bluuebunny/crossref_metadata_2025 huggingface dataset:
Conserved miR396b-GRF Regulation Is Involved in Abiotic Stress Responses in Pitaya (Hylocereus polyrhizus)
Authors: Li A-Li , Wen Zhuang , Yang Kun , Wen Xiao-Peng
Published: May 2019

MicroRNA396 (miR396) is a conserved microRNA family that targets growth-regulating factors (GRFs), which play significant roles in plant growth and stress responses. Available evidence justifies the idea that miR396-targeted GRFs have important functions in many plant species; however, no genome-wide analysis of the pitaya (Hylocereus polyrhizus) miR396 gene has yet been reported. Further, its biological functions remain elusive. To uncover the regulatory roles of miR396 and its targets, the hairpin sequence of pitaya miR396b and the open reading frame (ORF) of its target, HpGRF6, were isolated from pitaya. Phylogenetic analysis showed that the precursor miR396b (MIR396b) gene of plants might be clustered into three major groups, and, generally, a more recent evolutionary relationship in the intra-family has been demonstrated. The sequence analysis indicated that the binding site of hpo-miR396b in HpGRF6 is located at the conserved motif which codes the conserved “RSRKPVE” amino acid in the Trp–Arg–Cys (WRC) region. In addition, degradome sequencing analysis confirmed that four GRFs (GRF1, c56908.graph_c0; GRF4, c52862.graph_c0; GRF6, c39378.graph_c0 and GRF9, c54658.graph_c0) are hpo-miR396b targets that are regulated by specific cleavage at the binding site between the 10th and 11th nucleotides from the 5′ terminus of hpo-miR396b. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that hpo-miR396b is down-regulated when confronted with drought stress (15% polyethylene glycol, PEG), and its expression fluctuates under other abiotic stresses, i.e., low temperature (4 ± 1 °C), high temperature (42 ± 1 °C), NaCl (100 mM), and abscisic acid (ABA; 0.38 mM). Conversely, the expression of HpGRF6 showed the opposite trend to exposure to these abiotic stresses. Taken together, hpo-miR396b plays a regulatory role in the control of HpGRF6, which might influence the abiotic stress response of pitaya. This is the first documentation of this role in pitaya and improves the understanding of the molecular mechanisms underlying the tolerance to drought stress in this fruit.
Kinase Inhibitors with Antiepileptic Properties Identified with a Novel in Vitro Screening Platform
Authors: Liu Jing , Schenker Madison , Ghiasvand Shabnam , Berdichevsky Yevgeny
Published: May 2019

Kinase signaling plays an important role in acquired epilepsy, but only a small percentage of the total kinome has been investigated in this context. A major roadblock that prevents the systematic investigation of the contributions of kinase signaling networks is the slow speed of experiments designed to test the chronic effects of target inhibition in epilepsy models. We developed a novel in vitro screening platform based on microwire recordings from an organotypic hippocampal culture model of acquired epilepsy. This platform enables the direct, parallel determination of the effects of compounds on spontaneous epileptiform activity. The platform also enables repeated recordings from the same culture over two-week long experiments. We screened 45 kinase inhibitors and quantified their effects on seizure duration, the frequency of paroxysmal activity, and electrographic load. We identified several inhibitors with previously unknown antiepileptic properties. We also used kinase inhibition profile cross-referencing to identify kinases that are inhibited by seizure-suppressing compounds, but not by compounds that had no effect on seizures.
ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer
Authors: Salaroglio Iris C. , Mungo Eleonora , Gazzano Elena , Kopecka Joanna , Riganti Chiara
Published: May 2019

The extracellular signal-related kinases (ERKs) act as pleiotropic molecules in tumors, where they activate pro-survival pathways leading to cell proliferation and migration, as well as modulate apoptosis, differentiation, and senescence. Given its central role as sensor of extracellular signals, ERK transduction system is widely exploited by cancer cells subjected to environmental stresses, such as chemotherapy and anti-tumor activity of the host immune system. Aggressive tumors have a tremendous ability to adapt and survive in stressing and unfavorable conditions. The simultaneous resistance to chemotherapy and immune system responses is common, and ERK signaling plays a key role in both types of resistance. In this review, we dissect the main ERK-dependent mechanisms and feedback circuitries that simultaneously determine chemoresistance and immune-resistance/immune-escape in cancer cells. We discuss the pros and cons of targeting ERK signaling to induce chemo-immune-sensitization in refractory tumors.
Senescence Phenomena and Metabolic Alteration in Mesenchymal Stromal Cells from a Mouse Model of Rett Syndrome
Authors: Squillaro Tiziana , Alessio Nicola , Capasso Stefania , Di Bernardo Giovanni , Melone Mariarosa , Peluso Gianfranco , Galderisi Umberto
Published: May 2019

