhibit ERCC1/XPF activity in vitro and in vivo. Using a fluorescence-based DNA-endonuclease incision assay, we identified the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) as a potent inhibitor of ERCC1/XPF activity with an IC50 (half maximal inhibitory concentration) in the nanomolar range in biochemical assays. Using DNA repair assays and clonogenic survival assays, we show that EGCG can inhibit DNA repair and enhance cisplatin sensitivity in human cancer cells. Finally, we show that a prodrug of EGCG, Pro-EGCG (EGCG octaacetate), can enhance response to platinum-based chemotherapy in vivo. Together these data support a novel target of EGCG in cancer cells, namely ERCC1/XPF. Our studies also corroborate previous observations that EGCG enhances sensitivity to cisplatin in multiple cancer types. Thus, EGCG or its prodrug makes an ideal candidate for further pharmacological development with the goal of enhancing cisplatin response in human tumors.
Potential Prebiotic Properties of Nuts and Edible Seeds and Their Relationship to Obesity
Authors: Sugizaki Clara , Naves Maria
Published: November 2018

Obesity is a global epidemic chronic condition and is progressing at a rapid rate. This review focuses on the potential prebiotic properties of nuts and edible seeds and the plausible mechanisms that their consumption may help the prevention and the management of overweight and obesity. The literature review was performed by searching papers about the topic in MEDLINE and SCOPUS databases. The healthy attributes of nuts and edible seeds, especially dietary fibers and polyphenols contents, indicate that their mechanism of weight gain prevention may occur through interaction with the gut microbiota, by means of prebiotic effects. Among the etiological factors associated with obesity, the gut microbiota seems to play a significant role. Dysbiosis causes an imbalance in energy homeostasis that contributes to obesity. Three mechanisms are proposed in this review to explain the potential role of nut and edible seed consumption on intestinal homeostasis and body weight control: maintenance of the enteric barrier integrity, improvement of anti-inflammatory status and enhancement of butyrate synthesis. Further high-quality clinical trials should explore the interaction between oilseed consumption, microbiota, and body adiposity control, particularly investigating the microbiota metabolites and their relation to the prevention and management of obesity.
The Dietary Total-Fat Content Affects the In Vivo Circulating C15:0 and C17:0 Fatty Acid Levels Independently
Authors: Jenkins Benjamin , Aoun Manar , Feillet-Coudray Christine , Coudray Charles , Ronis Martin , Koulman Albert
Published: November 2018

Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption, with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat, representing one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating concentrations independent of their relative intake. Additionally, it is not clear how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining identical fatty acid compositions, we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a statistically significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was no significant change in the circulating C17:0 concentrations as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent of the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 concentrations is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).
Iron (II) Citrate Complex as a Food Supplement: Synthesis, Characterization and Complex Stability
Authors: Naviglio Daniele , Salvatore Maria Michela , Limatola Marianna , Langella Ciro , Faralli Stefano , Ciaravolo Martina , Andolfi Anna , Salvatore Francesco , Gallo Monica
Published: November 2018

Iron deficiency represents a widespread problem for a large part of the population, especially for women, and has received increasing attention in food/supplement research. The contraindications of the iron supplements commercially available (e.g., imbalances in the levels of other essential nutrients, low bioavailability, etc.) led us to search for a possible alternative. In the present work, a rapid and easy method to synthetize a solid iron (II) citrate complex from iron filings and citric acid was developed to serve, eventually, as a food supplement or additive. In order to state its atomic composition and purity, an assortment of analytical techniques was employed (e.g., combustion analysis, thermogravimetry, X-ray diffractometry, UV/Vis spectrophotometry, etc.). Results demonstrate that the synthesized crystalline solid corresponds to the formula FeC6H6O7∙H2O and, by consequence, contains exclusively iron (II), which is an advantage with respect to existing commercial products, because iron (II) is better absorbed than iron (III) (high bioavailability of iron).
Healthy Dietary Changes in Midlife Are Associated with Reduced Dementia Risk Later in Life
Authors: Sindi Shireen , Kåreholt Ingemar , Eskelinen Marjo , Hooshmand Babak , Lehtisalo Jenni , Soininen Hilkka , Ngandu Tiia , Kivipelto Miia
Published: November 2018

