bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA TPT1‐AS1 downregulates the microRNA‐770‐5p expression to inhibit glioma cell autophagy and promote proliferation through STMN1 upregulation
Authors: Jia Lei , Song Yuwen , Mu Luyan , Li Qingla , Tang Jiabin , Yang Zhao , Meng Wenjuan 
Published: October 2019

AbstractThrough the microarray analysis, long noncoding RNA TPT1‐AS1 (TPT1‐AS1) was identified in the development of glioma. However, the specific effect of TPT1‐AS1 on glioma autophagy in the recent years has not fully been investigated. Therefore, the purpose of our present study is to investigate the function of TPT1‐AS1 on affecting autophagy of glioma cells through regulation of microRNA‐770‐5p (miR‐770‐5p)‐mediated stathmin 1 (STMN1). Initially, the expression of TPT1‐AS1, miR‐770‐5p, and STMN1 were determined in glioma cell lines, followed by the prediction and validation of their interaction. After that, the effects of TPT1‐AS1, miR‐770‐5p, and STMN1 on the in vitro glioma cell proliferation and autophagy were assessed using EdU assay and macrophage‐derived chemokine (MDC) and on the in vivo tumor development and autophagy were evaluated using a nude mouse xenograft tumor assay and immunofluorescence assay. In comparison with the normal cells, the glioma cells displayed upregulated expression of TPT1‐AS1 and STMN1, but a downregulated miR‐770‐5p expression. miR‐770‐5p, which directly targeted STMN1, could be downregulated by TPT1‐AS1. Subsequently, in glioma cells, TPT1‐AS1 can function to competitively bind to miR‐770‐5p, thus regulatEing STMN1 expression. Moreover, glioma cell proliferation and autophagy could be mediated through the TPT1‐AS1/miR‐770‐5p/STMN1 axis. From our data we conclude an inhibitory function of TPT1‐AS1 in glioma cell autophagy by downregulating miR‐770‐5p and upregulating STMN1, which may be instrumental for the therapeutic targeting and clinical management of glioma.
Identification of a panel of mitotic spindle‐related genes as a signature predicting survival in lung adenocarcinoma
Authors: Zhang Liwen , He Miao , Zhu Wenjing , Lv Xuemei , Zhao Yanyun , Yan Yuanyuan , Li Xueping , Jiang Longyang , Zhao Lin , Fan Yue , Su Panpan , Gao Mengcong , Ma Heyao , Li Kai , Wei Minjie 
Published: October 2019

AbstractLung adenocarcinoma (LUAD) is one of the most malignant tumor types worldwide. Our objective was to identify a genetic signature that could predict the prognosis of patients with LUAD. We extracted gene data sets from The Cancer Genome Atlas and obtained differentially expressed genes that were highly expressed at every stage. These genes were analyzed using gene set enrichment analysis to obtain four biological processes associated with LUAD. Subsequently, Cox univariate and multivariate analyses were performed to generate four optimized models (G2M checkpoint, E2F targets, mitotic spindle, and glycolysis). We identified a mitotic spindle‐related signature (KIF15, BUB1, CCNB2, CDK1, KIF4A, DLGAP5, ECT2, and ANLN), which could be an independent prognostic indicator, to predict the prognosis of patients with LUAD. This new discovery should offer opportunities to explore the pathogenesis of LUAD and prove clinically useful in predicting LUAD patient prognosis.
The potential role of senescence in limiting fibrosis caused by aging
Authors: Meng Xinghua , Wang Haoran , Song Xiaopeng , Clifton Alancia C. , Xiao Jianhua 
Published: October 2019

AbstractFibrosis‐related diseases carry with them a high mortality rate and their morbidity increases with age. Recent findings indicate that induced senescence in myofibroblasts can limit or reduce myocardial fibrosis, cirrhosis, and idiopathic pulmonary fibrosis, while also accelerating wound healing. However, more senescent cells are accumulated as organisms age, which exacerbates aging‐related diseases. These two contradictory theories inspired us to summarize papers on the restrictive effect of senescence on fibrosis and to input the key findings into simple software that we developed to assist with data organization and presentation. In this review, we illustrate that senescent cells secrete more matrix metalloproteinases to solubilize excess collagen, while chemokines and cytokines activate immune cells to eliminate senescent cells. In the elderly, it is perhaps more effective to limit fibrosis by inducing myofibroblast senescence and then removing senescent cells that are not cleared via normal mechanisms by antisenescence therapies.
Long noncoding RNA VCAN‐AS1 contributes to the progression of gastric cancer via regulating p53 expression
Authors: Feng Li , Li Jian , Li Fan , Li Huanqin , Bei Songhua , Zhang Xiaohong , Yang Zhen 
Published: October 2019