Chromatin modifiers play a crucial role in maintaining cell identity through modulation of gene expression patterns. Their deregulation can have profound effects on cell fate and functions. Among epigenetic regulators, the MECP2 protein is particularly attractive. Mutations in the Mecp2 gene are responsible for more than 90% of cases of Rett syndrome (RTT), a progressive neurodevelopmental disorder. As a chromatin modulator, MECP2 can have a key role in the government of stem cell biology. Previously, we showed that deregulated MECP2 expression triggers senescence in mesenchymal stromal cells (MSCs) from (RTT) patients. Over the last few decades, it has emerged that senescent cells show alterations in the metabolic state. Metabolic changes related to stem cell senescence are particularly detrimental, since they contribute to the exhaustion of stem cell compartments, which in turn determine the falling in tissue renewal and functionality. Herein, we dissect the role of impaired MECP2 function in triggering senescence along with other senescence-related aspects, such as metabolism, in MSCs from a mouse model of RTT. We found that MECP2 deficiencies lead to senescence and impaired mitochondrial energy production. Our results support the idea that an alteration in mitochondria metabolic functions could play an important role in the pathogenesis of RTT.
The Effects of Proteasome Inhibitors on Telomerase Activity and Regulation in Multiple Myeloma Cells
Authors: Shalem-Cohavi Naama , Beery Einat , Nordenberg Jardena , Rozovski Uri , Raanani Pia , Lahav Meir , Uziel Orit
Published: May 2019

The importance of telomerase, the enzyme that maintains telomere length, has been reported in many malignancies in general and in multiple myeloma (MM) in particular. Proteasome inhibitors are clinically used to combat effectively MM. Since the mechanism of action of proteasome inhibitors has not been fully described we sought to clarify its potential effect on telomerase activity (TA) in MM cells. Previously we showed that the first generation proteasome inhibitor bortezomib (Brt) inhibits TA in MM cells by both transcriptional and post-translational mechanisms and has a potential clinical significance. In the current study we focused around the anti- telomerase activity of the new generation of proteasome inhibitors, epoxomicin (EP) and MG-132 in order to clarify whether telomerase inhibition represents a class effect. We have exposed MM cell lines, ARP-1, CAG, RPMI 8226 and U266 to EP or MG and the following parameters were assessed: viability; TA, hTERT expression, the binding of hTERT (human telomerase reverse transcriptase) transcription factors and post-translational modifications. Epoxomicin and MG-132 differentially downregulated the proliferation and TA in all MM cell lines. The downregulation of TA and the expression of hTERT were faster in CAG than in ARP-1 cells. Epoxomicin was more potent than MG-132 and therefore further mechanistic studies were performed using this compound. The inhibition of TA was mainly transcriptionally regulated. The binding of three positive regulator transcription factors: SP1, c-Myc and NF-κB to the hTERT promoter was decreased by EP in CAG cells as well as their total cellular expression. In ARP-1 cells the SP1 and c-MYC binding and protein levels were similarly affected by EP while NF-κB was not affected. Interestingly, the transcription factor WT-1 (Wilms’ tumor-1) exhibited an increased binding to the hTERT promoter while its total cellular amount remained unchanged. Our results combined with our previous study of bortezomib define telomerase as a general target for proteasome inhibitors. The inhibitory effect of TA is exerted by several regulatory levels, transcriptional and post translational. SP1, C-Myc and NF-κB were involved in mediating these effects. A novel finding of this study is the role of WT-1 in the regulation of telomerase which appears as a negative regulator of hTERT expression. The results of this study may contribute to future development of telomerase inhibition as a therapeutic modality in MM.
Updates on Aptamer Research
Authors: Ali Mohamed H. , Elsherbiny Marwa E. , Emara Marwan
Published: May 2019

For many years, different probing techniques have mainly relied on antibodies for molecular recognition. However, with the discovery of aptamers, this has changed. The science community is currently considering using aptamers in molecular targeting studies because of the many potential advantages they have over traditional antibodies. Some of these possible advantages are their specificity, higher binding affinity, better target discrimination, minimized batch-to-batch variation, and reduced side effects. Overall, these characteristics of aptamers have attracted scholars to use them as molecular probes in place of antibodies, with some aptamer-based targeting products being now available in the market. The present review is aimed at discussing the potential of aptamers as probes in molecular biology and in super-resolution microscopy.
Multiscale Simulation of the Hydroabrasive Erosion of a Pelton Bucket: Bridging Scales to Improve the Accuracy
Authors: Leguizamón Sebastián , Jahanbakhsh Ebrahim , Alimirzazadeh Siamak , Maertens Audrey , Avellan François
Published: May 2019

Erosive wear of hydraulic machines is a common issue, which results in efficiency degradation, the enhancement of cavitation, and the need for expensive maintenance. Although numerical simulations of the erosion process could be very useful, both for understanding and predicting the process, its multiscale nature renders it very difficult to simulate. A previously validated multiscale model of erosion is presented. It consists of two coupled sub-models: On the microscale, the sediment impacts are simulated by means of comprehensive physical models; on the macroscale, the turbulent sediment transport and erosion accumulation are calculated. A multiscale simulation of the erosion of a prototype-scale Pelton bucket impacted by a sediment-laden water jet is presented. The simulation results, namely the erodent flux and the distributions of average impact angle and velocity on the bucket surface, bring insight into the erosion process. Furthermore, the results explain the obtained erosion distribution, which is in very good agreement with the experimental erosion measurements available in the literature for the same test case.
NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus
Authors: Del Coco Laura , Vergara Daniele , De Matteis Serena , Mensà Emanuela , Sabbatinelli Jacopo , Prattichizzo Francesco , Bonfigli Anna Rita , Storci Gianluca , Bravaccini Sara , Pirini Francesca , Ragusa Andrea , Casadei-Gardini Andrea , Bonafè Massimiliano , Maffia Michele , Fanizzi Francesco Paolo , Olivieri Fabiola , Giudetti Anna Maria
Published: May 2019

