bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial quality control in cardiac cells: Mechanisms and role in cardiac cell injury and disease
Authors: Tahrir Farzaneh G. , Langford Dianne , Amini Shohreh , Mohseni Ahooyi Taha , Khalili Kamel 
Published: November 2018

AbstractMitochondria play an important role in maintaining cardiac homeostasis by supplying the major energy required for cardiac excitation–contraction coupling as well as controlling the key intracellular survival and death pathways. Healthy mitochondria generate ATP molecules through an aerobic process known as oxidative phosphorylation (OXPHOS). Mitochondrial injury during myocardial infarction (MI) impairs OXPHOS and results in the excessive production of reactive oxygen species (ROS), bioenergetic insufficiency, and contributes to the development of cardiovascular diseases. Therefore, mitochondrial biogenesis along with proper mitochondrial quality control machinery, which removes unhealthy mitochondria is pivotal for mitochondrial homeostasis and cardiac health. Upon damage to the mitochondrial network, mitochondrial quality control components are recruited to segregate the unhealthy mitochondria and target aberrant mitochondrial proteins for degradation and elimination. Impairment of mitochondrial quality control and accumulation of abnormal mitochondria have been reported in the pathogenesis of various cardiac disorders and heart failure. Here, we provide an overview of the recent studies describing various mechanistic pathways underlying mitochondrial homeostasis with the main focus on cardiac cells. In addition, this review demonstrates the potential effects of mitochondrial quality control dysregulation in the development of cardiovascular disease.
Troxerutin attenuates myocardial cell apoptosis following myocardial ischemia‐reperfusion injury through inhibition of miR‐146a‐5p expression
Authors: Shu Liliang , Zhang Wanzhe , Huang Gongcheng , Huang Chen , Zhu Xiaohua , Su Gang , Xu Jing 
Published: November 2018

AbstractThe aim of the current study was to investigate the effects and the underlying mechanisms of troxerutin on myocardial cell apoptosis during ischemia‐reperfusion (I/R) injury. Hypoxia/reoxygenation (H/R) model in neonatal rat cardiomyocytes, and I/R model in rats, were established following troxerutin preconditioning. The quantitative real‐time polymerase chain reaction analysis was performed to examine the messenger RNA miR‐146a‐5p expression in cardiomyocytes and myocardial tissues. Hemodynamic parameters and serum creatine kinase, lactate dehydrogenase, tumor necrosis factor‐α, and interleukin‐10 were evaluated. Infarct size was examined by 2,3,5‐triphenyltetrazolium chloride staining. Besides, myocardial apoptosis was detected by terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the protein levels of caspase‐3, Bax, and Bcl‐2. The results showed that, troxerutin decreased rat cardiomyocyte apoptosis during H/R injury. Furthermore, the antiapoptotic effect of troxerutin against I/R injury was mediated by miR‐146a‐5p downregulation. In vivo experiments suggested that troxerutin alleviated myocardial I/R injury in rats via inhibition of miR‐146a‐5p. In conclusion, troxerutin exerted cardioprotective effects during I/R injury by downregulating miR‐146a‐5p.
A comparison of three strategies for biopanning of phage‐scFv library against diphtheria toxin
Authors: Lakzaei Mostafa , Rasaee Mohhamad Javad , Fazaeli Ali Akbar , Aminian Mahdi 
Published: November 2018