Diet is an important modifiable lifestyle factor related to dementia risk. Yet, the role of midlife dietary changes is unclear. The goal is to investigate whether midlife healthy dietary changes are associated with late-life dementia risk. Data were collected within the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) population-based cohort study (n = 2000) (mean baseline age = 56 years). Participants returned for two late-life re-examinations (mean age = 70 and 78 years). Self-reported midlife diet was measured in a sub-sample (n = 341) (mean total follow-up = 16.8 years). Changes in specific dietary components (fats, vegetables, sugar, salt) were measured in midlife. Dementia diagnoses were ascertained with detailed examinations. Analyses adjusted for potential confounders. Total midlife healthy dietary changes (improving quality of fats, increasing vegetables, decreasing sugar and salt) were associated with a reduced risk of dementia (fully adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) = 0.20–0.85). In contrast, when each factor was assessed individually, associations were not significant. This study is the first to show that beneficial midlife dietary changes are associated with a reduced dementia risk later in life. The results highlight the importance of targeting dietary patterns, where various food items may have synergistic effects.
The Role of Fiber in the Treatment of Functional Gastrointestinal Disorders in Children
Authors: Axelrod Cara Hannah , Saps Miguel
Published: November 2018

We reviewed the available evidence on the role of fiber in the treatment of Functional Constipation (FC) and Irritable Bowel Syndrome (IBS) in children. The vast majority of toddlers and preschoolers do not consume enough fiber. Two of the most common reasons for consultation to a pediatric gastroenterology practice include FC and IBS. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines state that the evidence does not support the use of fiber supplements in the treatment of FC in children, and the Rome IV criteria do not recommend an increase in fiber consumption, in children with IBS. Despite this, in general practice, it is commonly recommended that children who experience constipation and IBS to increase their fiber intake. We conducted a systematic review of the available evidence on the role of fiber in the treatment of FC and IBS in children. Thirteen full-text articles with a total of seven hundred and twenty-three pediatric participants were included in this review. Three clinical trials found positive effects of dietary fiber for the management of IBS. Nine out of ten trials found fiber to be either more effective than placebo, or just as effective as laxative treatment. Most studies on the use of fiber for the treatment of FC and IBS have shown its benefit. However, due to the heterogeneity in study design, length of treatment, outcome measures, and amount and type of fiber, we were unable to make a definitive recommendation supporting the use of fiber for the treatment of FC and IBS in children.
Fatigue as an Extra-Intestinal Manifestation of Celiac Disease: A Systematic Review
Authors: Jelsness-Jørgensen Lars-Petter , Bernklev Tomm , Lundin Knut E. A.
Published: November 2018

Celiac disease may present with a range of different symptoms, including abdominal problems in a broader sense, iron deficiency and “constant tiredness”. All of these symptoms should consequently lead the clinicians to consider celiac disease as a potential etiopathogenetic cause. Although the pathophysiology of celiac disease is well documented, the actual mechanisms for disease presentation(s) are less well understood. We here address the topic of fatigue in celiac disease. A systematic literature search identified 298 papers of which five met the criteria for full evaluation. None of the reviewed papers were of high quality and had several methodological weaknesses. We conclude that there is an unmet need to study the contributing factors and management of fatigue in celiac disease.
β-Cyclodextrin Does not Alter the Bioaccessibility and the Uptake by Caco-2 Cells of Olive By-Product Phenolic Compounds
Authors: Malapert Aurélia , Tomao Valérie , Margier Marielle , Nowicki Marion , Gleize Béatrice , Dangles Olivier , Reboul Emmanuelle
Published: November 2018

Alperujo—a two-phase olive mill waste that is composed of olive vegetation water and solid skin, pulp, and seed fragments - is a highly valuable olive by-product due to its high content in phenolic compounds. In this study, we assessed whether β-cyclodextrin (β-CD), which is used to extract and protect alpejuro phenolic compounds (hydroxytyrosol-O-glucoside, tyrosol, caffeic, and p-coumaric acids) could impact on their bioaccessibility (i.e., the percentage of molecule found in the aqueous phase of the digesta) and uptake by intestinal cells, by using an in vitro digestion model and Caco-2 TC7 cells in culture, respectively. Our results showed that β-CD did not change the bioaccessibility of the selected phenols. Hydroxytyrosol-O-glucoside and caffeic did not cross Caco-2 cell monolayers. Conversely ferulic acid, identified as the main caffeic acid intestinal metabolite, was absorbed through intestinal cell monolayers (~20%). Interestingly, β-CD moderately but significantly improved the local absorption of tyrosol and p-coumaric acid (2.3 + 1.4% and 8.5 ± 4.2%, respectively, p < 0.05), even if their final bioavailability (expressed as bioaccessibility × absorption by Caco-2 cells) was not modified (16.2 ± 0.6% vs. 16.8 ± 0.5% for tyrosol and 32.0 ± 3.2% vs. 37.2 ± 3.2% for p-coumaric acid, from pure alperujo and alperujo complexed with β-CD, respectively). Overall, our results show that β-CD is an interesting extraction and storage agent for phenolic compounds that does not alter their in vitro bioavailability.
Longitudinal Association between n-3 Long-Chain Polyunsaturated Fatty Acid Intake and Depressive Symptoms: A Population-Based Cohort Study in Japan
Authors: Horikawa Chika , Otsuka Rei , Kato Yuki , Nishita Yukiko , Tange Chikako , Rogi Tomohiro , Kawashima Hiroshi , Shibata Hiroshi , Ando Fujiko , Shimokata Hiroshi
Published: November 2018