AbstractGastric cancer (GC) is one of the most frequent malignancies worldwide. Long noncoding RNAs (lncRNAs) are found to be largely implicated in various cancers, including GC. However, the function of lncRNA VCAN antisense RNA 1 (VCAN‐AS1) in GC remains unclear. Herein, we observed a low level of VCAN‐AS1 in normal gastric tissues through NCBI and UCSC, and that VCAN‐AS1 upregulation in GC tissues was related to poor prognosis by TCGA. Furthermore, VCAN‐AS1 was found markedly enhanced in GC tissues and cell lines, while its upregulation was related with clinical outcomes of GC patients. Besides this, silencing VCAN‐AS1 represses cell proliferation, migration, and invasion but enhances apoptosis. More important, we discovered that VCAN‐AS1 expression was negatively correlated with wild‐type p53 levels in GC tissues and that p53 was negatively modulated by VCAN‐AS1 in GC cells. Furthermore, p53 suppression reversed the repression of VCAN‐AS1 silence on the biological processes of AGS cells. Intriguingly, we identified that both VCAN‐AS1 and TP53 can bind with eIF4A3, one of the core proteins in the exon junction complex. Also, we confirmed that VCAN‐AS1 negatively regulates TP53 expression by competitively binding with eIF4A3. Our findings disclosed that VCAN‐AS1 contributes to GC progression through interacting with eIF4A3 to downregulate TP53 expression, indicating that VCAN‐AS1 is a novel therapeutic strategy for GC treatment.
miR‐181a/b‐5p ameliorates inflammatory response in monocrotaline‐induced pulmonary arterial hypertension by targeting endocan
Authors: Zhao Haiyan , Guo Yun , Sun Yue , Zhang Na , Wang Xiaofei 
Published: October 2019

AbstractPulmonary arterial hypertension (PAH) is a progressive disorder characterized by vascular remodeling, endothelial cell (EC) dysfunction, and inflammation. The roles of microRNAs have received much critical attention. Thus, this study was attempted to show the biological function of miR‐181a/b‐5p (miR‐181a/b) in monocrotaline (MCT)‐induced PAH. Here, rats injected with MCT were used as PAH models. The expression of miR‐181a/b and its effect on PAH pathologies were examined using miR‐181a/b overexpression lentivirus. A luciferase reporter analysis was performed to measure the relationships between miR‐181a/b and endocan. Additionally, primary rat pulmonary arterial endothelial cells (rPAECs) treated with tumor necrosis factor‐α (TNF‐α) were employed to further validate the regulatory mechanism of miR‐181a/b in vitro. Our results showed that miR‐181a/b expression was reduced in PAH, and its upregulation significantly attenuated the short survival period, right ventricular systolic pressure and mean pulmonary artery pressure increments, right ventricular remodeling, and lung injury. Furthermore, the increase of intercellular cell adhesion molecule‐1 (ICAM1) and vascular cell adhesion molecule‐1 (VCAM1) in PAH rats was inhibited by miR‐181a/b overexpression. Similarly, our in vitro results showed that inducing miR‐181a/b suppressed TNF‐α‐stimulated increase of ICAM1 and VCAM1 in rPAECs. Importantly, the increased expression of endocan in PAH model or TNF‐α‐treated rPAECs was restored by miR‐181a/b upregulation. Further analysis validated the direct targeting relationships between miR‐181a/b and endocan. Collectively, this study suggests that miR‐181a/b targets endocan to ameliorate PAH symptoms by inhibiting inflammatory states, shedding new lights on the prevention and treatment of PAH.
LncRNA HOTAIR is a novel endothelial mechanosensitive gene
Authors: da Silva Rodrigo A. , Ferreira Marcel Rodrigues , Gomes Anderson Moreira , Zambuzzi Willian F. 
Published: October 2019

