bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analysis of a competing endogenous RNA network reveals key long noncoding RNAs as potential prognostic biomarkers for hepatocellular carcinoma
Authors: Ye Jiaxiang , Zhang Jinyan , Lv Yufeng , Wei Jiazhang , Shen Xiaoyun , Huang Junqi , Wu Susu , Luo Xiaoling 
Published: April 2019

AbstractGrowing evidence has revealed that long noncoding RNAs (lncRNAs) have an important impact on tumorigenesis and tumor progression via a mechanism involving competing endogenous RNAs (ceRNAs). However, their use in predicting the survival of a patient with hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to develop a novel lncRNA expression–based risk score system to accurately predict the survival of patients with HCC. In our study, using expression profiles downloaded from The Cancer Genome Atlas database, the differentially expressed messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs) were explored in patients with HCC and normal liver tissues, and then a ceRNA network constructed. A risk score system was established between lncRNA expression of the ceRNA network and overall survival (OS) or recurrence‐free survival (RFS); it was further analyzed for associations with the clinical features of patients with HCC. In HCC, 473 differentially expressed lncRNAs, 63 differentially expressed miRNAs, and 1417 differentially expressed mRNAs were detected. The ceRNA network comprised 41 lncRNA nodes, 12 miRNA nodes, 24 mRNA nodes, and 172 edges. The lncRNA expression–based risk score system for OS was constructed based on six lncRNAs (MYLK‐AS1, AL359878.1, PART1, TSPEAR‐AS1, C10orf91, and LINC00501), while the risk score system for RFS was based on four lncRNAs (WARS2‐IT1, AL359878.1, AL357060.1, and PART1). Univariate and multivariate Cox analyses showed the risk score systems for OS or RFS were significant independent factors adjusted for clinical factors. Receiver operating characteristic curve analysis showed the area under the curve for the risk score system was 0.704 for OS, and 0.71 for RFS. Our result revealed a lncRNA expression–based risk score system for OS or RFS can effectively predict the survival of patients with HCC and aid in good clinical decision‐making.
microRNA‐146a downregulates IL‐17 and IL‐35 and inhibits proliferation of human periodontal ligament stem cells
Authors: Zhao Sen , Cheng Yawei , Kim Jong Ghee 
Published: April 2019

AbstractPeriodontitis is characterized by increased levels of proinflammatory factors, such as interleukin‐17 (IL‐17) and IL‐35. In this study, the expression of microRNA‐146a (miRNA‐146a), IL‐17, and IL‐35 in the plasma of patients with periodontitis and healthy controls were detected by quantitative reverse transcription polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. miRNA‐146a mimic was transfected into periodontal ligament stem cells (PDLSCs) isolated from periodontitis‐affected teeth and healthy teeth. Cell proliferation and expression of IL‐17 and IL‐35 were detected by cell counting kit‐8 assay and Western blot analysis, respectively. It was observed that miRNA‐146a was downregulated but IL‐17 and IL‐35 were upregulated in the plasma of patients with periodontitis than in healthy controls. miRNA‐146a was inversely correlated with IL‐17 and IL‐35 in patients with periodontitis. miRNA‐146a overexpression inhibited proliferation of PDLSCs derived from both periodontitis‐affected teeth and healthy teeth. miRNA‐146a overexpression led to downregulated IL‐17 and IL‐35 expression in PDLSCs isolated from periodontitis‐affected teeth. We, therefore, conclude that miRNA‐146a may improve periodontitis by downregulating IL‐17 and IL‐35 expression and inhibiting proliferation of human PDLSCs.
Retracted: Vinculin promotes gastric cancer proliferation and migration and predicts poor prognosis in patients with gastric cancer
Authors: Zhang Mingming , Liu Pei , Xu Famei , He Yuanlong , Xie Xiangjun , Jiang Xiangjun 
Published: April 2019

