bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focally amplified lncRNA on chromosome 1 regulates apoptosis of esophageal cancer cells via DRP1 and mitochondrial dynamics
Authors: Liu Tao , Wang Zhi , Zhou Riqiang , Liang Wulin 
Published: November 2018

AbstractLong noncoding RNAs (lncRNAs), a family of noncoding RNA transcripts with a length of <200 nucleotides (nts), have been associated with the pathological development of various types of carcinogenesis. Focally amplified lncRNA on chromosome 1 (FAL1) is a recently identified lncRNA. In the current study, we aimed to investigate the physiological function of FAL1 in esophageal squamous cell carcinoma (ESCC). Our findings demonstrate that FAL1 was associated with esophageal cancer cell survival by regulating mitochondrial fission. First, we found that the expression of the mitochondrial fission protein dynamin‐related protein 1 (DRP1) was significantly reduced, but the expression of the mitochondrial fusion protein mitofusin 1 (Mfn1) was increased in ESCC tissues and esophageal cancer cell lines as compared with adjacent normal tissues and a normal esophagus epithelial cell line. In addition, we found that reduced expression of DRP1 in the esophageal cancer cell lines KYSE450 and EC9706 cells was associated with increased expression of FAL1. Inhibition of FAL1 promoted mitochondrial fission and mitochondrial dysfunction in KYSE450 and EC9706 cells mediated by DRP1. Silencing of DRP1 abolished FAL1‐induced apoptosis through a mitochondrial‐dependent pathway. Our findings suggest that FAL1/DRP1 could be a therapeutic target for the treatment of ESCC. © 2018 IUBMB Life, 71(1):254–260, 2019
Regulatory role of vitamin E in the immune system and inflammation
Authors: Lewis Erin Diane , Meydani Simin Nikbin , Wu Dayong 
Published: November 2018

AbstractVitamin E, a potent lipid‐soluble antioxidant, found in higher concentration in immune cells compared to other cells in blood, is one of the most effective nutrients known to modulate immune function. Vitamin E deficiency has been demonstrated to impair normal functions of the immune system in animals and humans, which can be corrected by vitamin E repletion. Although deficiency is rare, vitamin E supplementation above current dietary recommendations has been shown to enhance the function of the immune system and reduce risk of infection, particularly in older individuals. The mechanisms responsible for the effect of vitamin E on the immune system and inflammation have been explored in cell‐based, pre‐clinical and clinical intervention studies. Vitamin E modulates T cell function through directly impacting T cell membrane integrity, signal transduction, and cell division, and also indirectly by affecting inflammatory mediators generated from other immune cells. Modulation of immune function by vitamin E has clinical relevance as it affects host susceptibility to infectious diseases such as respiratory infections, in addition to allergic diseases such as asthma. Studies examining the role of vitamin E in the immune system have typically focused on α‐tocopherol; however, emerging evidence suggests that other forms of vitamin E, including other tocopherols as well as tocotrienols, may also have potent immunomodulatory functions. Future research should continue to identify and confirm the optimal doses for individuals at different life stage, health condition, nutritional status, and genetic heterogeneity. Future research should also characterize the effects of non‐α‐alpha‐tocopherol vitamin E on immune cell function as well as their potential clinical application. © 2018 IUBMB Life, 71(4):487–494, 2019
Cigarette smoke extract may induce lysosomal storage disease‐like adverse health effects
Authors: Park Eun‐Jung , Park Yoo‐Jin , Lee Sang Jin , Yoon Cheolho , Lee Kyuhong 
Published: November 2018

AbstractCigarette smoke is known to be associated with the incidence of a variety of pulmonary diseases, and alveolar macrophages are a key player in the defense mechanism against inhalable toxicants. Herein, we have found that a hydrophilic fraction in smoke extracts from 3R4F reference cigarettes (CSE) contains high concentrations of volatile substances compared to cigarette smoke condensate (amphoteric fraction). We also identified the toxic mechanism of CSE using MH‐S, a mouse alveolar macrophage cell line. CSE decreased cell viability accompanying increased lactate dehydrogenase release. Additionally, mitochondrial volume and the potential increased along with enhanced expression of mitochondrial fusion proteins and decreased adenosine triphosphate production. Similarly, CSE clearly induced increase of catalase activity and intracellular calcium concentration and decrease of endoplasmic reticulum and lysosome volume at the highest dose. More interestingly, damaged organelles accumulated in the cytosol, and CSE‐containing particles specifically penetrated to mitochondria. Meanwhile, any significant change in autophagy related protein expression was not found in CSE‐treated cells. Subsequently, we evaluated the effects of CSE on secretion of inflammatory related cytokines and chemokines, considering the relationship between organelle damage and the disturbed immune response. Very importantly, we found that expression of innate and adaptive immunity related mediators is disrupted following CSE exposure. Taken together, we suggest that CSE may cause the accumulation of damaged organelles in the cytoplasm by impairing selective autophagic function. In addition, this accumulation is responsible for the inadequate ability of immune cells to repair the damage of lung tissue following exposure to CSE.
The use of cobalt chloride as a chemical hypoxia model
Authors: Muñoz‐Sánchez Jorge , Chánez‐Cárdenas María E. 
Published: November 2018