AbstractTo better address whether the long noncoding RNAs (lncRNAs) HOTAIR and HOTTIP are mechanosensitive genes, they were investigated in differentially challenged endothelial cells with respect to a circuit of tensional forces, considering the performance of both arterial and venous endothelial cells. We subjected arterial‐ and venous‐obtained endothelial cells to a circuit of tensional forces within a shear stress model in vitro. Real‐time quantitative polymerase chain reaction analysis indicated that microRNA (miRNA)‐related processing machinery is significantly required in shear stressed arterial endothelial cell metabolism, which orchestrates miRNA (small noncoding RNA) involvement, and their involvement suggests lncRNA involvement. Of lncRNAs HOTAIR and HOTTIP, only HOTAIR was mechanosensitive considering both arterial and venous endothelial cells, presenting a positive correlation between methylation signature and gene expression. Thereafter, using bioinformatics tools, lncRNA HOTAIR was predicted to modulate miRNA185, miRNA‐21, and miRNA23b downregulation. We compared the values of gene expression with a Pearson's correlation test, and expected correlations were observed for miRNA185 (r = 0.8664), miRNA‐21 (r = 0.8605), and miRNA23b (0.9128). Taken together, these findings clearly show that lncRNA HOTAIR responds to the shear stress and emerges as a novel mechanosensitive gene in endothelial cells. Altogether, this understanding of mechanosensitive transcriptional and posttranscriptional control involving HOTAIR can also lead to new forms of therapeutic intervention for various diseases, as well as new strategies for tissue engineering and regenerative medicine.
FHL1 regulates myoblast differentiation and autophagy through its interaction with LC3
Authors: Han Shunshun , Cui Can , He Haorong , Shen Xiaoxu , Chen Yuqi , Wang Yan , Li Diyan , Zhu Qing , Yin Huadong 
Published: October 2019

AbstractFour and a half LIM domain protein 1 (FHL1) belongs to the FHL protein family and is predominantly expressed in skeletal and cardiac muscle. FHL1 acts as a scaffold during sarcomere assembly and plays a vital role in muscle growth and development. Autophagy is key to skeletal muscle development and regeneration, with its dysfunction associated with a range of muscular pathologies and disorders. In this study, we constructed FHL1‐silenced or FHL1‐overexpressed myoblasts to investigate its role in autophagy during the differentiation of chicken myoblasts into myotubules. Our data showed that FHL1 contributes to myoblast differentiation as measured through MyoG, MyoD, Myh3, and Mb mRNA expression, MyoG and MyHC protein expression and the morphological characteristics of myoblasts. The results showed that FHL1 silencing inhibited the expression of ATG5 and ATG7, meanwhile, immunofluorescence and immunoprecipitation showed that FHL1 and LC3 interacted to regulate the correct formation of autophagosomes. FHL1 inhibition increased cleaved caspase‐3 and PARP abundance and promoted myoblast apoptosis. Furthermore, FHL1 rescued skeletal muscle atrophy through regulating the expression of Atrogin‐1 and MuRF1. Taken together, these data suggested that FHL1 regulates chicken myoblast differentiation through its interaction with LC3.
Bone marrow‐derived mesenchymal stem cell‐derived exosomal microRNA‐208a promotes osteosarcoma cell proliferation, migration, and invasion
Authors: Qin Fa , Tang Haoyu , Zhang Yong , Zhang Zhenhua , Huang Pinge , Zhu Jun 
Published: October 2019

AbstractA recent study has discovered that mesenchymal stem cells (MSCs) are recruited into tumors and MSC‐derived exosomes in a novel mechanism of cell‐to‐cell communication in human cancers. Here, in this study, we explore the impact of the microRNA‐208a (miR‐208a)‐enriched exosomes derived from bone marrow‐derived mesenchymal stem cells (BMSCs) on osteosarcoma cells. Human osteosarcoma cells MG‐63 and Saos‐2 were exposed to BMSCs‐derived exosomes treated with either miR‐208a mimic or inhibitor. The MTT assay, transwell migration assay, and soft agar colony formation assay were used to evaluate the viability, migration, and clonogenicity of osteosarcoma cells. Bioinformatics analysis and dual‐luciferase reporter gene assays validated the targeted relationship between miR‐208a and PDCD4. Western blot assay was used to detect the expression of PDCD4 and related proteins in the ERK1/2 pathway in osteosarcoma cells. BMSCs communicated with osteosarcoma cells via exosomes. Ectopic expression of miR‐208a was shown to increase the viability, migration, and clonogenicity of osteosarcoma cells. Analysis of the exosomal content identified miR‐208a as a mediator of the exosomal effects on osteosarcoma cells in part via downregulation of PDCD4 and activating the ERK1/2 pathway. In summary, our study illuminates that BMSC‐derived exosomal miR‐208a enhances the progression of osteosarcoma.
Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway
Authors: Wang Yunjiao , He Gang , Tang Hong , Shi Youxing , Zhu Min , Kang Xia , Bian Xuting , Lyu Jingtong , Zhou Mei , Yang Mingyu , Mu Miduo , Chen Wan , Zhou Binghua , Yuan Chengsong , Zhang Jiqiang , Tang Kanglai 
Published: October 2019

