bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting MAPKs, NF‐κB, and PI3K/AKT pathways by methyl palmitate ameliorates ethanol‐induced gastric mucosal injury in rats
Authors: Arab Hany H. , Salama Samir A. , Eid Ahmed H. , Kabel Ahmed M. , Shahin Nancy N. 
Published: May 2019

AbstractExcessive drinking of alcohol has been frequently associated with gastric injury; however, its underlying molecular mechanisms have been inadequately investigated. Methyl palmitate (MP) has demonstrated marked hepato‐, cardio‐ and pulmonary protective features; however, its effects on ethanol‐induced gastric injury have not been studied. The aim of the present study was to evaluate the potential gastroprotective activity of MP against ethanol‐evoked gastric mucosal damage in rats and associated molecular mechanisms, for example, mitogen‐activated protein kinases (MAPKs), nuclear factor κB (NF‐κB), and phosphoinositide 3 kinase/protein kinase B (PI3K/AKT) pathways. The rat stomachs were examined in terms of the inflammatory, oxidative, and apoptotic perturbations. Current data demonstrated that pretreatment with MP attenuated the gross gastric damage, scores of ulcer index, area of mucosal lesions and histopathology outcomes; actions which were similar to the reference antiulcer omeprazole. MP inhibited NF‐κB expression, its nuclear translocation, and the expression of its downstream signals, for example, tumor necrosis factor‐α and myeloperoxidase besides restoration of interleukin‐10 levels. Western blot analysis revealed that MP counteracted the disruption of MAPKs signaling via lowering p‐c‐Jun N‐terminal kinase 1/2 (p‐JNK1/2) expression and restoring the phospho‐extracellular signal‐regulated kinase 1/2 (p‐ERK1/2) levels without affecting p‐p38MAPK levels. Additionally, MP improved the antioxidant milieu via diminishing lipid peroxides and enhancing glutathione, glutathione peroxidase, total antioxidant capacity and mucosal nitric oxide. In the context of apoptosis, MP inhibited the cleavage of caspase‐3 and poly(ADP‐ribose)polymerase (PARP) and Bax protein expression with upregulating B cell lymphoma‐2 expression (Bcl‐2), thus, promoting gastric cellular survival. This was confirmed by MP activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K p110α and p‐AKT. Together, the present findings report the gastroprotective actions of MP mediated via its anti‐inflammatory, antioxidant, and antiapoptotic actions. The underlying molecular mechanisms involve, at least partly, the modulation of MAPKs, NF‐κB and PI3K/AKT transduction.
Ganoderma lucidum polysaccharide reduces melanogenesis by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL‐6/STAT3/FGF2 pathway
Authors: Jiang Ling , Huang Jinhua , Lu Jianyun , Hu Shuanghai , Pei Shiyao , Ouyang Yujie , Ding Yufang , Hu Yibo , Kang Liyang , Huang Lihua , Xiang Hong , Zeng Qing , Liu Lei , Chen Jing , Zeng Qinghai 
Published: May 2019

AbstractOur previous study found that Ganoderma lucidum polysaccharide (GLP), bioactive ingredients from Ganoderma lucidum, protected fibroblasts from photoaging. However, whether GLP can affect melanogenesis in melanocytes through regulating paracrine mediators that secreted by keratinocytes and fibroblasts is unclear. We aimed to investigate the efficacy and mechanisms of action of GLP in melanogenesis by regulating paracrine effects of keratinocytes and fibroblasts. The effect of GLP on cell viability affected by GLP was measured by the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. After an immortal keratinocyte line (HaCaT) and primary fibroblasts (FB) were treated with GLP, the supernatants of HaCaT and FB cells were collected and cocultured with an immortalized melanocyte line (PIG1). The expression levels of melanogenesis‐associated genes in PIG1 cells were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot analysis. Furthermore, FRS‐2, ERK, JNK, and p38 phosphorylation levels were measured. Then, major melanogenic paracrine mediators in HaCaT and FB cells treated with GLP were evaluated by qRT‐PCR and enzyme‐linked immunosorbent assay (ELISA). In addition, the expression of IL‐6 and STAT3 was examined in HaCaT and FB cells. GLP was not cytotoxic to HaCaT and FB cells. The supernatants of GLP‐treated HaCaT and FB cells downregulated the expression levels of MITF, TYR, TYRP1, TYRP2, RAB27A, and FSCN1 genes and inhibited the phosphorylation of FRS‐2, ERK, JNK, and p38 in PIG1 cells. GLP also decreased FGF2 secretion in HaCaT and FB cells. Moreover, GLP reduced IL‐6 expression and STAT3 phosphorylation in HaCaT and FB cells. GLP reduced melanogenesis in melanocytes by inhibiting the paracrine effects of keratinocytes and fibroblasts via IL‐6/STAT3/FGF2 pathway.
Loperamide: A Readily Available but Dangerous Opioid Substitute
Authors: White C. Michael 
Published: May 2019