AbstractThe biopanning process is a critical step in phage display for isolating peptides or proteins with specific binding properties. Conventional panning methods are sometimes not so effective and may result in nonspecific or low‐yield positive results. In this study, three different strategies including soluble antibody‐capturing, pH‐stepwise elution, and conventional panning were used for enrichment of specific clones against diphtheria toxoid. The reactivity of the selected clones was evaluated using an indirect enzyme‐linked immunosorbent assay. The positive clones were screened using Vero cell viability assay. The neutralizing clones were expressed in HB2151 strain of Escherichia coli and soluble single‐chain fragment variable (scFv) fragments were purified by nickel‐nitrilotriacetic acid affinity chromatography. Finally, the ability of scFv fragments for neutralizing diphtheria toxin (DT) were evaluated again using Vero cell viability assay. After four rounds of panning, the soluble antibody‐capturing method yielded 15 positive phage‐scFv clones against diphtheria toxoid. Conventional panning and pH‐stepwise elution model resulted from nine and five positive phage‐scFv clones, respectively. Among all positive clones, three clones were able to neutralize DT in Vero cell viability assay. Two of these clones belonged to a soluble antibody‐capturing method and one of them came from conventional panning. Three neutralizing clones were used for soluble expression and purification of scFvs fragments. It was found that these soluble scFv fragments possessed neutralizing activity ranging from 0.15 to 0.6 µg against two‐fold cytotoxic dose 99% of DT. In conclusion, the results of our study indicate that soluble antibody‐capturing method is an efficient method for isolation of specific scFv fragments.
Aβ stimulates microglial activation through antizyme‐dependent downregulation of ornithine decarboxylase
Authors: Cheng Yu‐Wen , Chang Chun‐Cheng , Chang Ti‐Sheng , Li Hsin‐Hua , Hung Hui‐Chih , Liu Guang‐Yaw , Lin Chih‐Li 
Published: November 2018

AbstractAlzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Its pathology is associated with the deposition of amyloid β (Aβ), an abnormal extracellular peptide. Moreover, its pathological progression is closely accompanied by neuroinflammation. Specifically, Aβ‐associated microglial overactivation may have the central role in AD pathogenesis. Interestingly, arginine metabolism may contribute to the equilibrium between M1 and M2 microglia. However, little is known about the involvement of arginine metabolism in Aβ‐induced microglial neuroinflammation and neurotoxicity. Moreover, the underlying mechanism by which Aβ induces the transition of microglia to the M1 phenotype remains unclear. In this study, we investigated the role of Aβ in mediating microglial activation and polarization both in vitro and in vivo. Our results demonstrated that under the Aβ treatment, ornithine decarboxylase (ODC), a rate‐limiting enzyme in the regulation of arginine catabolism, regulates microglial activation by altering the antizyme (AZ) + 1 ribosomal frameshift. Furthermore, the restoration of ODC protein expression levels has profound effects on inhibition of Aβ‐induced M1 markers and thus attenuates microglial‐mediated cytotoxicity. Altogether, our findings suggested that Aβ may contribute to M1‐like activation by disrupting the balance between ODC and AZ in microglia.
Prognostic value of a gene signature in clear cell renal cell carcinoma
Authors: Chen Liang , Luo Yongwen , Wang Gang , Qian Kaiyu , Qian Guofeng , Wu Chin‐Lee , Dan Han C. , Wang Xinghuan , Xiao Yu 
Published: November 2018

AbstractRenal cancer is a common urogenital system malignance. Novel biomarkers could provide more and more critical information on tumor features and patients’ prognosis. Here, we performed an integrated analysis on the discovery set and established a three‐gene signature to predict the prognosis for clear cell renal cell carcinoma (ccRCC). By constructing a LASSO Cox regression model, a 3‐messenger RNA (3‐mRNA) signature was identified. Based on the 3‐mRNA signature, we divided patients into high‐ and low‐risk groups, and validated this by using three other data sets. In the discovery set, this signature could successfully distinguish between the high‐ and low‐risk patients (hazard ratio (HR), 2.152; 95% confidence interval (CI),1.509–3.069; p < 0.0001). Analysis of internal and two external validation sets yielded consistent results (internal: HR, 2.824; 95% CI, 1.601–4.98;
p < 0.001; GSE29609: HR, 3.002; 95% CI, 1.113–8.094;
p = 0.031; E‐MTAB‐3267: HR, 2.357; 95% CI, 1.243–4.468;
p = 0.006). Time‐dependent receiver operating characteristic (ROC) analysis indicated that the area under the ROC curve at 5 years was 0.66 both in the discovery and internal validation set, while the two external validation sets also suggested good performance of the 3‐mRNA signature. Besides that, a nomogram was built and the calibration plots and decision curve analysis indicated the good performance and clinical utility of the nomogram. In conclusion, this 3‐mRNA classifier proved to be a useful tool for prognostic evaluation and could facilitate personalized management of ccRCC patients.
Chloroquine inhibits human retina pigmented epithelial cell growth and microtubule nucleation by downregulating p150glued
Authors: Chen Ting‐Yu , Lien Wei‐Chih , Cheng Hui‐Ling , Kuan Ta‐Shen , Sheu Shi‐Yuan , Wang Chia‐Yih 
Published: November 2018