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naïve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort.
Characteristics of Individuals with Dry Eye Symptoms without Clinical Diagnosis: Analysis of a Web-Based Survey
Authors: Yamanishi Ryutaro , Uchino Miki , Kawashima Motoko , Uchino Yuichi , Yokoi Norihiko , Tsubota Kazuo
Published: May 2019

Currently, the available treatment for dry eye disease (DED) varies. The present study aimed to investigate the characteristics of undiagnosed DED and patient-based self-care management for DED based on a web-based survey performed for Tear’s Day in Japan; 1030 participants (301 women) responded; 155 participants (72 women) had a clinical diagnosis of DED. We defined undiagnosed DED (n = 116; 54 women) as those with DED symptoms, as evaluated by a frequently used questionnaire despite not having a clinical diagnosis. A multivariate adjusted model indicated that younger age (odds ratio (OR), 0.97 for each one-year decrease; 95% confidence interval (CI), 0.95–0.99), female sex (OR, 2.12; 95% CI, 1.28–3.50), and prolonged visual display terminal usage (OR, 1.12; 95% CI, 1.04–1.21) were risk factors for undiagnosed DED. To investigate the efficacy of self-care management for DED, a sub-analysis was conducted. The number of self-care methods used was significantly higher among women than men. For undiagnosed DED, those with less than three self-care methods had a significantly worse Dry Eye-related Quality-of-Life Score compared with those with diagnosed DED. This study revealed risk factors for undiagnosed DED; individuals with those risk factors need to be clinically assessed and should not rely solely on self-care.
Implant Fixation and Risk of Prosthetic Joint Infection Following Primary Total Hip Replacement: Meta-Analysis of Observational Cohort and Randomised Intervention Studies
Authors: Kunutsor Setor K. , Beswick Andrew D. , Whitehouse Michael R. , Blom Ashley W. , Lenguerrand Erik
Published: May 2019

Prosthetic joint infection (PJI), although uncommon, is a dreaded and devastating complication of total hip replacement (THR). Whether implant-related factors, such as the fixation method, influences the risk of PJI following THR is contentious. We conducted a systematic review and meta-analysis to evaluate the body of evidence linking fixation methods (cemented, uncemented, hybrid, or reverse hybrid) with the risk of PJI following primary THR. Observational studies and randomised controlled trials (RCTs) comparing fixation methods, and reporting PJI incidence following THR, were identified through MEDLINE, Embase, Web of Science, Cochrane Library, and reference lists of relevant studies up to 24 April 2019. Summary measures were relative risks (RRs) (95% confidence intervals, CIs). We identified 22 eligible articles (based on 11 distinct observational cohort studies comprising 2,260,428 THRs and 4 RCTs comprising 945 THRs). In pooled analyses of observational studies, all cemented fixations (plain and antibiotic combined), plain cemented fixations, hybrid fixations, and reverse hybrid fixations were each associated with an increased overall PJI risk when compared with uncemented fixations: 1.10 (95% CI: 1.04–1.17), 1.50 (95% CI: 1.27–1.77), 1.49 (95% CI: 1.36–1.64), and 1.49 (95% CI: 1.14–1.95), respectively. However, in the first six months, uncemented fixations were associated with increased PJI risk when compared to all cemented fixations. Compared to antibiotic-loaded cemented fixations, plain cemented fixations were associated with an increased PJI risk (1.52; 95% CI: 1.36–1.70). One RCT showed an increased PJI risk comparing plain cemented fixations with antibiotic-loaded cemented fixations. Uncemented and antibiotic-loaded cemented fixations remain options for the prevention of PJI in primary THR.
Development of Highly pH-Sensitive Hybrid Membranes by Simultaneous Electrospinning of Amphiphilic Nanofibers Reinforced with Graphene Oxide
Authors: Gorji Mohsen , Sadeghianmaryan Ali , Rajabinejad Hossein , Nasherolahkam Saman , Chen Xiongbiao
Published: May 2019