AbstractThe use of hypoxia models in cell culture has allowed the characterization of the hypoxia response at the cellular, biochemical and molecular levels. Although a decrease in oxygen concentration is the optimal hypoxia model, the problem faced by many researchers is access to a hypoxia chamber or a CO2 incubator with regulated oxygen levels, which is not possible in many laboratories. Several alternative models have been used to mimic hypoxia. One of the most commonly used models is cobalt chloride‐induced chemical hypoxia because it stabilizes hypoxia inducible factors 1α and 2α under normoxic conditions. This model has several advantages, and currently, there is a substantial amount of scattered information about how this model works. This review describes the characteristics of the model, as well as the biochemical and molecular bases that support it. The regulation of hypoxia inducible factors by oxygen and the role of CoCl2 are explained to understand the most accepted bases of the CoCl2‐induced hypoxia model. The different current hypotheses that explain the establishment of hypoxic conditions using CoCl2 are also described. Finally, based on the different observations reported in the literature, we provide a critical review about the scope and limitations of this widely used chemical hypoxia model to be informative to all researchers interested in the field.
Endothelin‐1 triggers human peritoneal mesothelial cells’ proliferation via ERK1/2‐Ets‐1 signaling pathway and contributes to endothelial cell angiogenesis
Authors: Zhu Nan , Gu Lijie , Jia Jieshuang , Wang Xuan , Wang Ling , Yang Man , Yuan Weijie 
Published: November 2018

AbstractBackgroundDysfunction of the peritoneum as a dialysis organ may result from progressive membrane injury on peritoneal dialysis (PD). It has been increasingly recognized that the human peritoneal mesothelial cells (HPMCs) play a key role in peritoneal membrane early injury. Recently, it has been reported that bioincompatible PD fluid with high concentrations of glucose and glucose degradation products, low pH, high osmolality, and peritonitis stimulates HPMCs to release endothelin‐1 (ET‐1). ET‐1 causes increased the release of vascular endothelial growth factor, which is important for tumor cell angiogenesis. We hypothesized that activating ET‐1 might predict injury of peritoneal membrane.MethodsHPMCs were isolated from normal omentum. ERK1/2 and Ets‐1 phosphorylation were measured by Western blot analysis. HPMC proliferation was detected by the bromodeoxyuridine (BrdU) assay. Capillary networks of tubes formed were photographed under a microscope, and five randomly selected fields from each well were analyzed for total capillary length by using Image J software.ResultsMEK‐1 blocker significantly abolished the ERK1/2 activation by ET‐1, which also triggered phosphorylation, thus activating the transcription factor Ets‐1 downstream from ERK1/2. ET‐1 was capable to induce HPMC proliferation, which could be attenuated by ET‐1 antagonists. Antibody and small interfering RNA mediated blockade of Ets‐1 had similar antiproliferative effects. Thus, ET‐1 specifically triggered HPMC proliferation via ERK1/2‐Ets‐1 signaling pathway. VEGF production and endothelial cell angiogenesis were significantly in response to conditioned medium from HPMCs treated with ET‐1.ConclusionsET‐1 triggered HPMC proliferation through the ERK1/2‐Ets‐1 signaling pathway and contributed to VEGF production and endothelial cell angiogenesis.
MicroRNA‐338‐3p inhibits tumor growth and metastasis in osteosarcoma cells by targeting RUNX2/CDK4 and inhibition of MAPK pathway
Authors: Jia Feng , Zhang Zhen , Zhang Xu 
Published: November 2018