It remains unclear whether n-3 long-chain polyunsaturated fatty acids (LCPUFA) have a preventive effect on depression in the general population. This study investigated the longitudinal association between n-3 LCPUFA intake and depressive symptoms in community-dwelling Japanese participants. The participants were aged 40–79 years at baseline in the cohort study, wherein examinations, including the assessment of depressive symptoms and nutritional status, were biennially conducted from 1997 to 2012. The subjects (n = 2335) who had a Center for Epidemiologic Studies Depression Scale (CES-D) score < 16 at the first examination and who participated in the follow-up study at least once were included in the analysis. The follow-up end point was the first onset (CES-D ≥ 16) or the last examination participation. Hazard ratios (95% CIs) for CES-D ≥ 16 were estimated using the adjusted Cox proportional hazards model. Overall, 22.1% participants showed depressive symptoms during follow-up (average; 8.1 years). Compared with the lowest tertile, the highest HR for EPA was 0.74 (0.60–0.93), and highest and middle HRs for DHA were 0.79 (0.63–0.98) and 0.80 (0.65–0.99) (P for trend = 0.009 and 0.032), respectively. Among populations with high fish consumption, higher n-3 LCPUFA intake may be associated with a low risk of depressive symptoms.
Inhibitory Effects of Helianthus tuberosus Ethanol Extract on Dermatophagoides farina body-induced Atopic Dermatitis Mouse Model and Human Keratinocytes
Authors: Kang Yun-Mi , Lee Kyou-Young , An Hyo-Jin
Published: November 2018

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex symptoms. To treat AD without adverse effects, alternative therapeutic agents are required. The tubers of Helianthus tuberosus L. (Jerusalem artichoke) have been used in folk remedies for diabetes and rheumatism. However, its effect on AD development remains unknown. Therefore, this study examined the inhibitory effect of H. tuberosus (HT) on AD skin symptoms using an NC/Nga mouse model and HaCaT keratinocytes. The effect of HT and associated molecular mechanisms were evaluated in Dermatophagoides farina body (Dfb)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes by ELISA, western blot, and histological analysis. Topical HT administration attenuated AD skin symptoms in Dfb-induced AD mice, with a significant reduction in the dermatitis score and production of inflammatory mediators. HT also decreased epidermal thickness and mast cell infiltration. Moreover, HT restored filaggrin expression and inhibited adhesion molecules in the mice. These effects were confirmed in vitro. Furthermore, HT suppressed the activation of NF-κB, Akt, and mitogen-activated protein kinase (MAPK) signaling pathways induced by TNF-α/IFN-γ. These results suggest that HT is a potential therapeutic agent or supplement for skin allergic inflammatory diseases such as AD.
Preventive Effect of Garlic Oil and Its Organosulfur Component Diallyl-Disulfide on Cigarette Smoke-Induced Airway Inflammation in Mice
Authors: Ko Je-Won , Jeong Seong-Hun , Kwon Hyung-Jun , Shin Na-Rae , Seo Yun-Soo , Kim Jong-Choon , Shin In-Sik , Kim Joong-Sun
Published: November 2018

Garlic (Allium sativum) has traditionally been used as a medicinal food and exhibits various beneficial activities, such as antitumor, antimicrobial, hypolipidemic, antiarthritic, and hypoglycemic activities. The aim of this study was to explore the preventive effect of garlic oil (GO) and its organosulfur component diallyl disulfide (DADS) on cigarette smoke (CS)-induced airway inflammation. Mice were exposed to CS daily for 1 h (equivalent to eight cigarettes per day) for two weeks, and intranasally instilled with lipopolysaccharide (LPS) on day 12 after the initiation of CS exposure. GO and DADS were administered to mice by oral gavage, both at rates of 20 and 40 mg/kg, for 1 h before CS exposure for two weeks. In the bronchoalveolar lavage fluid, GO and DADS inhibited the elevation in the counts of inflammatory cells, particularly neutrophils, which were induced in the CS and LPS (CS + LPS) group. This was accompanied by the lowered production (relative to the CS + LPS group) of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Histologically, GO and DADS inhibited the CS- and LPS-induced infiltration of inflammatory cells into lung tissues. Additionally, GO and DADS inhibited the phosphorylation of extracellular signal-regulated kinase and the expression of matrix metalloproteinase-9 in the lung tissues. Taken together, these findings indicate that GO and DADS could be a potential preventive agent in CS-induced airway inflammation.