AbstractVinculin is a highly conserved protein involved in cell proliferation, migration, and adhesion. However, the effects of vinculin on gastric cancer (GC) remain unclear. Therefore, we aimed to explore the functional role of vinculin in GC, as well as its underlying mechanism. Expression of vinculin in patients with GC was analyzed by real‐time polymerase chain reaction, Western blot analysis, and immunohistochemistry. Overall survival was evaluated by the Kaplan‐Meier method with the log‐rank test. The relationship between vinculin and clinicopathological characteristics of patients with GC was further identified. In addition, we assessed the expression of vinculin in GC cell lines. Besides, vinculin was suppressed or overexpressed by transfection with small interfering (si‐vinculin) or pcDNA‐vinculin and then cell viability, cell apoptosis, and/or migration was respectively examined by the 3‐(4, 5‐dimethylthiazole‐2‐yl)‐2, 5‐biphenyl tetrazolium bromide assay, flow cytometer, and scratch assay, respectively. Moreover, the cell cycle‐ and apoptosis‐related proteins were detected by Western blot analysis. The expression of vinculin was significantly increased in the GC tissues and cells compared with the nontumor tissues or cells. Vinculin protein positive staining was mainly located in the cell membrane and cytoplasm. Moreover, vinculin was significantly associated with Tumor Node Metastasis (TNM) and poor differentiation. Patients with high vinculin levels had significantly worse overall survival than those with low levels. Suppression of vinculin significantly decreased cell viability and migration and promoted cell apoptosis. However, overexpression of vinculin statistically increased cell viability but had no effects on cell apoptosis. Vinculin promotes GC proliferation and migration and predicts poor prognosis in patients with GC.
Long noncoding RNA myocardial infarction associated transcript promotes the development of thoracic aortic by targeting microRNA‐145 via the PI3K/Akt signaling pathway
Authors: Chen Shiyuan , Chen Hu , Yu Chaowen , Lu Ran , Song Tao , Wang Xiaogao , Tang Wenbo , Gao Yong 
Published: April 2019

AbstractThe main aim of our study was to investigate the roles and molecular basis of long noncoding RNA myocardial infarction associated transcript (MIAT) in the development of thoracic aortic aneurysm. RT‐qPCR assay was performed to measure the expressions of MIAT, microRNA‐145 (miR‐145), along with Bcl‐2 and Bcl‐xl messenger RNAs. Western blot assay was conducted to determine protein levels of Bcl‐2, Bcl‐xl, phosphorylated‐Akt (p‐Akt), and total Akt (t‐Akt). Cell viability was detected by the (3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay. The relationship of MIAT and miR‐145 was examined by bioinformatics analysis and luciferase reporter assay. MIAT expression was significantly increased, and miR‐145 expression was markedly reduced in thoracic aortic aneurysms compared with normal thoracic aortic tissues. MIAT overexpression or miR‐145 depletion improved cell viability and inhibited cell apoptosis in human aortic vascular smooth muscle cells (h‐VSMCs). Further exploration revealed that MIAT could inhibit miR‐145 expression by direct interaction. And miR‐145 upregulation abrogated MIAT‐induced viability increase and apoptosis inhibition in h‐VSMCs. Moreover, MIAT inhibited the activation of Akt signaling, while this effect was abated by miR‐145 overexpression in h‐VSMCs. The inhibition of the Akt pathway by MK‐22062HCl resulted in the reduction of cell viability and the increase of cell apoptotic activity in h‐VSMCs. Akt activation by HY‐18749 improved cell viability and suppressed cell apoptosis in h‐VSMCs. And the introduction of HY‐18749 raised cell viability and curbed cell apoptosis in h‐VSMCs cotransfected with MIAT overexpression plasmid and miR‐145 mimic. lncRNA‐MIAT could target miR‐145 to affect the viability and apoptosis of h‐VSMCs, which was implicated in the regulation of the PI3K/Akt signaling pathway.
Human umbilical cord mesenchymal stem cells derived exosomes exert antiapoptosis effect via activating PI3K/Akt/mTOR pathway on H9C2 cells
Authors: Liu Hui , Sun Xiaolu , Gong Xuhe , Wang Guogan 
Published: April 2019