AbstractOsteosarcoma (OS) is one of the most aggressive bone tumors. MicroRNAs (miRNAs) have been found to implicate in the pathogenesis of different types of cancers, including OS. This study aimed to explore the roles of miR‐338‐3p in OS and investigate the underlying mechanism. Human OS cell lines (MG‐63 and U2OS) and osteoblast (hFOB) cell line were used in the study. The expression levels of miR‐338‐3p, runt‐related transcription factor 2 (RUNX2) and cyclin‐dependent kinase 4 (CDK4) were altered by transient transfection and determined by quantitative real‐time polymerase chain reaction/Western blot analysis. Cell viability, colony numbers, migration, and invasion, and apoptotic cells were measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, colony formation assay, transwell assay, and flow cytometry assay, respectively. Dual luciferase reporter assay was performed to identify the target gene of miR‐338‐3p. Western blot assay was carried to measure the protein expression levels involved in cell apoptosis, migration, and mitogen‐activated protein kinases (MAPK) pathway. We found that the expression of miR‐338‐3p was downregulated in MG‐63 cell and U2OS cells, compared with hFOB cells. MiR‐338‐3p suppression significantly increased cell viability and colony numbers, promoted cell migration, and invasion, but suppressed cell apoptosis in MG‐63 and U2OS cells. Opposite results were observed in the miR‐338‐3p overexpression. Interestingly, RUNX2 and CDK4 were direct target genes of miR‐338‐3p. RUNX2 inhibition shared a similar effect of miR‐338‐3p mimic on MG‐63 cells. Furthermore, miR‐338‐3p inhibited the activation of MAPK pathway in MG‐63 cells. To conclude, these findings suggested that miR‐338‐3p functioned as a tumor suppressor in OS cells by targeting RUNX2 and CDK4, as well as inhibition of the MAPK pathway.
lncRNA nuclear‐enriched abundant transcript 1 promotes cell proliferation and invasion by targeting miR‐186‐5p/HIF‐1α in osteosarcoma
Authors: Tan Hongyu , Zhao Liang 
Published: November 2018

AbstractIncreasing evidence shows that the long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) plays important roles in tumor progression. However, the function and the underlying mechanism of NEAT1 in osteosarcoma (OS) remain unclear. In the present study, we found that NEAT1 expression was significantly upregulated in OS tissues and cell lines. High NEAT1 expression was closely associated with advanced clinicopathologic features and poor overall survival of patients with OS. Using in vitro function assay, we found that NEAT1 could promote the proliferation, invasion, and epithelial‐mesenchymal transition (EMT) process of OS cells. NEAT1 could also promote OS cell growth in vivo. In addition, our studies showed that miR‐186‐5p was a downstream target of NEAT1 in OS. Functionally, miR‐186‐5p suppressed the proliferation, invasion, and EMT process of OS cells. Furthermore, our data revealed that HIF‐1α was a downstream target of miR‐186‐5p and that NEAT1 could exert its tumor oncogenic roles on OS cells via the miR‐186‐5p/HIF‐1α axis. Taking our results together, we elucidated that the NEAT1/miR‐186‐5p/HIF‐1α axis might be a therapeutic approach for the treatment of OS.
Dual actions of the antioxidant chlorophyllin, a glutathione transferase P1‐1 inhibitor, in tumorigenesis and tumor progression
Authors: Ozcan Mehmet , Esendagli Gunes , Musdal Yaman , Canpinar Hande , Bacanlı Merve , Anlar Hatice Gul , Esendağlı‐Yılmaz Güldal , Beyramzadeh Mojtaba , Aksoy Yasemin 
Published: November 2018

AbstractGlutathione (GSH) and enzymes related to this antioxidant molecule are often overexpressed in tumor cells and may contribute to drug resistance. Blockade of glutathione transferases (GSTs) has been proposed to potentiate the efficacy of chemotherapeutic drugs in cancer. The aim of this study was to evaluate the effect of chlorophyllin that has antioxidant properties, and also interferes with the activity of GST P1‐1, on breast cancers in vitro and in vivo. The in vivo studies were conducted using an N‐methyl‐
N‐nitrosourea (MNU)‐induced chemical carcinogenesis model in laboratory rats. DNA damage, GST activity, and GSH levels were determined in liver and tumor tissues. Treatment with chlorophyllin increased the GSH levels in the liver and significantly decreased DNA damage in the blood, liver, and tumor tissues. Even though tumorigenesis was delayed in rats receiving chlorophyllin before MNU injections, once the tumors emerged, the progression of tumor appeared to be faster than in the animals that received the carcinogen only. Out of nine breast cell lines, GST P1‐1 expression was detected in MCF‐12A, MDA‐MB‐231, and HCC38. Concomitant incubation with chlorophyllin and docetaxel did not significantly affect cell proliferation and viability. Chlorophyllin displayed genoprotective effects that initially delayed tumorigenesis. However, once the tumors were established, it may act as a promoter that facilitates tumor growth, potentially by a mechanism independent of cell proliferation and viability. Our results underline the pros and cons of antioxidant treatment in cancer, even if it has a capacity to inhibit GST P1‐1.
Expression of circulating miR‐17, miR‐25, and miR‐133 in breast cancer patients
Authors: Hesari AmirReza , Azizian Mitra , Darabi Hassan , Nesaei Abolfazl , Hosseini Seyede Atefe , Salarinia Reza , Motaghi Amir Ali , Ghasemi Faezeh 
Published: November 2018