AbstractTendinopathy is a common musculoskeletal system disorder in sports medicine, but regeneration ability of injury tendon is limited. Tendon stem cells (TSCs) have shown the definitive treatment evidence for tendinopathy and tendon injuries due to their tenogenesis capacity. Aspirin, as the representative of nonsteroidal anti‐inflammatory drugs for its anti‐inflammatory and analgestic actions, has been commonly used in treating tendinopathy in clinical, but the effect of aspirin on tenogenesis of TSCs is unclear. We hypothesized that aspirin could promote injury tendon healing through inducing TSCs tenogenesis. The aim of the present study is to make clear the effect of aspirin on TSC tenogenesis and tendon healing in tendinopathy, and thus provide new treatment evidence and strategy of aspirin for clinical practice. First, TSCs were treated with aspirin under tenogenic medium for 3, 7, and 14 days. Sirius Red staining was performed to observe the TSC differentiation. Furthermore, RNA sequencing was utilized to screen out different genes between the induction group and aspirin treatment group. Then, we identified the filtrated molecules and compared their effect on tenogenesis and related signaling pathway. At last, we constructed the tendinopathy model and compared biomechanical changes after aspirin intake. From the results, we found that aspirin promoted tenogenesis of TSCs. RNA sequencing showed that growth differentiation factor 6 (GDF6), GDF7, and GDF11 were upregulated in induction medium with the aspirin group compared with the induction medium group. GDF7 increased tenogenesis and activated Smad1/5 signaling. In addition, aspirin increased the expression of TNC, TNMD, and Scx and biomechanical properties of the injured tendon. In conclusion, aspirin promoted TSC tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.
MKL1 mediates TGF‐β‐induced CTGF transcription to promote renal fibrosis
Authors: Mao Lei , Liu Li , Zhang Tianyi , Wu Xiaoyan , Zhang Tao , Xu Yong 
Published: October 2019

AbstractAberrant fibrogenesis impairs the architectural and functional homeostasis of the kidneys. It also predicts poor diagnosis in patients with end‐stage renal disease (ESRD). Renal tubular epithelial cells (RTEC) can trans‐differentiate into myofibroblasts to produce extracellular matrix proteins and contribute to renal fibrosis. Connective tissue growth factor (CTGF) is a cytokine upregulated in RTECs during renal fibrosis. In the present study, we investigated the regulation of CTGF transcription by megakaryocytic leukemia 1 (MKL1). Genetic deletion or pharmaceutical inhibition of MKL1 in mice mitigated renal fibrosis following the unilateral ureteral obstruction procedure. Notably, MKL1 deficiency in mice downregulated CTGF expression in the kidneys. Likewise, MKL1 knockdown or inhibition in RTEs blunted TGF‐β induced CTGF expression. Further, it was discovered that MKL1 bound directly to the CTGF promoter by interacting with SMAD3 to activate CTGF transcription. In addition, MKL1 mediated the interplay between p300 and WDR5 to regulate CTGF transcription. CTGF knockdown dampened TGF‐β induced pro‐fibrogenic response in RTEs. MKL1 activity was reciprocally regulated by CTGF. In conclusion, we propose that targeting the MKL1–CTGF axis may generate novel therapeutic solutions against aberrant renal fibrogenesis.
Effects of the Fluoroquinolones Moxifloxacin and Levofloxacin on the QT Subintervals: Sex Differences in Ventricular Repolarization
Authors: Täubel Jӧrg , Prasad Krishna , Rosano Giuseppe , Ferber Georg , Wibberley Helen , Cole Samuel Thomas , Van Langenhoven Leen , Fernandes Sara , Djumanov Dilshat , Sugiyama Atsushi 
Published: October 2019

AbstractWomen are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT‐prolonging drugs. The purpose of this study was to characterize the differences in cardiac electrophysiology between moxifloxacin and levofloxacin in men and women and to assess the balance of inward and outward currents through the analysis of QT subintervals. Data from 2 TQT studies were used to investigate the impact of moxifloxacin (400 mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using algorithms for measurement of J‐Tpeak and Tpeak‐Tend intervals. Concentration‐effect analyses were performed to establish potential relationships between the ECG effects and the concentrations of the 2 fluoroquinolones. Moxifloxacin was shown to be a more potent prolonger of QT interval corrected by Fredericia (QTcF) and had a pronounced effect on J‐Tpeakc. Levofloxacin had little effect on J‐Tpeakc. For moxifloxacin, the concentration‐effect modeling showed a greater effect for women on QTcF and J‐Tpeakc, whereas for levofloxacin the inverse was true: women had smaller QTcF and J‐Tpeakc effects. The different patterns in repolarization after administration of both drugs suggested a sex difference, which may be related to the combined IKs and IKr inhibitory properties of moxifloxacin versus IKr suppression only of levofloxacin. The equipotent inhibition of IKs and IKr appears to affect women more than men. Sex hormones are known to influence cardiac ion channel expression and differences in QT duration. Differences in IKr and IKs balances, influenced by sex hormones, may explain the results. These results support the impact of sex differences on the cardiac safety assessment of drugs.
Optimization of selective acidolysis pretreatment for the valorization of wheat straw by a combined chemical and enzymatic process
Authors: Guo Jianming , Huang Kaixuan , Zhang Shizhong , Xu Yong 
Published: October 2019