AbstractThe antidiarrheal over‐the‐counter drug loperamide is increasingly being used to control opioid withdrawal or for opioid abuse. Taking many times above the normally recommended dose is dangerous with cardiovascular, respiratory, and neurological adverse events. Cytochrome P‐450 (CYP)2C8, CYP3A, and P‐glycoprotein inhibitors can increase the plasma and central nervous system concentrations and radically alter the risk profile of loperamide. Online forums suggest using over‐the‐counter metabolic enzyme blockers to enhance the effects. Public health options include switching over‐the‐counter loperamide to blister packs (the FDA‐preferred method), making loperamide only available by prescription, or moving the product behind the pharmacy counter. Although naloxone may ameliorate the neurological and respiratory adverse events, it is ineffective at reversing loperamide‐induced arrhythmias. Even magnesium might provide less efficacy in loperamide‐induced Torsade de Pointes necessitating the use of cardiac pacing and electrical cardioversion.
Feasibility study of highly accelerated phase‐sensitive inversion recovery myocardial viability imaging using simultaneous multislice and parallel imaging techniques
Authors: Zhang Zhehao , Sun Wenbo , Lan Lan , Zheng Yuan , Xu Jian , Du Yiping , Xu Haibo , Chen Qun 
Published: May 2019

BackgroundPhase‐sensitive inversion recovery (PSIR) is a powerful cardiac MRI method to assess myocardial viability, which can eliminate the background phase and preserve the sign of the desired magnetization during inversion recovery.Purpose/HypothesisTo shorten the acquisition time of myocardial viability imaging by introducing both simultaneous multislice (SMS) and parallel imaging (PI) into PSIR without additional acquisitions for calibration data.Study TypeProspective study.SubjectsA high‐resolution phantom and three vials with doped solutions matching typical postcontrast T1 and T2 values of scar, healthy myocardium, and blood; 18 patients (six with known myocardial infarction) were included in this study.Field Strength/Sequence3T/segmented fast spoiled gradient echo pulse sequence.AssessmentPhantom and in vivo experiments were performed to compare the performance of conventional PSIR, SMS accelerated PSIR (SMS‐PSIR, 2× acceleration), and SMS as well as PI accelerated PSIR (SMS + PI‐PSIR, 4× acceleration). In phantom experiments, the error maps, local signal‐to‐noise ratio (SNR), and contrast‐to‐noise ratio (CNR) were calculated. In in vivo experiments, the image quality and artifact level of each study were qualitatively graded (by three radiologists). G‐factor maps were calculated. The infarct size presented as a percentage of the left ventricle was measured (full‐width half‐maximum). Acquisition time of each study was recorded.Statistical TestOne‐way analysis of variance, Kruskal–Wallis test.ResultsIn phantom experiments, SNR and CNR were well preserved for SMS‐PSIR, while they dropped for SMS + PI‐PSIR, as expected. In 15 subjects, the overall image quality scores were not significantly different among conventional PSIR (3.70 ± 1.06), SMS‐PSIR (3.78 ± 0.99), and SMS + PI‐PSIR (3.47 ± 0.94; P = 0.20). The artifact level scores were also comparable among conventional PSIR (3.67 ± 1.04), SMS‐PSIR (3.77 ± 1.03), and SMS + PI‐PSIR (3.45 ± 1.00; P = 0.22). SMS‐PSIR achieved negligible g‐factor noise amplification (1.04 ± 0.03) and SMS + PI‐PSIR showed higher g‐factors (2.83 ± 0.48). The infarct size was consistent among conventional PSIR (22.51 ± 25.05%) and SMS‐PSIR (22.98 ± 26.19%), as well as SMS + PI‐PSIR (22.93 ± 25.68%; P = 0.98). The acquisition time of two short‐axis slices for SMS‐PSIR (17.6 ± 1.7 sec, 16 heartbeats) and SMS + PI‐PSIR (9.8 ± 1.9 sec, 8 heartbeats) was 30% and 17% of that for conventional PSIR (56.2 ± 8.5 sec, 32 heartbeats), respectively.Data ConclusionSMS can be implemented in PSIR without additional reference scan. The image quality is comparable with conventional PSIR, while the acquisition time is much shorter. The proposed method is also compatible with PI to further reduce the scan time.Level of Evidence: 2Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2019;50:1964–1972.
Label‐free cervicovaginal fluid proteome profiling reflects the cervix neoplastic transformation
Authors: Starodubtseva Natalia L. , Brzhozovskiy Alexander G. , Bugrova Anna E. , Kononikhin Alexey S. , Indeykina Maria I. , Gusakov Kiril I. , Chagovets Vitaliy V. , Nazarova Niso M. , Frankevich Vladimir E. , Sukhikh Gennady T. , Nikolaev Eugene N. 
Published: May 2019