AbstractOne of the most lethal cancers among women is breast cancer. MicroRNAs (miRNAs) can be of great importance in the early detection of breast cancer. This study aimed to investigate some miRNAs in the serum of patients with breast cancer compared with the control group. Total RNA was extracted from the serum of patients with breast cancer and healthy volunteers. The expression levels of miRNAs and the genes were assessed using real‐time reverse transcriptase‐polymerase chain reaction with specific primers. Our data showed that miR‐25 and miR‐133 were downregulated, and miR‐17 was upregulated in patients with breast cancer. Upregulation of miR‐17 is related to the poor survival time and increased cell proliferation. The reduced expression of miR‐133 and miR‐25 is significantly associated with clinical stage, metastasis, and survival time of patients with breast cancer. Expressions of miRNAs miR‐17, miR‐25, and miR‐133 are altered in patients with clinical stage, metastasis, poor survival time.
The discovery of a novel eight‐mRNA‐lncRNA signature predicting survival of hepatocellular carcinoma patients
Authors: Shi Ye‐Min , Li Yan‐Yan , Lin Jia‐Yun , Zheng Lei , Zhu Yi‐Ming , Huang Jian 
Published: November 2018

AbstractIncreasing evidence indicates that the expressions of messenger RNAs (mRNAs) and long non‐coding RNAs (lncRNAs) undergo a frequent and aberrant change in carcinogenesis and cancer development. But some research was carried out on mRNA‐lncRNA signatures for prediction of hepatocellular carcinoma (HCC) prognosis. We aimed to establish an mRNA‐lncRNA signature to improve the ability to predict HCC patients’ survival. The subjects from the cancer genome atlas (TCGA) data set were randomly divided into two parts: training data set (n = 246) and testing data set (n = 124). Using computational methods, we selected eight gene signatures (five mRNAs and three lncRNAs) to generate the risk score model, which were significantly correlated with overall survival of patients with HCC in both training and testing data set. The signature had the ability to classify the patients in training data set into a high‐risk group and low‐risk group with significantly different overall survival (hazard ratio = 4.157, 95% confidence interval = 2.648‐6.526, P < 0.001). The prognostic value was further validated in testing data set and the entire data set. Further analysis revealed that this signature was independent of tumor stage. In addition, Gene Set Enrichment Analysis suggested that high risk score group was associated with cell proliferation and division related pathways. Finally, we developed a well‐performed nomogram integrating the prognostic signature and other clinical information to predict 3‐ and 5‐year overall survival. In conclusion, the prognostic mRNAs and lncRNAs identified in our study indicate their potential role in HCC biogenesis. The risk score model based on the mRNA‐lncRNA may be an efficient classification tool to evaluate the prognosis of patients’ with HCC.
The comparative study of the effects of Fe2O3 and TiO2 micro‐ and nanoparticles on oxidative states of lung and bone marrow tissues and colony stimulating factor secretion
Authors: Soltani Arash , Kahkhaie Kolsoum Rezaie , Haftcheshmeh Saeed Mohammadian , Jalali Nezhad Ahmad Ali , Akbar Boojar Masoud Mashhadi 
Published: November 2018