AbstractBACKGROUNDAdvances in industrial biotechnology offer potential opportunities for economic utilization of abundantly available agricultural crop waste such as wheat straw, which is of great interest for advancement in xylo‐oligosaccharides (XOS) and fermentable monosaccharides. In the present study, crude XOS and fermentable monosaccharides were sequentially produced by a combined chemical and enzymatic process from wheat straw.RESULTSMaximum yield of XOS was 38.2% and the corresponding yield of glucose was 82.7% despite the wax barrier on the surface of wheat straw, while the acetic acid concentration was decreased from 20% to 5%. Pilot scale run produces 91.6 g XOS, 92.5 g xylose and 316.0 g glucose from 1000 g of wheat straw that means the utilization of 78.9% of xylan and 89.7% glucan constitutes.CONCLUSIONBy removal of 65% xylan from wheat straw, enzymatic hydrolysis of cellulose was also improved efficiently although its polymer structure was almost kept inert during acetic acid pretreatment. © 2019 Society of Chemical Industry
Synthesis of spiroindolo[2,1‐b]quinazolines from Huisgen zwitterions and tryptanthrin‐malononitrile adducts
Authors: Yavari Issa , Solgi Raziyeh , Khajeh‐Khezri Aliyeh , Askarian‐Amiri Mohammad , Halvagar Mohammad Reza 
Published: October 2019

AbstractFunctionalized spiroindolo[2,1‐b]quinazolines are obtained from the reaction between tryptanthrin‐malononitrile adducts and Huisgen zwitterionic intermediates, generated by addition reaction of aromatic N‐heterocycles with acetylenic esters. The reaction is diastereoselective leading to the formation of a single diastereoisomer. The structure of a typical product established by X‐ray crystallography.
Eriodictyol and naringenin inhibit the formation of AGEs: An in vitro and molecular interaction study
Authors: Liu Jianli , Yang Zhijun , Cheng Ye , Wu Qiong , He Yin , Li Qijiu , Cao Xiangyu 
Published: October 2019

AbstractMaillard reaction occurs between the carbonyl group of reducing sugars and the free amino groups of protein, which eventually results in the formation and accumulation of advanced glycation end products (AGEs) irreversibly. Excessive production of AGEs is associated with many diseases, such as Alzheimer disease, neuropathy, retinopathy, and nephropathy. In this study, the effects of eriodictyol and naringenin on the inhibition of AGEs were studied with bovine serum albumin (BSA)–methylglyoxal (MGO) model by spectroscopic techniques and molecular docking methods. The fluorescence spectroscopy results suggested that eriodictyol and naringenin could inhibit the formation of AGEs. Circular dichroism (CD) studies indicated that eriodictyol and naringenin could stabilize the structure of BSA and inhibit the formation of AGEs. The molecular docking results demonstrated that eriodictyol formed two hydrogen bonds with Lys 350 and Leu 480 and the main forces were hydrogen bonding and hydrophobic interactions. However, naringenin interacted with Arg 484 of BSA, and the main force was hydrophobic interaction. It can be concluded that eriodictyol and naringenin can inhibit the formation of AGEs and eriodictyol has stronger inhibitory activity of AGEs than that of naringenin, which is probably due to the additional hydroxyl group in the position C‐3′ of B ring of eriodictyol.
A fast MoM solver for wire‐to‐surface junctions in layered uniaxial media
Authors: Zeng Shubin , Wilton Donald R. , Chen Jiefu 
Published: October 2019

AbstractWire‐to‐surface structures in layered uniaxial media are of great importance in practical applications. This paper presents the essential procedures to build a fast method of moments (MoM) solver for modeling wire‐to‐surface structures in layered uniaxial media. These procedures include the modeling of junctions, accelerated evaluation, and efficient interpolation of the layered media Green's function (LMGF), and thin‐wire modeling in layered uniaxial media. Three numerical examples are presented to demonstrate the accuracy and efficiency of our approach.