bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentially critical roles of TNPO1, RAP1B, ZDHHC17, and PPM1B in the progression of coronary atherosclerosis through microarray data analysis
Authors: Zhang Xiaohui , Sun Renhua , Liu Liping 
Published: September 2018

AbstractObjectiveThis study aimed to identify more potentially critical genes associated with atherosclerotic coronary artery disease (CAD).Materials and MethodsGene expression profile of GSE12288 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened in atherosclerotic CAD samples compared with controls, followed by weighed gene coexpression network analysis (WGCNA) by which the most significant module was identified. Gene coexpression network was constructed based on genes in the most significant module, and functional annotation was also performed. In addition, microRNAs (miRNAs) that were directly associated with CAD were screened from the literature, and the miRNA‐target regulatory network was constructed based on genes in the most significant module, followed by Gene Ontology (GO) and pathway enrichment analysis. Furthermore, we used another data set of GSE42148 from the GEO database to perform data validation.ResultsWGCNA analysis showed that the turquoise module may have the most important role in atherosclerotic CAD. Genes in this module were involved in translational elongation and intracellular signal transduction. Besides, we identified five confirmed CAD‐related miRNAs. TNPO1, RAP1B, and ZDHHC17 could be targeted by four of these miRNAs. Genes such as PPM1B could be regulated by three miRNAs. Moreover, TNPO1 and ZDHHC17 were involved in the GO terms associated with protein localization and transport and the immune system; RAP1B and PPM1B were linked with intracellular signal transduction‐related pathways. In addition, PPM1B and ZDHHC17 had accordantly significant expression changes in another data set GSE42148.ConclusionTNPO1, RAP1B, ZDHHC17, and PPM1B may play essential roles in the progression of coronary atherosclerosis.
Intestinal barrier tightening by a cell‐penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis
Authors: Thomas Sunil , Hoxha Kevther , Alexander Walker , Gilligan John , Dilbarova Rima , Whittaker Kelly , Kossenkov Andrew , Prendergast George C. , Mullin James M. 
Published: September 2018

AbstractPatients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell‐penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lower 14C‐mannitol leakage across the cecal mucosa, consistent with a direct strengthening of colonic barrier function. Transcriptomic analyses of colitis tissues highlighted altered expression of genes involved in circadian rhythm, lipid metabolism, and inflammation, with a correction of the alterations by Bin1 mAb treatment to patterns characteristic of normal tissues. Overall, our results suggest that Bin1 mAb protects against UC by directly improving colonic epithelial barrier function to limit gene expression and cytokine programs associated with colonic inflammation.
In utero exposure to PM2.5 during gestation caused adult cardiac hypertrophy through histone acetylation modification
Authors: Wu Xiaoqi , Pan Bo , Liu Lingjuan , Zhao Weian , Zhu Jing , Huang Xupei , Tian Jie 
Published: September 2018

AbstractAmbient particles with a diameter of <2.5 μm (PM2.5) is a global health concern, and exposure to PM2.5 contributes to the progression of cardiovascular morbidity and mortality. In this study, pregnant c57 mice were exposed to PM2.5 during the whole gestation (approximately 300 µg/m
3 PM2.5 for 2 hours/d). A significantly low birth weight was found after in utero PM2.5 exposure, and low body weight continued for 12 weeks after birth. In the offspring, remarkable destructions of cardiac ultrastructures were determined both in newborn and adult hearts. In adulthood, hearts of mice in the PM2.5 exposed group showed cardiac hypertrophy. Protein levels of p300, CBP (histone acetyltransferase), and acetylated histone3 lysine 9 (H3K9ac) increased in the trial group; messenger RNA (mRNA) levels of GATA binding protein 4 (GATA4) and myocyte enhancer factor 2C (Mef2c) (prohypertrophic transcription factors), and mRNA levels of the classic hypertrophic genes, such as α‐MHC and β‐MHC, increased significantly in the hearts of the PM2.5 exposed group. H3K9ac levels near the promoter region of GATA4 and Mef2c went up in the PM2.5 group. The binding affinities of p300/CBP with promoters of GATA4 and Mef2c increased notably. Taken together, out data indicated that maternal exposure to PM2.5 during gestation may cause a series of cardiovascular events in the offspring; histone acetylation modification may play an important role in the programming of cardiac hypertrophy.
Novel leptin receptor signaling mutants identify location and sex‐dependent modulation of bone density, adiposity, and growth
Authors: McCabe Ian C. , Fedorko Alyssa , Myers Martin G. , Leinninger Gina , Scheller Erica , McCabe Laura R. 
Published: September 2018