AbstractBackground/ObjectivesIn recent years, as an alternative to stem cell therapy for cardiovascular diseases (CVD), exsomes have attracted wide attention among researchers. The present study aimed to investigate the role of human umbilical cord mesenchymal stem cells (UC‐MSCs) derived exosomes play on H9C2 cells apoptosis and possible mechanisms.MethodsExosomes were isolated from normal UC‐MSCs culture media and hypoxic preconditioning culture media. Transmission electron microscopy was used to observe the morphology of exosomes. Nanoparticle tracking analysis was used to detect the size distribution and concentration of exosomes. Western blot analysis was used to analyzed the surface marker CD63 of exosomes. H9C2 cells were induced apoptosis by hypoxia and serum deprivation (H/SD) and then were treated respectively by group. Cell Counting Kit‐8 assay was used to detect viability of H9C2 cells. Apoptosis was detected by Hochest staining and annexin V‐FITC/PI. The expression levels of related proteins of apoptosis, autophagy, and PI3K/Akt/mTOR pathway were analyzed by Western blot analysis. Immunofluorescence was used to analyze LC3B expression.ResultsHypoxic preconditioning increased the exosomes secretion of UC‐MSCs. UC‐MSCs derived exosomes could inhibit H/SD‐induced H9C2 cells apoptosis. Hypoxic preconditioning strengthened this antiapoptosis effect of UC‐MSCs. Hypoxic preconditioning UC‐MSCs derived exosomes (H‐Exo) downregulated LC3B‐II/I and beclin‐1 and upregulated P62, p‐Akt/Akt and p‐mTOR/mTOR. The antiapoptotic effect of H‐Exo could be attenuated by treatment with LY294002 and rapamycin.ConclusionUC‐MSCs derived exosomes could inhibit H9C2 cells apoptosis induced by H/SD through regulating autophagy via PI3K/Akt/mTOR pathway. Hypoxia preconditioning could enhance above effects through increasing exosomes secretion of UC‐MSCs.
microRNA‐340‐5p inhibits hypoxia/reoxygenation‐induced apoptosis and oxidative stress in cardiomyocytes by regulating the Act1/NF‐κB pathway
Authors: Li Dong , Zhou Jian , Yang Baoping , Yu Yan 
Published: April 2019

AbstractMicroRNAs (miRNAs) have been reported to play critical roles in the occurrence, progression, and treatment of many cardiovascular diseases. However, the molecular mechanism by which miRNA regulates target gene expression in ischemia‐reperfusion (I/R) injury in acute myocardial infarction (AMI) is not entirely clear. MiR‐340‐5p was reported to be downregulated in acute ischemic stroke. However, it still remains unknown whether miR‐340‐5p is mediated in the pathogenesis process of I/R injury after AMI. In the present study, male C57BL/6 J mice and H9C2 cardiomyocytes were used as experimental models. Real‐time polymerase chain reaction analysis, Western blot analysis, and the terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end‐labeling immunofluorescence staining assay were conducted to examine related indicators in the study. We confirmed that the expression of miR‐340‐5p is downregulated after I/R in AMI mice and hypoxia/reperfusion (H/R)‐induced cardiomyocytes. miR‐340‐5p could inhibit apoptosis and oxidative stress in H/R‐induced H9C2 cells via downregulating activator 1 (Act1). The inhibiting action of miR‐340‐5p on H/R‐induced apoptosis and oxidative stress in cardiomyocytes was partially reversed after Act1 overexpression. Moreover, the results showed that the NF‐κB pathway may be mediated in the role of miR‐340‐5p on H/R‐induced cardiomyocyte apoptosis and oxidative stress. We demonstrated that upregulation of miR‐340‐5p suppresses apoptosis and oxidative stress induced by H/R in H9C2 cells by inhibiting Act1. Therapeutic strategies that target miR‐340‐5p, Act1, and the NF‐κB pathway could be beneficial for the treatment of I/R injury after AMI.
UHRF1 is regulated by miR‐124‐3p and promotes cell proliferation in intrahepatic cholangiocarcinoma
Authors: Zhu Mengxuan , Wei Chuanyuan , Lin Jiajia , Dong Shuangshuang , Gao Dongmei , Chen Jie , Zhao Yan , Liu Binbin 
Published: April 2019