AbstractChloroquine (CQ) is an antimalaria drug that has been used in clinical practice for several decades. One serious complication of CQ treatment is the macular retinopathy caused by the disruption of the retinal pigmented epithelium, leading to vision loss. Little is known about how CQ affects retinal pigmented epithelium. In this study, we found that cell proliferation was reduced by CQ treatment in time and dose‐dependent manners. No obvious cell death was detected; however, what was observed instead was G0/G1 arrest during which primary cilium started to grow in the presence of CQ. Pharmacological inhibition of primary cilium formation led to a reduction of cell viability suggesting that CQ‐induced primary cilium protected cells from death. In addition to cell growth, with the CQ treatment the retina pigmented epithelium (RPE) cells less flattened with the spindle‐like protrusion. When checking the microtubule networks, the microtubule nucleation activity was disrupted in the presence of CQ. The level of p150
glued, the largest subunit of dynactin, was reduced in CQ‐treated RPE1 cells, and depletion of p150
glued resulted in a phenotype reminiscent of CQ‐treated cells. Thus, CQ treatment reduced the expression of p150
glued, leading to reduced S phase entry and defective microtubule nucleation.
CircRNA circPDSS1 promotes the gastric cancer progression by sponging miR‐186‐5p and modulating NEK2
Authors: Ouyang Yiming , Li Yuejin , Huang Yingguang , Li Xing , Zhu Yu , Long Yaxin , Wang Yongzhi , Guo Xiaodong , Gong Kunmei 
Published: November 2018

AbstractThe aim of this study is to investigate the regulatory mechanism of circPDSS1/miR‐186‐5p/NEK2 axis on the viability and proliferation in gastric cancer (GC) cell line. Differentially expressed circRNAs, miRNAs, and mRNAs in GC tissues and paracarcinoma tissues were analyzed using gene chips GSE83521, GSE89143, and GSE93415. Then, the expression of circPDSS1, miR‐186‐5p, and NEK2 was analyzed via quantitative real‐time polymerase chain reaction (qRT‐PCR). Survival analysis was adopted to explore the association between the circPDSS1 expression and the prognosis of GC. The effect of circPDSS1 on GC cell cycle and apoptosis was verified with the flow cytometry. Targeting relationships among circPDSS1, miR‐186‐5p, and NEK2 were predicted via bioinformatics analysis and demonstrated by the dual‐luciferase reporter assay. Our results showed that circPDSS1 and NEK2 were high‐expressed whereas miR‐186‐5p was low‐expressed in GC tissues and cells. CircPDSS1 promoted GC cell cycle and inhibited apoptosis by sponging miR‐186‐5p, while miR‐186‐5p inhibited cell cycle and promoted apoptosis by targeting NEK2. Thus, circPDSS1 acts as a tumor promoter by regulating miR‐186‐5p and NEK2, which could be a potential biomarker and therapeutic target for the management of GC.
Exosomes derived from acute myeloid leukemia cells promote chemoresistance by enhancing glycolysis‐mediated vascular remodeling
Authors: Wang Bin , Wang Xiaoting , Hou Diyu , Huang Qian , Zhan Weiwu , Chen Canwei , Liu Jingru , You Ruolan , Xie Jieqiong , Chen Ping , Huang Huifang 
Published: November 2018