AbstractLeptin, a hormone primarily produced by adipocytes, contributes to the regulation of bone health by modulating bone density, growth and adiposity. Upon leptin binding, multiple sites of the long form of the leptin receptor (LepRb) are phosphorylated to trigger activation of downstream signaling pathways. To address the role of LepRb‐signaling pathways in bone health, we compared the effects of three LepRb mutations on bone density, adiposity, and growth in male and female mice. The ∆65 mutation, which lacks the known tyrosine phosphorylation sites, caused obesity and the most dramatic bone phenotype marked by excessive bone adiposity, osteoporosis, and decreased growth, consistent with the phenotype of db/db and ob/ob mice that fully lack leptin receptor signaling. Mutation of LepRb Tyr
1138, which results in an inability to recruit and phosphorylate signal transducer and activator of transcription 3, also caused obesity, but bone loss and adiposity were more dominant in male mice and no growth defect was observed. In contrast, mutation of LepRb Tyr
985, which blocks SHP2/SOCS3 recruitment to LepRb and contributes to leptin hypersensitivity, promoted increased femur bone density only in male mice, while marrow adiposity and bone growth were not affected. Additional analyses of vertebral trabecular bone volume indicate that only the Tyr
1138 mutant mice exhibit bone loss in vertebrae. Together, our findings suggest that the phosphorylation status of specific sites of the LepRb contribute to the sex‐ and location‐dependent bone responses to leptin. Unraveling the mechanisms by which leptin responses are sex‐ and location‐dependent can contribute to the development of uniquely targeted osteoporosis therapies.
Thymoquinone protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis
Authors: Hu Xin , Liang Yuanyuan , Zhao Bo , Wang Yongyi 
Published: September 2018

AbstractOxidative stress in retinal pigment epithelium (RPE) cells may contribute to the progression of age‐related macular degeneration. Thymoquinone (TQ), an active component derived from Nigella sativa, possesses antioxidative effect. However, the role of TQ in RPE cells under oxidative stress condition remains unclear. The present study aimed to examine the protective effect of TQ against hydrogen peroxide (H2O2)‐induced oxidative stress in human RPE cells. Our results showed that TQ improved the cell viability and apoptosis in H2O2‐induced ARPE cells. We also found that the levels of reactive oxygen species and malondialdehyde induced by H2O2 were reduced after the pretreatment of TQ. In addition, the inhibitory effect of H2O2 on the glutathione (GSH) level and superoxide dismutase activity was markedly attenuated by TQ pretreatment. Moreover, TQ enhanced the activation of Nrf2/heme oxygenase 1 (HO‐1) signaling pathway in H2O2‐induced ARPE cells. Knockdown of Nrf2 abolished the protective effect of TQ on H2O2‐induced oxidative damage. These results suggested that TQ protected ARPE cells from H2O2‐induced oxidative stress and apoptosis via the Nrf2/HO‐1 signaling pathway.
The molecular mechanisms of curcumin’s inhibitory effects on cancer stem cells
Authors: Zendehdel Elham , Abdollahi Elham , Momtazi‐Borojeni Amir Abbas , Korani Mitra , Alavizadeh Seyedeh Hoda , Sahebkar Amirhossein 
Published: September 2018