AbstractUbiquitin‐like with PHD and ring finger domains 1 (UHRF1) is abnormally overexpressed in multiple cancers and closely correlated with tumor‐promoting effects, such as high proliferation. However, how UHRF1 functions in intrahepatic cholangiocarcinoma (ICC) has not yet been determined. Herein, we found that UHRF1 is overexpressed in ICC tissues. Downregulated UHRF1 attenuated the transition of the G1/S cell cycle and then suppressed cell proliferation in vitro and tumor growth in vivo. Moreover, upstream regulators of the UHRF1 expression were predicted, and we found that direct binding of miR‐124‐3p inhibited the UHRF1 expression. Elevated miR‐124‐3p suppressed proliferation and led to the arrest of the cell cycle. Furthermore, the expression of UHRF1 was positively correlated with PCNA. Clinically, we showed that elevated UHRF1 was associated with poor prognosis, and served as an independent prognostic factor in ICC patients. Together, these findings demonstrate that UHRF1, regulated by miR‐124‐3p, acts as a tumor promoter by promoting cell proliferation in ICC.
Hypoxic regulation of angiotensin‐converting enzyme 2 and Mas receptor in human CD34+ cells
Authors: Joshi Shrinidh , Wollenzien Hannah , Leclerc Estelle , Jarajapu Yagna PR 
Published: April 2019

AbstractCD34+ hematopoietic stem/progenitor cells (HSPCs) are vasculogenic and hypoxia is a strong stimulus for the vasoreparative functions of these cells. Angiotensin‐converting enzyme 2 (ACE2)/angiotensin‐(1–7)/Mas receptor (MasR) pathway stimulates vasoprotective functions of CD34+ cells. This study tested if ACE2 and MasR are involved in the hypoxic stimulation of CD34+ cells. Cells were isolated from circulating mononuclear cells derived from healthy subjects (n = 46) and were exposed to normoxia (20% O2) or hypoxia (1% O2). Luciferase reporter assays were carried out in cells transduced with lentivirus carrying ACE2‐ or MasR‐ or a scramble‐3′‐untranslated region gene with a firefly luciferase reporter. Expressions or activities of ACE, angiotensin receptor Type 1 (AT1R), ACE2, and MasR were determined. In vitro observations were verified in HSPCs derived from mice undergoing hindlimb ischemia (HLI). In vitro exposure to hypoxia‐increased proliferation and migration of CD34+ cells in basal conditions or in response to vascular endothelial growth factor (VEGF) or stromal‐derived factor 1α (SDF) compared with normoxia. Expression of ACE2 or MasR was increased relative to normoxia while ACE or AT1R expressions were unaltered. Luciferase activity was increased by hypoxia in cells transfected with the luciferase reporter plasmids coding for the ACE2‐ or MasR promoters relatively to the control. The effects of hypoxia were mimicked by VEGF or SDF under normoxia. Hypoxia‐induced ADAM17‐dependent shedding of functional ACE2 fragments. In mice undergoing HLI, increased expression/activity of ACE2 and MasR were observed in the circulating HSPCs. This study provides compelling evidence for the hypoxic upregulation of ACE2 and MasR in CD34+ cells, which likely contributes to vascular repair.
PPARγ promotes diabetes‐associated centrosome amplification via increasing the expression of SKA1 directly at the transcriptional level
Authors: Liu Qin Qin , Wang Pu , He Qin Ju , Ma Ronald , Lee Shao Chin 
Published: April 2019