Nanofibrous-based pH sensors have shown promise in a wide range of industrial and medical applications due to their fast response time and good mechanical properties. In the present study, we fabricated pH-sensitive sensors of nanofibrous membranes by electrospinning polyurethane (PU)/poly 2-acrylamido-2-methylpropanesulfonic acid (PAMPS)/graphene oxide (GO) with indicator dyes. The morphology of the electrospun nanofibers was examined using scanning electron microscopy (SEM). The effect of hydrophilic polymer ratio and concentration of GO on the sensing response time was investigated. The sensitivity of the membranes was studied over a wide pH range (1–8) in solution tests, with color change measured by calculating total color difference using UV-vis spectroscopy. The membranes were also subjected to vapor tests at three different pH values (1, 4, 8). SEM results show the successful fabrication of bimodal fiber diameter distributions of PU (mean fiber diameter 519 nm) and PAMPS (mean fiber diameter 78 nm). Sensing response time decreased dramatically with increasing concentrations of PAMPS and GO. The hybrid hydrophobic/hydrophilic/GO nanofibrous membranes are capable of instantly responding to changes in solution pH as well as detecting pH changes in chemical vapor solution in as little as 7 s.
Assessing the Joint Value of Genomic-Based Diagnostic Tests and Gene Therapies
Authors: Gavan Sean P. , Lu Christine Y. , Payne Katherine
Published: May 2019

Gene therapy is an emerging type of treatment that may aim to provide a cure to individuals with a genetic mutation known to be causative of a specific disease. A diagnosis of the causative mutation must precede treatment with a in vivo gene therapy. Both achieving a genomic-based diagnosis and treatment with a gene therapy may result in substantial expenditures for health care systems. Uncertainties around the health care costs, risks, and benefits derived from diagnosis and treatment with a subsequent gene therapy suggests a need for developing an evidence base, underpinned by opportunity cost, to inform if, and how, these health technologies should be introduced into health care systems funded by finite budgets. This article discusses why current methods to evaluate health technologies (decision-analytic model-based cost-effectiveness analysis from the perspective of a health care system over a lifetime time horizon) are appropriate to quantify the costs and consequences of using genomic-based diagnostic tests and gene therapies in combination, rather than as separate interventions, within clinical practice. Evaluating the economic impact of test-and-treatment strategies will ensure that the opportunity cost of these health technologies is quantified fully for decision-makers who are responsible for allocating limited resources in health care systems.
Microstructure and Mechanical Properties of Galvanized-45 Steel/AZ91D Bimetallic Material by Liquid-Solid Compound Casting
Authors: Cheng Jun , Zhao Jian-hua , Zhang Jin-yong , Guo Yu , He Ke , Shang-guan Jing-Jing , Wen Fu-lin
Published: May 2019

A connection between hot-dip galvanized 45 steel and AZ91D was achieved by liquid-solid compound casting to achieve one material with a better mechanical performance and a light weight. The microstructure and properties of galvanized-steel/AZ91D bimetallic materials were investigated in this study. A scanning electron microscopy (SEM), an energy dispersive spectroscopy (EDS), and an X-ray diffraction (XRD) were applied to analyze the microstructure evolution and formation mechanism of the galvanized 45 steel/AZ91D interface zone which could be divided into three layers. Among three different layers, the layer close to AZ91D was composed of α-Mg and an eutectic structure (α-Mg + MgZn). The intermediate layer was comprised of an eutectic structure (α-Mg + MgZn), and the layer adjacent to 45 steel consisted of α-Mg and FeAl3. Furthermore, galvanized-45 steel/AZ91D bimetallic material had better shear strength than the bare-45 steel/AZ91D metallic material which can indicate that owing to the formation of metallurgical bonding, the adhesive strength of galvanized-steel and AZ91D was improved to 11.81 MPa. In addition, the fact that corrosion potential increased from −1.493 V to −1.143 V and corrosion current density changed from 3.015 × 10−5 A/cm2 to 1.34 × 10−7 A/cm2 implied that the corrosion resistance of galvanized-steel/AZ91D was much better than AZ91D.
Planetary Mill with Friction Wheels Transmission Aided by an Additional Degree of Freedom
Authors: Camargo Italo Leite de , Erbereli Rogério , Lovo João Fiore Parreira , Fortulan Carlos Alberto
Published: May 2019

Processing in planetary ball mills is well suited to a large number of applications because they are easy to operate and versatile, grinding faster than other mills. Research related to planetary mills are mainly about the process evaluation, and there are few studies on the mechanical design of such equipment. This paper describes the decision process in the design of an innovative planetary mill in which design for manufacture and assembly (DFMA) principles were used to provide compact equipment made of simple and standardized parts. We developed a friction wheel mechanism with an additional degree of freedom that improves transmission and facilitates assembly, reducing the need for adjustment. It can be applied to different equipment that relies on planetary motion or rotating devices. A prototype was built, and its grinding performance surpasses that of other types of traditional mill. The mean particle size of alumina powder was reduced from 4.2 µm to 0.9 µm in 60 minutes.
Impacts of Responsive Loads and Energy Storage System on Frequency Response of a Multi-Machine Power System
Authors: Saeed Uz Zaman Muhammad , Haider Raza , Bukhari Syed Basit Ali , Ashraf Hafiz Muhammad , Kim Chul-Hwan
Published: May 2019