AbstractAcute myeloid leukemia (AML) is the most common type of leukemia in adults. AML cells secrete angiogenic factors to remodel vasculature and acquire chemoresistance; however, antiangiogenic drugs are often ineffective in AML treatment. Cancer cell‐derived exosomes can induce angiogenesis, but their role in vascular remodeling during AML is unclear. Here, we found that exosomes secreted by AML cells promoted proliferation and migration and tube‐forming activity of human umbilical vein endothelial cells (HUVECs), whereas HUVECs conferred chemoresistance to AML cells. AML cell‐derived exosomes contained vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) messenger RNA and induced VEGFR expression in HUVECs. Furthermore, they enhanced glycolysis, which correlated with HUVEC proliferation, tube formation, and resistance to apoptosis. Thus, AML cells secrete VEGF/VEGFR‐containing exosomes that induce glycolysis in HUVECs leading to vascular remodeling and acquisition of chemoresistance. These findings may contribute to the development of novel therapeutic strategies targeting exosomes in AML.
Overexpression of novel lncRNA NLIPMT inhibits metastasis by reducing phosphorylated glycogen synthase kinase 3β in breast cancer
Authors: Jiang Yang , Lin Lili , Zhong Shen , Cai Yangjun , Zhang Fen , Wang Xiaobo , Miao Rongrong , Zhang Baodan , Gao Shenmeng , Hu Xiaoqu 
Published: November 2018

AbstractLong noncoding RNAs (lncRNAs) are considered as regulators of gene expression in cancers. However, cancer profiling has little focused on noncoding genes. Here, we reported that RP11–115N4.1 (here renamed novel lncRNA inhibiting proliferation and metastasis [NLIPMT]) was downregulated in breast cancer tissues. Ectopic expression of NLIPMT inhibited mammary cell proliferation, motility in vitro. Moreover, lnc‐NLIPMT reduced the growth of implanted MDA‐MB‐231 cells in vivo. Mechanistically, glycogen synthase kinase 3β (GSK3β) was identified as an effector protein regulated by lnc‐NLIPMT. Inhibition of GSK3β activity restored NLIPMT‐induced inhibition of proliferation and motility in breast cancer cells. These data reveal that lnc‐NLIPMT functions as a driver of breast cancer progression and might serve as a potential target for antimetastatic therapies.
Cancer stem cells (CSCs) in cancer progression and therapy
Authors: Najafi Masoud , Farhood Bagher , Mortezaee Keywan 
Published: November 2018

AbstractCancer stem cells (CSCs) are self‐renewable cell types that are identified in most types of liquid and solid cancers and contributed to tumor onset, expansion, resistance, recurrence, and metastasis after therapy. CSCs are identified from the expression of cell surface markers, which is tumor‐type dependent. The transition between CSCs with cancer cells and other non‐CSCs occurs in cancers, which is possibly under the control of signals from CSCs and tumor microenvironment (TME), including CSC niche. Cancer‐associated fibroblasts are among the most influential cells for promoting both differentiation of CSCs and dedifferentiation of non‐CSCs toward attaining a CSC‐like phenotype. WNT/β‐catenin, transforming growth factor‐β, Hedgehog, and Notch are important signals for maintaining self‐renewal in CSCs. An effective therapeutic strategy relies on targeting both CSCs and non‐CSCs to remove a possible chance of tumor relapse. There are multiple ways to target CSCs, including immunotherapy, hormone therapy, (mi)siRNA delivery, and gene knockout. Such approaches can be designed for suppressing CSC stemness, tumorigenic cues from TME, CSC extrinsic and/or intrinsic signaling, hypoxia or for promoting differentiation in the cells. Because of sharing a range of characteristics to normal stem/progenitor cells, CSCs must be targeted based on their unique markers and their preferential expression of antigens.
Clonal hematopoiesis: Genes and underlying mechanisms in cardiovascular disease development
Authors: Haybar Habib , Shahrabi Saeid , Ghanavat Majid , Khodadi Elahe 
Published: November 2018