AbstractWe have recently published that type 2 diabetes can induce cell centrosome amplification due to the action of high glucose, palmitic acid, and insulin, and ROCK1 and 14‐3‐3σ are signal mediators. In this study, we further investigated the molecular mechanisms of the centrosome amplification in colon cancer HCT116 cells. Treatment of the cells with high glucose, palmitic acid, and insulin increased the expression of peroxisome proliferator‐activated receptor γ (PPARγ) as well as the spindle and kinetochore associated protein 1 (SKA1), knockdown of each of which resulted in the inhibition of the treatment‐triggered centrosome amplification. Knockdown of PPARγ inhibited the treatment‐evoked increase in the SKA1 level, whereas knockdown of SKA1 did not modify the treatment‐increased PPARγ level. We found a predicted binding site for PPARγ in the promoter region of the SKA1 gene from the JASPAR database. Experimental results showed that the treatment increased the messenger RNA level of SKA1, which could be inhibited by PPARγ chemical inhibitor or small interfering RNA. Moreover, we were able to show that PPARγ could bind to the binding site in the SKA1 gene promoter, which was increased by the experimental treatment. In conclusion, it is suggested that the pathophysiological factors in type 2 diabetes, high glucose, palmitic acid, and insulin, induce the cell centrosome amplification through the PPARγ‐SKA1 pathway, in which PPARγ increases the expression of SKA1 via directly enhancing the SKA1 gene transcription.
Non‐viral gene delivery for cancer immunotherapy
Authors: Wang Weiqi , Saeed Madiha , Zhou Yao , Yang Lili , Wang Dangge , Yu Haijun 
Published: April 2019

AbstractRecent decades have witnessed the revolutionary development of cancer immunotherapies, which boost cancer‐specific immune responses for long‐term tumor regression. However, immunotherapy still has limitations, including off‐target side effects, long processing times and limited patient responses. These disadvantages of current immunotherapy are being addressed by improving our understanding of the immune system, as well as by establishing combinational approaches. Advanced biomaterials and gene delivery systems overcome some of these delivery issues, harnessing adverse effects and amplifying immunomodulatory effects, and are superior to standard formulations with respect to eliciting antitumor immunity. Nucleic acid‐based nanostructures have diverse functions, ranging from gene expression and gene regulation to pro‐inflammatory effects, as well as the ability to specifically bind different molecules. A brief overview is provided of the recent advances in the non‐viral gene delivery methods that are being used to activate cancer‐specific immune responses. Furthermore, the tumor microenvironment‐responsive synergistic strategies that modulate the immune response by targeting various signaling pathways are discussed. Nanoparticle‐based non‐viral gene delivery strategies have great potential to be implemented in the clinic for cancer immunotherapy.
Low risk of neurodevelopmental impairment among perinatally acquired HIV‐infected preschool children who received early antiretroviral treatment in Thailand
Authors: Jantarabenjakul Watsamon , Chonchaiya Weerasak , Puthanakit Thanyawee , Theerawit Tuangtip , Payapanon Jesdaporn , Sophonphan Jiratchaya , Veeravigom Montida , Jahanshad Neda , Thompson Paul M , Ananworanich Jintanat , Malee Kathleen , Pancharoen Chitsanu ,   the DOET study
Published: April 2019