AbstractCervicovaginal fluid (CVF) is a valuable source of clinical information about the female reproductive tract in both nonpregnant and pregnant women. The aim of this study is to specify the CVF proteome at different stages of cervix neoplastic transformation by label‐free quantitation approach based on liquid chromatography tandem mass spectrometry (LC‐MS/MS) method. The proteome composition of CVF from 40 women of reproductive age with human papillomavirus (HPV)‐associated cervix neoplastic transformation (low‐grade squamous intraepithelial lesion [LSIL], high‐grade squamous intraepithelial lesion [HSIL], and CANCER) was investigated. Hierarchical clustering and principal component analysis (PCA) of the proteomic data obtained by a label‐free quantitation approach show the distribution of the sample set between four major clusters (no intraepithelial lesion or malignancy [NILM], LSIL, HSIL and CANCER) depending on the form of cervical lesion. Multisample ANOVA with subsequent Welch's t test resulted in 117 that changed significantly across the four clinical stages, including 27 proteins significantly changed in cervical cancer. Some of them were indicated as promising biomarkers previously (ACTN4, VTN, ANXA1, CAP1, ANXA2, and MUC5B). CVF proteomic data from the discovery stage were analyzed by the partial least squares‐discriminant analysis (PLS‐DA) method to build a statistical model, allowing to differentiate severe dysplasia (HSIL and CANCER) from the mild/normal stage (NILM and LSIL), and receiver operating characteristic (ROC) area under the curve (AUC) were obtained on an independent set of 33 samples. The sensitivity of the model was 77%, and the specificity was 94%; AUC was equal to 0.87. CVF proteome proved to be reflect the stage of cervical epithelium neoplastic process.
norHarmane containing ionic liquid matrices for low molecular weight MALDI‐MS carbohydrate analysis: The perfect couple with α‐cyano‐4‐hydroxycinnamic acid
Authors: Schmidt De León Tobías , Salum María L. , Erra‐Balsells Rosa 
Published: May 2019

AbstractCinnamic acid derivatives, particularly α‐cyano‐4‐hydroxycinnamic acid (E‐α‐cyano‐4‐hydroxycinnamic acid or (E)‐2‐cyano‐3‐(4‐hydroxyphenyl)prop‐2‐enoate; CHCA), have been extensively used especially for protein and peptide analysis. Together with the introduction of ionic liquid MALDI matrix (ILM) started the study of applications of IL prepared with CHCA and a counter organic base (ie, aliphatic amines) in which CHCA moiety is the chromophore responsible of UV‐laser absorption. Despite the extensive studies of norharmane (9H‐pyrido[3,4‐b]indole; nHo) applications as matrix and its peculiar basic properties in the ground and electronic excited state, nHo containing ILM was never tested in MALDI‐MS experiments. This pyrido‐indole compound was introduced as MALDI matrix 22 years ago for different applications including low molecular weight (LMW) carbohydrates (neutral, acidic, and basic carbohydrates). These facts encouraged us to use it as a base, for the first time, for ILM preparation. As a rational design of new IL MALDI matrices, E‐α‐cyanocinnamic acid.nHo and E‐cinnamic acid.nHo were prepared and their properties as matrices studied. Their performance was compared with that of (a) the corresponding IL prepared with butylamine as basic component, (b) the corresponding crystalline E‐α‐cyanocinnamic and E‐cinnamic acid, and (c) the classical crystalline matrices (2,5‐dihydroxybenzoic acid, DHB; nHo) used in the analysis of neutral/sulfated carbohydrates. The IL DHB.nHo was tested, too. Herein, we demonstrate the outstanding performance for the IL CHCA.nHo for LMW carbohydrate in positive and negative ion mode (linear and reflectron modes). Sulfated oligosaccharides were detected in negative ion mode, and although the dissociation of sulfate groups was not completely suppressed the relative intensity (RI) of [M − Na]− peak was quite high. Additionally, to better understand the quite different performance of each IL tested as matrix, the physical and morphological properties in solid state were studied (optical image; MS image).
Comparison of High‐Hydrostatic‐Pressure Decellularized Versus Freeze‐Thawed Porcine Menisci
Authors: Watanabe Naoto , Mizuno Mitsuru , Matsuda Junpei , Nakamura Naoko , Otabe Koji , Katano Hisako , Ozeki Nobutake , Kohno Yuji , Kimura Tsuyoshi , Tsuji Kunikazu , Koga Hideyuki , Kishida Akio , Sekiya Ichiro 
Published: May 2019