AbstractThe clonal hematopoiesis when occurring without hematologic abnormalities is defined as clonal hematopoiesis of indeterminate potential (CHIP). Aging causes accumulation of somatic mutations, and hematopoietic stem cells (HSCs) can develop clonal expansion of different lineages by these mutations. CHIP has a correlation with cancer and cardiovascular disease (CVD) through acquired mutations in genes. DNMT3A, TET2, ASXL1, and JAK2 genes as well as other genes are the most common somatic mutations causing CHIP and CVD in an older age. Other factors such as cholesterol level, laboratory tests and indexes also affect CVD. In addition, mutations in adenosine triphosphate–binding cassette transporters and also chronic stress in nervous system can result in HSCs proliferation and CVD. However, laboratory tests and indexes are not sensitive for CVD diagnosis. But the therapeutic interventions can be helpful to prevent CVD cases by targeting somatic mutations, chemokine receptors, and growth factors in HSCs. Also, new drugs can control CVD by targeting of cells and their signaling pathways in HSCs. Therefore, more investigations are needed and more questions should be answered for the relationship between CHIP and CVD as a challenging issue in future.
Optimal SSA‐based wideband digital differentiator design for cardiac QRS complex detection application
Authors: Nayak Chandan , Saha Suman Kumar , Kar Rajib , Mandal Durbadal 
Published: November 2018

AbstractIn this paper, a computationally efficient, highly accurate, wideband, stable, and minimum phase infinite impulse response type first‐order digital differentiator (DD) is designed by employing a swarm intelligence‐based search method called Salp Swarm Algorithm (SSA) for the QRS complex detection application. The optimal coefficients of the DD are computed by minimizing a suitable fitness function to meet the ideal differentiator magnitude response characteristics. The simulation results and the root mean square magnitude error metric justify the superiority of the proposed SSA‐based DD design as compared with all other differentiators employed in the QRS complex detection application, and the reported first‐order DDs based on the numerical methods and the other evolutionary algorithms. The electrocardiogram signal is preprocessed by the proposed DD to generate the feature signal corresponding to each QRS complex. The generated feature signal is used as a marker to identify the exact occurrence of the QRS complex by using an adaptive threshold‐based detection logic. The proposed DD‐based QRS detection approach achieves a sensitivity (Se), positive prediction (PP), detection error rate (DER), and accuracy (Acc) of 99.94%, 99.93%, 0.1279%, and 99.87%, respectively, when validated against MIT/BIH arrhythmia database. Also, against the QT database, the proposed QRS detector produces a Se of 99.93%, PP of 99.97%, DER of 0.09%, and Acc of 99.90%. The performance of the proposed QRS detection technique is compared with the methods already reported in the recent literature, and the superiority of the proposed approach is established with respect to different standard performance metrics. The noise tolerance capability of the proposed QRS detector is demonstrated against MIT/BIH noise stress test database.
A Review of Articles Using Observation Methods to Study Creativity in Education (1980–2018)
Authors: Katz‐Buonincontro Jen , Anderson Ross C. 
Published: November 2018

AbstractThis paper reports on an integrative literature review of published articles that used either quantitative or qualitative observation methods to research creativity in learning contexts. Observation is an empirical research method used in quantitative and qualitative naturalistic studies focused on understanding behavior and interactions as they unfold in real‐time, which makes it particularly salient for examining the processes associated with the generation and adoption of creative ideas. However, observation remains underutilized in the field of creativity studies, partly because data collection can be time and resource intensive, but also because there are a lack of protocols and recommended research practices for observing creative thinking and problem solving in an educational environment that covers all phases of design, collection, analysis, and reporting. Thirty‐seven articles from 1980–2018 were reviewed along seven dimensions: definition of creativity, unit of observation, observer role, observation sampling method, research design, data collection, and data analysis. The paper concludes with five recommendations for using observation to advance the state of research on creativity and education.
Gender Differences in the Creativity–Academic Achievement Relationship: A Study from China
Authors: Zhang Wenjing , Ren Ping , Deng Lifang 
Published: November 2018

AbstractThis study investigated gender differences in the relationship between creativity and academic achievement. A sample of 1082 primary students participated in this study in Beijing, China. Their age ranged between 8 and 15 years old (M = 10.41, SD = 0.99). Students’ creativity was measured by the Chinese version of the Torrance Test of Creative Thinking Figural Form A, and academic achievement was based on students’ self‐reported grades of last semester. Results revealed that there was a significantly positive relationship between creativity and academic achievement, ranging from r = .07 to r = .21. Gender differences regarding which aspects of creativity were related to academic achievement were also found. Plausible explanations and implications of the findings in creativity research and education are discussed.