In recent decades, the power grid’s configuration is shifting towards a smart grid where responsive loads and energy storage systems (ESS) are finding an increased role in the power system operation. In the presented work, a mathematical formulation for frequency response analysis of a multi-machine power system is developed, considering the individual and combined roles of ESS and responsive loads. The validity of the developed model is demonstrated with the help of multiple case studies, which consider the various configurations of the power system. Moreover, different combinations of capacities of generation units, ESS and responsive loads are also simulated. With the help of mathematical model and simulation results, it is demonstrated that ESS and responsive loads may improve the economy and performance of the power system even during the failure of a certain portion of generation capacity. Though the case studies consider non-reheat turbines only, the mathematical model and conclusions are equally valid for other types of turbines as well.
On a Variational Method for Stiff Differential Equations Arising from Chemistry Kinetics
Authors: Amat Sergio , Legaz María José , Ruiz-Álvarez Juan
Published: May 2019

For the approximation of stiff systems of ODEs arising from chemistry kinetics, implicit integrators emerge as good candidates. This paper proposes a variational approach for this type of systems. In addition to introducing the technique, we present its most basic properties and test its numerical performance through some experiments. The main advantage with respect to other implicit methods is that our approach has a global convergence. The other approaches need to ensure convergence of the iterative scheme used to approximate the associated nonlinear equations that appear for the implicitness. Notice that these iterative methods, for these nonlinear equations, have bounded basins of attraction.
A Study on Novel Extensions for the p-adic Gamma and p-adic Beta Functions
Authors: Duran Ugur , Acikgoz Mehmet
Published: May 2019

In this paper, we introduce the ρ , q -analog of the p-adic factorial function. By utilizing some properties of ρ , q -numbers, we obtain several new and interesting identities and formulas. We then construct the p-adic ρ , q -gamma function by means of the mentioned factorial function. We investigate several properties and relationships belonging to the foregoing gamma function, some of which are given for the case p = 2 . We also derive more representations of the p-adic ρ , q -gamma function in general case. Moreover, we consider the p-adic ρ , q -Euler constant derived from the derivation of p-adic ρ , q -gamma function at x = 1 . Furthermore, we provide a limit representation of aforementioned Euler constant based on ρ , q -numbers. Finally, we consider ρ , q -extension of the p-adic beta function via the p-adic ρ , q -gamma function and we then investigate various formulas and identities.
Activity Improvement and Vital Amino Acid Identification on the Marine-Derived Quorum Quenching Enzyme MomL by Protein Engineering
Authors: Wang Jiayi , Lin Jing , Zhang Yunhui , Zhang Jingjing , Feng Tao , Li Hui , Wang Xianghong , Sun Qingyang , Zhang Xiaohua , Wang Yan
Published: May 2019

MomL is a marine-derived quorum-quenching (QQ) lactonase which can degrade various N-acyl homoserine lactones (AHLs). Intentional modification of MomL may lead to a highly efficient QQ enzyme with broad application potential. In this study, we used a rapid and efficient method combining error-prone polymerase chain reaction (epPCR), high-throughput screening and site-directed mutagenesis to identify highly active MomL mutants. In this way, we obtained two candidate mutants, MomLI144V and MomLV149A. These two mutants exhibited enhanced activities and blocked the production of pathogenic factors of Pectobacterium carotovorum subsp. carotovorum (Pcc). Besides, seven amino acids which are vital for MomL enzyme activity were identified. Substitutions of these amino acids (E238G/K205E/L254R) in MomL led to almost complete loss of its QQ activity. We then tested the effect of MomL and its mutants on Pcc-infected Chinese cabbage. The results indicated that MomL and its mutants (MomLL254R, MomLI144V, MomLV149A) significantly decreased the pathogenicity of Pcc. This study provides an efficient method for QQ enzyme modification and gives us new clues for further investigation on the catalytic mechanism of QQ lactonase.
Impact of Maternal Diet on Human Milk Composition Among Lactating Women in Latvia
Authors: Aumeistere Līva , Ciproviča Inga , Zavadska Dace , Andersons Juris , Volkovs Viktors , Ceļmalniece Kristīne
Published: May 2019