ABSTRACTThe meniscus functions as a load distributor and secondary stabilizer in the knee, and the loss of the meniscus increases the risk of osteoarthritis. Freeze‐thawed menisci are used in clinical practice to replace defective menisci; however, the disadvantages of freeze‐thawed tissues include disease transmission and immune rejection. In this study, we decellularized menisci using high hydrostatic pressure (HHP) and compared the decellularized menisci with freeze‐thawed menisci. Porcine menisci were either pressurized at 1,000 MPa for 10 min and then washed with DNase solution or frozen at −80°C for 2 days and thawed. These menisci then underwent in vitro histological, biochemical, and biomechanical comparisons with native menisci. The HHP‐treated and freeze‐thawed menisci were also subcutaneously implanted in a pig, and later harvested for histological analysis. The numbers of histologically detected cells were significantly lower and the amount of biochemically detected DNA was approximately 100‐fold lower in HHP‐treated than in native and freeze‐thawed menisci. The compression strength of the HHP‐decellularized menisci was decreased after 1 and 50 cycles at 20% strain but was unchanged in the freeze‐thawed menisci. After implantation, the numbers of multinucleated giant cells were significantly lower around the HHP‐treated menisci than around the freeze‐thawed menisci. Recellularization of the HHP‐decellularized menisci was confirmed. Thus, although the HHP‐decellularized menisci were mechanically inferior to the freeze‐thawed meniscus in vitro, they were immunologically superior. Our study is the first to demonstrate the use of HHP for decellularization of the meniscus. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2466–2475, 2019
Effect of the crystal size on the infrared and Raman spectra of bio hydroxyapatite of human, bovine, and porcine bones
Authors: Londoño‐Restrepo Sandra M. , Zubieta‐Otero Luis F. , Jeronimo‐Cruz Rodrigo , Mondragon Maria Antonieta , Rodriguez‐García Mario E. 
Published: May 2019

AbstractThe optical properties of hydroxyapatites (HAps) and bio HAps have been studied using Raman and infrared (IR) spectroscopies to describe their crystalline quality. However, the size of the HAp crystals and their crystalline order effects have not been considered yet. This paper focuses on the study of the effect of the change in the crystallites size have on the width of the IR and Raman spectra for defatted and deproteinized bones as well as incinerated biogenic HAp obtained from bovine, porcine, and human bones. Bone samples were analyzed through Raman and IR spectroscopies, X‐ray diffraction (XRD), transmission electron microscopy (TEM), inductively coupled plasma (ICP), and scanning electron microscopy (SEM). The Raman and IR spectra for raw samples showed broad bands but, after calcination at 720 °C, became narrow and well defined. TEM images showed that all raw crystallites are ordered nanoplates contrary to the so far well‐established concept that biogenic HAps have low crystalline quality. XRD data confirmed that raw samples display broad peaks that correlated with the HRTEM images of ordered nanocrystals. This fact confirmed that the broad Raman and IR bands of raw clean bones come from nanocrystal plates. SEM analysis confirmed the increase in the crystal size after calcination from nanomicron to submicron dimensions due to a coalescence phenomenon. These results imply that the interpretation of Raman and IR spectra in the case of HAp nanoparticles has been erroneous. These results contribute to the design of biomaterials for tissue engineering based on biogenic HAp for bone regeneration.
Surface‐enhanced Raman spectroscopy for successful probing of itraconazole within poly(lactic‐co‐glycolic acid) nanoparticles
Authors: Ferreira Queila S. , da Silva Jaqueline R. , Silva Renata C. , Py‐Daniel Karen R. , Azevedo Ricardo B. , Morais Paulo C. , da Silva Sebastião W. 
Published: May 2019