AbstractCurcumin is a dietary polyphenol and a bioactive phytochemical that possesses anti‐inflammatory, antioxidant, anticancer, and chemopreventive properties, which make it capable of affecting multiple sites along the stem cell pathways to induce apoptosis in these cells. Curcumin’s function is through suppression of cytokine release, especially the secretion of interleukins. Some of the predominant activities of stem cells include regeneration of identical cells and the ability to maintain the proliferation and multipotentiality. However, these cells could be stimulated to differentiate into specific cell types, leading to the development of tumors. Cancer stem cells (CSC) are capable of sustaining tumor formation and differentiation, and are normally characterized by self‐renewal mechanisms. Furthermore, these cells might be responsible for tumor relapse and resistance to therapy. Several studies have focused on the mechanisms of curcumin action in manipulating transcription factors, signaling pathways, CSC markers, microRNAs related to CSCs functions and apoptosis induction in various human cancer cells. In the present review, we aimed to summarize the reported molecular mechanisms of curcumin’s effects on CSCs.
Identification of potential mechanism and hub genes for neuropathic pain by expression‐based genome‐wide association study
Authors: Gu Yu , Qiu Zhuolin , Cheng Nan , Chen Chaojin , Hei Ziqing , Li Xiang 
Published: September 2018

AbstractNeuropathic pain (NP) is a common pathological pain state with limited effective treatments. This study was designed to identify potential mechanisms and candidate genes using gene expression–based genome‐wide association study (eGWAS). All NP‐related microarray experiments were obtained from Gene Expression Omnibus and ArrayExpress. Significantly dysregulated genes were identified between experimental and untreated groups, and the number of microarray experiments in which each gene was dysregulated was calculated. Significantly dysregulated genes were ranked according to P values of the chi‐square test. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database, we performed functional and pathway enrichment analysis. Protein‐protein interaction (PPI) network and module analysis was performed using Cytoscape software. A total of 115 candidate genes were identified from 19 independent microarray experiments by eGWAS based on the Bonferroni threshold (
P < 2.97 × 10
−6). Immune and inflammatory responses, and complement and coagulation cascades, were respectively the most enriched biological process and pathways for candidate genes. The hub genes with highest connectivity in PPI network and two modules Ccl2 and Jun, and Ctss application of the eGWAS methodology can identify mechanisms and candidate genes associated with NP. Our results support the validity and prevalence of inflammatory and immune mechanisms across different NP models, and Ccl2, Jun, and Ctss may be the hub genes for NP.
Role of thrombin in the pathogenesis of atherosclerosis
Authors: Jaberi Najmeh , Soleimani Atena , Pashirzad Mehran , Abdeahad Hosein , Mohammadi Fariba , Khoshakhlagh Mahdieh , Khazaei Majid , Ferns Gordon A , Avan Amir , Hassanian Seyed Mahdi 
Published: September 2018

AbstractAtherosclerosis is an arterial disease associated with inflammation. Thrombin is a procoagulant and proinflammatory serine protease that contributes to the pathology of atherosclerosis by enhancing the expression of cell adhesion molecules, inducing the secretion of proinflammatory cytokines, activating inflammatory responses in atherosclerotic plaques, stimulating proliferation of aortic smooth muscle cells, and exacerbating vascular lesions at sites of injury. Hence, thrombin appears to be an important target for treatment of atherosclerosis and thrombin pharmacological inhibitors have significant therapeutic potency for suppressing inflammatory responses in cardiovascular diseases. This review summarizes the proinflammatory signaling functions of thrombin as well as the therapeutic potency of thrombin inhibitors in the pathogenesis of atherosclerosis and hence their potential therapeutic value in this condition.
Novel finding of caveolin‐2 in apical membranes of proximal tubule and first detection of caveolin‐2 in urine: A promising biomarker of renal disease
Authors: Bulacio Romina Paula , Nosetto Evangelina Cecilia , Brandoni Anabel , Torres Adriana Mónica 
Published: September 2018