AbstractNowadays, increased use of nanomaterials in industry and biomedicine poses potential risks to human health and the environment. Studying their possible toxicological effects is therefore of great significance. The present investigation was designed to examine the status of oxidative stress induced by nanoparticles (NPs) of ferric oxide (Fe2O
3) and titanium oxide (TiO
2) with their micro‐sized counterpart on mouse lung and bone marrow–derived normal tissue cells. We assessed the induction of oxidative stress by measuring its indicators such as antioxidant scavenging activity of superoxide dismutase and catalase as well as malondialdehyde concentration. Moreover, colony formation of bone marrow cells was assayed following induction with colony stimulating factor (CSF) from lung cells. NPs had a more potent stimulatory effect on the oxidative stress status than their micron‐sized counterparts. In addition, the highest level of oxidative stress derived from TiO
2 NPs was observed in both tissue types. Cotreatment with NPs and the antioxidant α‐tocopherol reduced antioxidant activities and membrane lipid peroxidation (LPO) in the lung cells, but increased CSF‐induced colony formation activity of bone marrow cells, suggesting that oxidative stress may be the cause of the cytotoxic effects of NPs. It is concluded that free radicals generated following exposure to NPs resulted in signiﬁcant oxidative stress in mouse cells, indicated by increased LPO and antioxidant enzyme activity and decreased colony formation.
Identification of potentially critical genes in the development of heart failure after ST‐segment elevation myocardial infarction (STEMI)
Authors: Qian Cheng , Chang Danqi , Li Hang , Wang Yanggan 
Published: November 2018

AbstractHeart failure (HF) remains a common complication after acute ST‐segment elevation myocardial infarction (STEMI). Here, we aim to identify critical genes related to the developed HF in patients with STEMI using bioinformatics analysis. The microarray data of GSE59867, including peripheral blood samples from nine patients with post‐infarct HF and eight patients without post‐infarct HF, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non‐HF groups were screened by LIMMA package. Functional enrichment analyses of DEGs were conducted, followed by construction of a protein‐protein interaction (PPI) network. The dynamic messenger RNA (mRNA) level of the hub genes during the follow‐up was analyzed to further elucidate their role in HF development. A total of 58 upregulated and 75 downregulated DEGs were screen out. They were mainly enriched in biological processes about inflammatory response, extracellular matrix organization, response to cAMP, immune response, and positive regulation of cytosolic calcium ion concentration. Pathway analysis revealed that the DEGs were also involved in hematopoietic cell lineage, pathways in cancer, and extracellular matrix‐receptor interaction. In the PPI network consisting of 58 nodes and 72 interactions, CXCL8 (degree = 15), THBS1 (degree = 8), FOS (degree = 7), and ITGA2B (degree = 6) were identified as the hub genes. In the comparison of patients with and without post‐infarct HF, the mRNA level of these hub genes were all higher within 30 days but reached similar at 6 months after STEMI. In conclusion, CXCL8, THBS1, FOS, and ITGA2B may play important roles in the development of HF after acute STEMI.
How hsa‐miR‐495 performed in the tumorigenesis of pancreatic adenocarcinoma by bioinformatics analysis
Authors: Yang Yuemei , Wang Yanfeng , Liu Shizhong , Zhao Xiaoling , Jia Rujing , Xiao Yu , Zhang Ming , Li Xiaoou , Li Ji , Wang Wenze 
Published: November 2018

AbstractIntroductionPancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world for early metastasis, extensive invasion, and poor prognosis with a 5‐year survival rate less than 5%. However, the underlying mechanisms are poorly understood. Therefore, it is urgent to explore molecular markers for early diagnosis or therapy target to improve the outcome of PAAD.MethodsWe retrieved transcriptome data as well as clinical information from patients with PAAD in The Cancer Genome Altas (TCGA) database. Survival time associated microRNAs (miRNAs) and messenger RNAs (mRNAs) were initially identified, followed by enrichment analysis (Gene Ontology [GO] and pathway). The relationship between survival time associated miRNAs‐mRNAs was also investigated to discover putative transcriptional control mechanisms of PAAD. Finally, by consulting the literature and retrieving the database, we found that hsa‐miR‐495 might have played an important role in PAAD.ResultsIn total, 146 miRNAs from 378 miRNAs and 580 mRNA from 17 100 mRNA, including 328 risk mRNA and 252 protective mRNA, were found to be associated with the survival time of PAAD. Eight hundred eighty‐eight mRNA‐miRNA pairs were related to the survival time of PAAD, involving in 755 mRNAs and 35 miRNAs. We chose 13 miRNAs predicted by target gene in the miRanda database for further research. Among these 13 miRNAs, hsa‐miR‐495 was identified as a good biomarker. Through GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the significantly enriched pathways involved in focal adhesion, Staphylococcus aureus infection, and Intestinal immune network for immunoglobulin A production. And four target genes and 87 pathways of the hsa‐miR‐495 were enriched in PAAD. Interestingly, we found hsa‐miR‐495 with a low expression having a poor overall survival and significantly different recurrence rate within 5 years.ConclusionHsa‐miR‐495 and its target genes may serve as a prognostic and predictive marker in PAAD. Further research on the function of the hsa‐miR‐495 and its target genes in the KEGG pathway may provide references for treatment of PAAD.