Background and objectives: Many studies indicate that the maternal diet is an important factor affecting human milk composition. Human milk composition among lactating women in Latvia, as well as the maternal diet during lactation, has not been sufficiently studied. The aim of this research was to assess dietary habits and macronutrient intake among lactating women in Latvia and to examine the effect of diet on human milk composition. Materials and Methods: Research was conducted between November 2016 and December 2017. Mature human milk samples (n = 61) along with a 72h food diary, a food frequency questionnaire (FFQ), and a questionnaire about maternal and infant characteristics were obtained from voluntary women who were recruited via an invitation published in a social media member group for nursing mothers. Fat content in human milk was determined by LVS ISO 2446:2008, protein content was determined by LVS EN ISO 8968-1:2014, lactose was determined by ISO 22662:2007, and the fatty acid profile was analyzed using gas chromatography. Dietary data were evaluated using the Finnish food composition database Fineli, release 19 (3 March 2018). Results: Median values for fat, protein, and lactose in mature human milk were 4.40%, 1.08%, and 6.52%, respectively. Predominant fatty acids in human milk were oleic acid (C18:1 n9c), palmitic acid (C16:0), and linoleic acid (C18:2 n6c) at 34.60%, 24.00%, and 11.00% of total fatty acids, respectively. The trans elaidic acid (C18:1 n9t) level was <0.10% in all human milk samples. Significant, positive associations (p < 0.05) were found between maternal dietary intake of linoleic, α-linolenic, docosahexaenoic, total cis-monounsaturated, total cis-polyunsaturated, and total n-6 and n-3 polyunsaturated fatty acids, the ratio of n-6/n-3, and the level of these fatty acids in human milk. Total energy and carbohydrate intake among participants were lower, but total fat, saturated fat, and sugar intake were higher than recommended. Protein, linoleic acid, and α-linolenic acid intake were adequate, but docosahexaenoic acid intake was noticeably lower than recommended. Women should be supported with information regarding their nutritional needs during lactation and the possible impact of diet on human milk composition. Conclusion: Macronutrient (fat, protein, and lactose) content in human milk is not affected by maternal diet. Conversely, the human milk fatty acid profile is affected by the immediate diet consumed by the mother. Habitual dietary habits can also impact the fatty acid profile of human milk.
Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab
Authors: Basnet Sijan , Dhital Rashmi , Tharu Biswaraj
Published: May 2019

Pembrolizumab is a novel immune checkpoint inhibitor approved for use in non-small cell lung carcinoma. There have been a few cases that have associated adverse renal outcomes with pembrolizumab. We present a case of acute kidney injury in a patient on pembrolizumab who was noted to have acute tubulointerstitial nephritis on renal biopsy. Pembrolizumab was discontinued and the patient was started on long-term corticosteroids with a taper. Her renal function improved partially with treatment.
Peptide Mapping, In Silico and In Vivo Analysis of Allergenic Sorghum Profilin Peptides
Authors: Bokka Chandra Sekhar , Veeramachaneni Ganesh Kumar , Thunuguntla V. B. S. C. , Bobbillapati Janakiram , Bondili Jayakumar Singh
Published: May 2019

Background and objectives: Nearly 20–30% of the world’s population suffers from allergic rhinitis, among them 15% are progressing to asthma conditions. Sorghum bicolor profilin (Sorb PF), one of the panallergens, was identified, but the allergen specificity is not yet characterized. Materials and Methods: To map the antigenic determinants responsible for IgE binding, the present study is focused on in silico modeling, simulation of Sorb PF and docking of the Sorb PF peptides (PF1-6) against IgG and IgE, followed by in vivo evaluation of the peptides for its allergenicity in mice. Results: Peptide PF3 and PF4 displayed high docking G-scores (−9.05) against IgE only. The mice sensitized with PF3 peptide showed increased levels of IL5, IL12, TNF-alpha, and GMCSF when compared to other peptides and controls, signifying a strong, Th2-based response. Concurrently, the Th1 pathway was inhibited by low levels of cytokine IL2, IFN-γ, and IL-10 justifying the role of PF3 in allergenic IgE response. Conclusions: Based on the results of overlapping peptides PF3 and PF4, the N-terminal part of the PF3 peptide (TGQALVI) plays a crucial role in allergenic response of Sorghum profilin.
Serum Iron Levels and Copper-to-Zinc Ratio in Sickle Cell Disease
Authors: Antwi-Boasiako Charles , Dankwah Gifty , Aryee Robert , Hayfron-Benjamin Charles , Doku Alfred , N’guessan Benoit , Asiedu-Gyekye Isaac , Campbell Andrew
Published: May 2019

Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and “healthy” controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA “healthy” controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results: Serum levels of iron and copper were significantly elevated in the SCD patients, compared to their “healthy” counterparts (p < 0.001). These levels were further increased in patients with haemoglobin SS in vaso-occlusive crises (HbSS VOCs). Serum zinc levels were, however, significantly lower in the SCD patients, particularly during vaso-occlusion. The copper-to-zinc ratio was also found to be significantly higher in the SCD patients. Conclusion: Elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The significantly lower levels of zinc in the SCD patients may warrant zinc supplementation.
Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats
Authors: Abdulrazzaq Anmar M. , Badr Mujtaba , Gammoh Omar , Abu Khalil Asad A. , Ghanim Bayan Y. , Alhussainy Tawfiq M. , Qinna Nidal A.
Published: May 2019