AbstractCaveolin‐2 (Cav‐2) is expressed in a variety of cell tissue, and it has also been found in renal tissue. The expression of Cav‐2 in proximal tubules is still unclear. The aim of this study was to carry out a complete evaluation of the expression pattern of Cav‐2 in rat renal cortex to clarify and deepen the knowledge about the localization of Cav‐2 in the proximal tubules and also to evaluate its presence in urine. Male Wistar rats were used to assess Cav‐2 expression by Western blot analysis in homogenates, apical, and basolateral membranes from kidney cortex, in lysates and total plasma membranes from renal cortical cell suspensions, in urine, and in urinary exosomes. Cav‐2 was clearly expressed in renal cortex homogenates and in both apical and basolateral membranes isolated from kidney cortex, with a greater expression on the former membranes. It was also observed in lysates and in plasma membranes from cortical cell suspensions. Moreover, Cav‐2 was found in urine and in its exosomal fraction. These results confirmed the presence of Cav‐2 in proximal tubule cells in the kidney of healthy rats, and showed for the first time its expression at the apical membrane of these cells and in urine. Besides, urinary exosomal pathway could be involved in Cav‐2 urinary excretion under normal conditions. We observed an increase in the urinary abundance of Cav‐2 in two models of acute kidney injury, and thus we proposed the urinary excretion of Cav‐2 as a potential biomarker of kidney injury.
Roles for Kisspeptin in proliferation and differentiation of spermatogonial cells isolated from mice offspring when the cells are cocultured with somatic cells
Authors: Toolee Heidar , Rastegar Tayebeh , Solhjoo Somayeh , Mortezaee Keywan , Mohammadipour Mahshid , Kashani Iraj Regerdi , Akbari Mohammad 
Published: September 2018

AbstractKisspeptin (Kp) expression in testis has caused most of the recent research surveying its functional role in this organ. This peptide influences spermatogenesis and sperm capacitation, so it is considered as a regulator of reproduction. Kp roles exert through hypothalamic/pituitary/gonadal axis. We aimed to evaluate direct roles for Kp on proliferation and differentiation of spermatogonial cells (SCs) when the cells are cocultured with somatic cells. Somatic cells and SCs were isolated from adult azoospermic and newborn mice and then enriched using a differential attachment technique. After the evaluation of identity and colonization for SCs, the cells were cocultured with somatic cells, and three doses of Kp (10−8‐10−6 M) was assessed on proliferation (through evaluation of MVH and ID4 markers) and differentiation (via evaluation of c‐Kit and SCP3, TP1, TP2, and, Prm1 markers) of the coculture system. Investigations were continued for four succeeding weeks. At the end of each level of testosterone in the culture media was also evaluated. We found positive influence from Kp on proliferative and differentiative markers in SCs cocultured with somatic cells. These effects were dose‐dependent. There was no effect for Kp on testosterone level. From our findings, we simply conclude that Kp as a neuropeptide for influencing central part of reproductive axis could also positively affect peripheral processes related to spermatogenesis without having an effect on steroidogenesis.
Poor performance of psoas muscle index for identification of patients with higher waitlist mortality risk in cirrhosis
Authors: Ebadi Maryam , Wang Connie W. , Lai Jennifer C. , Dasarathy Srinivasan , Kappus Matthew R. , Dunn Michael A. , Carey Elizabeth J. , Montano‐Loza Aldo J. ,   From the Fitness, Life Enhancement, and Exercise in Liver Transplantation (FLEXIT) Consortium
Published: September 2018

AbstractBackgroundSarcopenia, characterized by low muscle mass, associates with mortality in patients with cirrhosis. Skeletal muscle area in a single computed tomography image at the level of the third lumbar vertebrate (L3) is a valid representative of whole body muscle mass. Controversy remains regarding applicability of psoas muscle to identify patients at greater risk of mortality. We aimed to determine psoas muscle index (PMI) association with skeletal muscle index (SMI) and to evaluate the capacity of PMI to predict liver transplant waitlist mortality.MethodsWe evaluated listed adult patients with cirrhosis from 2012 to 2013 at four North American liver transplant centres. From L3 computed tomography images within 3 months of listing, we determined SMI and PMI expressed by cm2/m2. Low SMI was defined as SMI <39 cm2/m2 in women and <50 cm2/m2 in men as published by us earlier. Cut‐offs for PMI to predict mortality were established using a receiver‐operating characteristic analysis. Mortality predictors were determined using competing‐risk analysis with reported results as subdistribution hazard ratios (sHRs).ResultsOf 353 waitlist candidates, 68% were men, mean age 56 ± 9 years, and Model for End‐stage Liver Disease of 16 ± 8 points. Low SMI was present more frequently in men than women (51 vs. 36%, P = 0.02). Moderately strong correlation between SMI and PMI was observed (r > 0.7, P < 0.001). Low PMI (males < 5.1 cm2/m2; females < 4.3 cm2/m2) yielded poor and moderate concordance with low SMI in men and women, respectively (Kappa coefficient 0.31 and 0.63). SMI (39 ± 9 vs. 43 ± 7 cm2/m2; P = 0.009) and PMI (4.4 ± 1.3 vs. 5.2 ± 1.1 cm2/m2; P = 0.001) were lower in women who died and/or were delisted (compared with non‐deceased patients) whereas men who died and/or were delisted had only lower SMI (47 ± 7 vs. 51 ± 9 cm2/m2; P = 0.003), but not PMI compared with non‐deceased patients. In women, both SMI (sHR 0.94, P = 0.048) and PMI (sHR 0.58, P = 0.002) were predictors of mortality, while in men, SMI was significant (sHR 0.95, P = 0.001) and PMI showed a trend to be (sHR 0.85, P = 0.09) associated with mortality. Overall, 104 patients (29%) were misclassified between SMI and PMI categories. Using PMI cut‐offs, 66% and 28% of low SMI men and women, who have a higher risk of mortality, were incorrectly classified as low risk.ConclusionsSkeletal muscle index is a more complete and robust measurement than PMI, especially in men with cirrhosis. Low PMI identifies an incomplete subset of patients at increased risk of mortality indicated by low SMI. Given the poor performance of PMI, SMI should not be substituted by PMI.
Relationship Between Time of Class and Student Grades in an Active Learning Course
Authors: Marbouti Farshid , Shafaat Ali , Ulas Jale , Diefes‐Dux Heidi A. 
Published: September 2018