AbstractIntroductionAntiretroviral therapy (ART) is recommended in perinatally HIV‐infected (PHIV) infants immediately upon diagnosis. We aimed to compare neurodevelopmental outcomes between PHIV children who initiated ART within 12 months of life and perinatally HIV‐exposed uninfected (PHEU) children and to assess neurodevelopmental outcomes by timing of ART.MethodsThis prospective cohort study included Thai children aged 12 to 56 months who were assessed with the Mullen Scales of Early Learning (MSEL) at enrolment and at 48 weeks. Global Developmental Impairment (GDI) was defined as Early Learning Composite (ELC) ≤ 70 on the MSEL; typical developmental pattern was defined as ELC > 70 at both visits. Logistic regression was used to compare prevalence of any GDI. Predictors of changing ELC scores were analysed with generalized estimating equations linear regression model.ResultsFrom 2016 to 2017, 50 PHIV (twenty‐seven early ART within three months and twenty‐three standard ART within three to twelve months) and 100 PHEU children were enrolled. Median (IQR) age at first assessment was 28 (19 to 41) months. PHIV children had lower age‐relevant Z scores for weight, height and head circumference compared to the PHEU group (p < 0.05).The prevalence of overall GDI was 18% (95% CI 11 to 27) and 32% (95% CI 20 to 47) in PHEU and PHIV children respectively (p = 0.06). In subgroup analysis, 22% (95% CI 9 to 42) of early ART PHIV children and 44% (95% CI 23 to 66) of standard ART PHIV children had overall GDI. There was a higher rate of GDI in standard ART PHIV children (p = 0.01), but not in the early ART group (p = 0.62) when compared with PHEU children. The standard ART PHIV group demonstrated lower typical developmental pattern than both the early ART PHIV group and the PHEU group (57% vs. 77% vs. 82% respectively). Non‐attendance at nursery school was associated with changes in ELC score during study participation (adjusted coefficient −3.8; 95% CI −6.1 to −1.6, p = 0.001).ConclusionsPreschool children with HIV who initiated ART in the first three months of life had a similar rate of GDI as PHEU children. Lack of nursery school attendance predicted poor developmental trajectory outcomes among PHIV children.
Synthesis, Characterization, and Computational Study of New Ferrocene‐Based Schiff Bases as Potential Nonionic Surfactants
Authors: Ali Shazaib , Badshah Amin , Hussain Hamid , Fatima Saira , Shah Aamir Hassan , Shah Afzal , Saifullah Salim , Shah Muhammad Raza 
Published: April 2019

AbstractFerrocene‐based nonionic surfactants were synthesized by reacting ferrocenylcarboxyaldehyde with different long‐chain amines. Nonionic surfactants were characterized using Fourier transform infrared spectra (FT‐IR), 1HNMR, and 13CNMR spectroscopy. The ferrocene‐based surfactants were characterized using ultraviolet (UV)–visible spectroscopy and surface tension measurements to determine the critical micelle concentration (CMC). The CMC values indicate high aggregation ability of the synthesized surfactants in ethanol. Dominance of their hydrophilic character was ensured from hydrophilic–lipophilic balance in the 10–15 range. Voltammetric response of all surfactants showed well‐defined and stable redox signals. Computational studies further revealed their physicochemical characteristics. Results of the study confirm the multifunctionality of the surfactants and suggest utilization in various fields.
A Thermally Stable Polyamine/Unsaturated Fatty Acid System: Gelation Behaviors and Application
Authors: Zhang Li , Li Qin‐Tang , Hu Run‐Tao , Luan Ling‐Yu 
Published: April 2019

AbstractThe gelation behavior of diethylenetriamine (DETA) and oleic acid (OLA) with different molar ratios in water was investigated. The gels, which were composed of lamellar phase and vesicles, were characterized using small‐angle X‐ray scattering (SAXS) and freeze‐fracture transmission electron microscopy (FF‐TEM). The responsive rheological properties were also investigated. Our results show that lamellar gels and rodlike micelles were formed successively with the increase of the DETA/OLA molar ratio. The lamellar gels exhibiting high thermal stability can be obtained in a wide range of polyamine/unsaturated fatty acid molar ratios. The mechanism of lamellar gel formation was explained by the packing parameter and the noncovalent interactions between the building blocks. Moreover, gel–sol transition can be triggered by tuning pH and ionic strength. This system has a good emulsification property, and no obvious nanoemulsion droplet coarsening is observed upon dilution after 30 days.