Background and objectives: Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular damage, taking acetaminophen (APAP)-induced toxicity in rats as a model both in vivo and in vitro. Materials and Methods: Freshly cultured primary rat hepatocytes were treated with ascorbic acid, ALA, silymarin and their combination, both with and without the addition of APAP to evaluate their in vitro impact on cell proliferation and mitochondrial activity. In vivo study was performed on rats supplemented with the test compounds or their combination for one week followed by two toxic doses of APAP. Results: Selected liver function tests and oxidative stress markers including superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized glutathione (GSSG) were detected. The in vivo results showed that all three pretreatment compounds and their combination prevented elevation of SOD and GSSG serum levels indicating a diminished burden of oxidative stress. Moreover, ascorbic acid, ALA and silymarin in combination reduced serum levels of liver enzymes; however, silymarin markedly maintained levels of all parameters to normal ranges. Silymarin either alone or combined with ascorbic acid and ALA protected cultured rat hepatocytes and increased cellular metabolic activity. The subjected agents were capable of significantly inhibiting the presence of oxidative stress induced by APAP toxicity and the best result for protection was seen with the use of silymarin. Conclusions: The measured liver function tests may suggest an augmented hepatoprotection of the combination preparation than when compared individually.
Experimental and Computational Studies to Characterize and Evaluate the Therapeutic Effect of Albizia lebbeck (L.) Seeds in Alzheimer’s Disease
Authors: Saleem Uzma , Raza Zohaib , Anwar Fareeha , Ahmad Bashir , Hira Sundas , Ali Tahir
Published: May 2019

Background and Objectives: Alzheimer’s disease (AD) is a neurodegenerative disorder that deteriorates daily life due to loss of memory and cognitive impairment. It is believed that oxidative stress and cholinergic deficit are the leading causes of AD. Disease-modifying therapies for the treatment of AD are a challenging task for this century. The search for natural and synthetic agents has attracted the attention of researchers. The objective of this study was a scientific approach to search for most suitable remedy for AD by exploiting the potential of Albizia lebbeck (L.) seeds. Materials and Methods: Hydromethanolic extract of Albizia lebbeck seeds (ALE) was prepared by maceration. The plant was characterized by physico-chemical, phyto-chemical, and high-performance liquid chromatography (HPLC). Thirty-six Wistar albino rats were used in this study and divided into six groups (n = 6). Group I: normal control; Group II: disease control (AlCl3; 100 mg/kg); Group III: standard control (galantamine; 0.5 mg/kg); Groups IV–VI were treated ALE at 100, 200 and 300 mg/kg dose levels, respectively. All the treatments were given orally for 21 consecutive days. Y-maze, T-maze, Morris water maze, hole board, and open field behavioral tests were performed to analyze the cognitive impairment. Biochemical, histological, and computational studies were performed to support the results of behavioral tests. Results: HPLC analysis indicated the presence of quercetin, gallic acid, m-coumaric acid, and sinapic acid. ALE significantly improved the memory and cognitive impairments. Endogenous antioxidant stress biomarker levels and histopathological outcomes supported the therapeutic potential of A. lebbeck in AD. Cholinergic deficits were also ameliorated by ALE co-administration, possibly by the inhibition of hyperactive acetylcholinesterase (AChE). Docking studies supported the potential of ALE against AD. Conclusions: The data suggested that ALE has neuroprotective potential that can be exploited for beneficial effects to treat AD.
Cyriax Friction Massage—Suggestions for Improvements
Authors: Pitsillides Alexios , Stasinopoulos Dimitrios
Published: May 2019

Background and objectives: Cyriax friction massage is a widely known and used technique in the field of chronic pain management. Despite its frequent use in daily clinical practice, the technique lacks evidence to support its therapeutic value. While this might be due to various factors, the authors of this paper suggest that the technique might need to be improved and/or modernized according to the recent literature. The purpose of this letter is to further analyze our point of view. Materials and Methods: Using the most relevant methods to the subject literature, the authors intended to point out a few technical details that might need reconsideration and/or modernization. Results: An appropriate terminology is suggested in the text. Further, suggestions are made regarding the technique’s interval time, a possible addition of self-treatment, a discussion of the combination with Mill’s manipulation, tendon positioning and other parameters. Conclusions: As a therapeutic value has not yet been clearly documented, and since the modernization and/or improvement of the technique might be needed, we suggest that this technique should not be used as a first-line treatment for the management of chronic pain.
Effects of WC Particle Types on the Microstructures and Properties of WC-Reinforced Ni60 Composite Coatings Produced by Laser Cladding
Authors: Zhang Pengxian , Pang Yibin , Yu Mingwei
Published: May 2019

WC-reinforced Ni60 composite coatings with different types of WC particles were prepared on 304 stainless steel surface by laser cladding. The influences of spherical WC, shaped WC, and flocculent WC on the microstructures and properties of composite coatings were investigated. The results showed that three types of WC particles distribute differently in the cladding coatings, with spherical WC particles stacking at the bottom, shaped WC aggregating at middle and lower parts, with flocculent WC particles dispersing homogeneously. The hardnesses, wear resistances, corrosion resistances, and thermal shock resistances of the coatings are significantly improved compared with the stainless steel substrate, regardless of the type of WC that is added, and especially with regard to the microhardness of the cladding coating; the addition of spherical or shaped WC particles can be up to 2000 HV0.05 in some areas. Flocculent WC, shaped WC, and spherical WC demonstrate large to small improvements in that order. From the results mentioned above, the addition of flocculent WC can produce a cladding coating with a uniform distribution of WC that is of higher quality compared with those from spherical WC and shaped WC.
Effect of Pre-Stretching on Microstructures and Mechanical Behaviors of Creep-Aged 7055 Al Alloy and Its Constitutive Modeling
Authors: Zuo Duquan , Cao Zengqiang , Cao Yuejie , Zheng Guo
Published: May 2019