AbstractBackgroundA factor related to students’ course performance that has seen limited research compared to other academic factors is the time of day a class is offered. Because of students’ chronotypes (i.e., preferred time of day to study or work), time of class can influence attendance, which has a strong correlation with students’ performance in a course.Purpose/HypothesisThe goal of this study was to investigate the relationship between class time, students’ attendance including individual and average class attendance, and students’ final grades in an active learning course.Design/MethodThe grade and attendance records of 1,577 first‐year engineering (FYE) students enrolled in 15 sections at different times of the day were analyzed using Tukey's Honestly Significant Difference and Multi‐Level Modeling to identify whether the performance and attendance of students in the early morning sections were significantly different from those in the other sections and to differentiate the individual and class attendance in relation to students’ grades.ResultsStudents enrolled in early morning and late Friday afternoon classes had lower attendance and final grades than students in other sections. Class average attendance had a significant relationship with students’ grades. Thus, in active learning classes, both an individual student's and classmates’ absences have a negative relationship with an individual student's grade.ConclusionFYE students are more likely to miss early morning classes. In a course based on active learning, this lower attendance has a negative relationship with student performance for all students in the class, including the ones who attend the class regularly, suggesting active learning may amplify the negative effects of missing classes.
A Multimodal Exploration of Engineering Students' Emotions and Electrodermal Activity in Design Activities
Authors: Villanueva Idalis , Campbell Brett D. , Raikes Adam C. , Jones Suzanne H. , Putney LeAnn G. 
Published: September 2018

AbstractBackgroundThis exploratory study uses multimodal approaches to explore undergraduate student engagement via topic emotions and electrodermal activity (EDA) in different engineering design method activities and with different instructional delivery formats (e.g., lecture vs. active learning).Purpose/HypothesisThe goal of this research is to improve our understanding of how students respond, via engagement, to their engineering design activities during class. This study hypothesizes that students would experience no self‐reported mean changes in topic emotions from their preassessment scores for each engineering design topic and instructional format nor would electrodermal activities (EDA) associate to these topic emotions throughout the design activities.Design/MethodEighty‐eight freshmen engineering students completed online pretopic and posttopic emotions surveys for five engineering design activities. A subset of 14–18 participants, the focal point of this study, wore an EDA sensor while completing the surveys and participating in these sessions.ResultsPreliminary findings suggest that EDA increased for individual and collaborative active learning activities compared to lectures. No significant changes in EDA were found between individual and collaborative active learning activities. Moderate negative correlations were found between EDA and negative topic emotions in the first engineering design activity but not across the rest. At the end of the semester, active learning activities showed higher effect sizes indicating a re‐enforcement of students' engagement in the engineering design method activities.ConclusionThis study provides initial results showing how multimodal approaches can help researchers understand students' closer‐to‐real‐time engagement in engineering design topics and instructional delivery formats.