AbstractThe present study reports on successful use of surface‐enhanced Raman spectroscopy to investigate itraconazole (ITZ) molecule loaded within poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs). SER spectra were recorded by depositing samples onto a nanostructured silver film, which was fabricated via electrolyte deposition of silver NPs onto silver substrate. Transmission electron microscopy, dynamic light scattering, zeta potential, and Fourier transform infrared spectroscopy were employed to support our analyses. While compared with normal Raman spectrum of ITZ powder, changes observed in the SER spectra of the samples comprising ITZ‐loaded PLGA‐NPs (sample ITZ@PLGA‐NPs) and ITZ mixed with PLGA‐NPs (sample ITZ+PLGA‐NPs) provided insights regarding the interaction between the ITZ molecule and both the silver film's surface and the PLGA‐NPs. We found spectral evidences that free ITZ molecule (sample ITZ+PLGA‐NPs) interacts with the silver film's surface via the nitrogen heterocyclic closest to the ITZ's phenyl rings. In this condition, it was verified that the ITZ molecules are more likely oriented parallel to the silver film's surface. Additionally, the ITZ molecule in the ITZ@PLGA‐NPs sample is not adsorbed onto the silver film's surface likely due to steric hindrance provided by the PLGA template. Nevertheless, the SER spectrum of the ITZ@PLGA‐NPs sample shows the signature of the ITZ molecule (likely via the electromagnetic mechanism) and the PLGA template (via the surface adsorption mechanism). Moreover, the SER spectrum recorded from the ITZ@PLGA‐NPs sample indicates weak interaction between the loaded ITZ and the PLGA template. We anticipate that the pioneering approach herein introduced can be successfully used to investigate a wide variety of bioactive molecules encapsulated within polymeric templates, thus providing a very promising, sensitive, and robust analytical tool not yet explored in this regard.
An evaluation model for island tourism competitiveness: Empirical study on Penghu Islands
Authors: Fu Yan‐Kai , Chen Yi‐Ju 
Published: May 2019

AbstractThe main purpose of this study is to propose a conceptual evaluation model for island tourism competitiveness, using fuzzy set theory to integrate expert opinions and provide relevant units with guidelines for resource allocation and tourism development. Three steps are involved in this study procedure. In the first step, the fuzzy Delphi method was used to summarize expert opinions and establish a hierarchical framework for island tourism competitiveness evaluations. The fuzzy analytic hierarchy process was used to perform weight comparison and rank the evaluation criteria, whereas the Kruskal–Wallis test was used in the third step to compare the differences among the industry, government, and academic sectors in terms of the various evaluation criteria. The study found out that the top 5 key criteria such as natural resources, historical culture, entertainment activities, transportation industry, and hotel industry have effectively enhanced the island tourism competitiveness. The Kruskal–Wallis test found out significant differences in the emphasis on local food, transportation industry, and tourism planning by industry, government, and academic sectors. Finally, the study presents several important research findings, discussions, and recommendations for future work.
Seasonal variability and regulation of bacterial production in a shallow eutrophic lake
Authors: Tsuchiya Kenji , Sano Tomoharu , Tomioka Noriko , Kohzu Ayato , Komatsu Kazuhiro , Shinohara Ryuichiro , Takamura Noriko , Nakagawa Megumi , Sugai Youta , Kuwahara Victor S. , Toda Tatsuki , Fukuda Hideki , Imai Akio 
Published: May 2019

ABSTRACTThe seasonal variation of bacterial production (BP) in a shallow, eutrophic Lake Kasumigaura was clarified from 2012 to 2016. During the studied period, BP fluctuated from 1.9 to 138 μg C L−1 d−1. There were no significant correlations between BP and bacterial abundance in any season, suggesting a strong top‐down regulation on BP throughout the year. On the other hand, BP was also related to bottom‐up regulation factors such as water temperature, phosphorus, and primary production (PP) annually. During winter, BP was positively correlated with chlorophyll a concentration, suggesting that autochthonous substrates were relatively important for BP. Moreover, BP was positively correlated with heterotrophic nanoflagellates, ciliates, and copepods, suggesting higher availability of substrates for BP. In summer, although there was no significant correlation between BP and PP, rainfall amount showed significant negative correlations with both BP and PP, suggesting depressed PP from relatively lower solar irradiance coupled with unfavorable weather conditions that decreased the substrate supply for bacteria. These results suggest that temporal variation of BP was regulated not by allochthonous, but by autochthonous substrates during both the highest (summer) and lowest (winter) productive seasons, even in a shallow, eutrophic lake. PP in autumn was approximately half that of spring due to lower solar irradiance, although water temperatures during both seasons were similar and nutrient concentrations during autumn were higher. On the other hand, BP in autumn was comparable with that in spring, and the bacterial carbon demand (= BP + bacterial respiration; 1.12 ± 0.79 g C m−2 d−1) was comparable to PP (1.16 ± 0.53 g C m−2 d−1), suggesting the relative importance of higher allochthonous substrates relative to other seasons.