The rational pre-stretching can contribute to obtaining better mechanical properties. This paper studies the effect of creep stain, mechanical properties, and microstructures of 7055 alloy under different pre-stretching conditions. The results show that compared with solid-quenched alloy, the 7055-T6 alloy is the optimal scheme to attain more creep strain, and the range of pre-stretching from 1.6% to 3.3% is suitable for creep-aged 7055-T6 alloy to obtain better mechanical properties. Further examination by TEM test shows that pre-stretching promotes the formation of dislocations, which provides superior nucleation regions for ή phase resulting in a higher strength alloy. Meanwhile, a unified creep-aging constitutive model for 7055-T6 alloy is established which can be used to accurately predict its creep behavior under the different pre-stretching.
Fretting-Fatigue Analysis of Shot-Peened Al 7075-T651 Test Specimens
Authors: Martín Vicente , Vázquez Jesús , Navarro Carlos , Domínguez Jaime
Published: May 2019

Shot peening is a mechanical treatment that induces several changes in the material: surface roughness, increased hardness close to the surface, and, the most important, compressive residual stresses. This paper analyzes the effect of this treatment on alloy Al 7075-T651 in the case of fretting fatigue with cylindrical contact through the results of 114 fretting fatigue tests. There are three independent loads applied in this type of test: a constant normal load N, pressing the contact pad against the specimen; a cyclic bulk stress σ in the specimen; and a cyclic tangential load Q through the contact. Four specimens at each of 23 different combinations of these three parameters were tested—two specimens without any treatment and two treated with shot peening. The fatigue lives, contact surface, fracture surface, and residual stresses and hardness were studied. Improvement in fatigue life ranged from 3 to 22, depending on fatigue life. The relaxation of residual-stress distribution related to the number of applied cycles was also measured. Finally, another group of specimens treated with shot peening was polished and tested, obtaining similar lives as in the tests with specimens that were shot-peened but not polished.
Optimization and Validation of Sound Absorption Performance of 10-Layer Gradient Compressed Porous Metal
Authors: Yang Fei , Shen Xinmin , Bai Panfeng , Zhang Xiaonan , Li Zhizhong , Yin Qin
Published: May 2019

Sound absorption performance of a porous metal can be improved by compression and optimal permutation, which is favorable to promote its application in noise reduction. The 10-layer gradient compressed porous metal was proposed to obtain optimal sound absorption performance. A theoretical model of the sound absorption coefficient of the multilayer gradient compressed porous metal was constructed according to the Johnson-Champoux-Allard model. Optimal parameters for the best sound absorption performance of the 10-layer gradient compressed porous metal were achieved by a cuckoo search algorithm with the varied constraint conditions. Preliminary verification of the optimal sound absorber was conducted by the finite element simulation, and further experimental validation was obtained through the standing wave tube measurement. Consistencies among the theoretical data, the simulation data, and the experimental data proved accuracies of the theoretical sound absorption model, the cuckoo search optimization algorithm, and the finite element simulation method. For the investigated frequency ranges of 100–1000 Hz, 100–2000 Hz, 100–4000 Hz, and 100–6000 Hz, actual average sound absorption coefficients of optimal 10-layer gradient compressed porous metal were 0.3325, 0.5412, 0.7461, and 0.7617, respectively, which exhibited the larger sound absorption coefficients relative to those of the original porous metals and uniform 10-layer compressed porous metal with the same thickness of 20 mm.
Pantoea spp. Associated with Smooth Crabgrass (Digitaria ischaemum) Seed Inhibit Competitor Plant Species
Authors: Elmore Matthew T. , White James F. , Kingsley Kathryn L. , Diehl Katherine H. , Verma Satish K.
Published: May 2019

Digitaria ischaemum (Schreb.) Schreb. ex Muhl. and Poa annua L. are competitive, early successional species which are usually considered weeds in agricultural and turfgrass systems. Bacteria and fungi associated with D. ischaemum and P. annua seed may contribute to their competitiveness by antagonizing competitor forbs, and were studied in axenic culture. Pantoea spp. were the most common bacterial isolate of D. ischaemum seed, while Epicoccum and Curvularia spp. were common fungal isolates. A variety of species were collected from non-surface sterilized P. annua. Certain Pantoea spp. isolates were antagonistic to competitor forbs Taraxacum officinale, Trifolium repens. All bacterial isolates that affected T. officinale mortality were isolated from D. ischaemum seed while none of the P. annua isolates affected mortality. Two selected bacterial isolates identified as Pantoea ananatis were evaluated further on D. ischaemum, T. repens (a competitor forb) and P. annua (a competitor grass) alone and in combination with a Curvularia sp. fungus. These bacteria alone caused >65% T. repens seedling mortality but did not affect P. annua seedling mortality. These experiments demonstrate that Pantoea ananatis associated with D. ischaemum seeds is antagonistic to competitor forbs in axenic culture. The weedy character of D. ischaemum could at least in part stem from the possession of bacteria that are antagonistic to competitor species.