bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of lncRNA snaR is correlated with progression and predicts poor survival of laryngeal squamous cell carcinoma
Authors: Liang Kun , Yang Ying , Zha Dingjun , Yue Bo , Qiu Jianhua , Zhang Changming 
Published: December 2018

AbstractLong noncoding RNAs (lncRNA) snaR is a characterized oncogenic lncRNA in triple negative breast cancer and ovarian cancer, while its role in other human diseases is unknown. In the present study, we found that plasma levels of snaR were upregulated in patients with laryngeal squamous cell carcinoma (LSCC) than in healthy controls. Plasma levels of snaR increased with increase in AJCC stages. Follow‐up study showed that high plasma levels of snaR were correlated with poor overall survival. Plasma levels of snaR were positively correlated with transforming growth factor beta (TGF‐β1) in patients with LSCC but not in healthy controls. Overexpression of snaR resulted in upregulation of TGF‐β1 in cells of human LSCC cell lines, while exogenous TGF‐β1 treatment showed no significant effect on snaR expression. snaR overexpression and exogenous TGF‐β1 treatment promoted LSCC cell proliferation, migration, and invasion. In addition, TGF‐β inhibitor partially reduced the enhancing effects of snaR overexpression on LSCC cell proliferation, migration, and invasion. Therefore, overexpression of lncRNA snaR is correlated with progression and predicts poor survival of LSCC and the mechanism of its actions is likely related to TGF‐β1.
MicroRNA‐543 promotes ovariectomy‐induced osteoporosis through inhibition of AKT/p38 MAPK signaling pathway by targeting YAF2
Authors: Li Xiang , Ning Lei , Zhao Xiangde , Wan Shuanglin 
Published: December 2018

AbstractThe present study aimed to determine the roles of miRNA‐543 in osteoporosis in rats induced by ovariectomy. The osteoporosis rat model was established by ovariectomy induction. MiRNA‐543 expression in osteoblasts was measured by quantitative real‐time polymerase chain reaction. The cell proliferation and apoptosis were measured by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and flow cytometry assays, respectively. Western blot analysis was conducted to examine the expression of YAF‐2 and AKT signaling. TargetScan analysis and dual‐luciferase reporter assay were performed to determine the target gene of miRNA‐543. MiRNA‐543 was significantly upregulated in osteoporosis rat model. Overexpression of miRNA‐543 significantly suppressed cell growth and promoted apoptosis in osteoblasts, whereas downregulation of miRNA‐543 significantly enhanced cell growth and inhibited apoptosis. MiRNA‐543 upregulation significantly inhibited YAF‐2 expression and suppressed the phosphorylation and expression of AKT and p38 mitogen‐activated protein kinases (MAPK) in osteoblasts. Furthermore, YAF‐2 knockdown enhanced the effects of miRNA‐543 on apoptosis in osteoblasts. AKT inhibitor MK2206 and p38 MAPK inhibitor SB203580 also enhanced the effects of miRNA‐543 on apoptosis in osteoblasts. Our findings revealed that inhibition of miRNA‐543 could protect osteoblasts against ovariectomy‐induced osteoporosis through AKT/p38 MAPK signaling pathway by targeting YAF2.
Integrative analyses of genes associated with idiopathic pulmonary fibrosis
Authors: Wang Huimei , Xie Qiqi , Ou‐Yang Wen , Zhang Mingwei 
Published: December 2018

AbstractIdiopathic pulmonary fibrosis (IPF), characterized by irreversible scarring and progressive destruction of the lung tissue, is one of the most common types of idiopathic interstitial pneumonia worldwide. However, there are no reliable candidates for curative therapies. Hence, elucidation of the mechanisms of IPF genesis and exploration of potential biomarkers and prognostic indicators are essential for accurate diagnosis and treatment of IPF. Recently, efficient microarray and bioinformatics analyses have promoted an understanding of the molecular mechanisms of disease occurrence and development, which is necessary to explore genetic alternations and identify potential diagnostic biomarkers. However, high false‐positive rates results have been observed based on single microarray datasets. In the current study, we performed a comprehensive analysis of the differential expression, biological functions, and interactions of IPF‐related genes. Three publicly available microarray datasets including 54 IPF samples and 34 normal samples were integrated by performing gene set enrichment analysis and analyzing differentially expressed genes (DEGs). Our results identified 350 DEGs genetically associated with IPF. Gene ontology analyses revealed that the changes in the modules were mostly enriched in the positive regulation of smooth muscle cell proliferation, positive regulation of inflammatory responses, and the extracellular space. Kyoto encyclopedia of genes and genomes enrichment analysis of DEGs revealed that IPF involves the TNF signaling pathway, NOD‐like receptor signaling pathway, and PPAR signaling pathway. To identify key genes related to IPF in the protein‐protein interaction network, 20 hub genes were screened out with highest scores. Our results provided a framework for developing new pathological molecular networks related to specific diseases in silico.
Clinical aspects of circulating miRNA‐335 in breast cancer patients: A prospective study
Authors: Swellam Menha , Mahmoud Magda Sayed , Hashim Maha , Hassan Naglaa M , Sobeih Mohamed Emam , Nageeb Amira M 
Published: December 2018

AbstractBackgroundThe impact of aberrant expression of miRNAs, small noncoding RNAs of 19 to 23 nucleotide, has been reported in different types of cancer, such as breast cancer. Authors aim to investigate the role of circulating miRNA‐335 as a diagnostic and prognostic marker for breast cancer.Materials and MethodsmiRNA‐335 expression was measured in primary breast cancer patients (n = 106), patients with benign breast lesion (n = 49) and healthy individuals as control (n = 40) using quantitative real‐time polymerase chain reaction and its diagnostic efficacy, relation with clinicopathological factors, and disease‐free survival (DFS) and overall survival (OS) were assessed.ResultsA significant decrease in miRNA‐335 expression was reported in patients with breast cancer as compared to the other two investigated groups. The positivity rate for miRNA were related to adverse clinical features of primary breast cancer as high histological grading (X2 = 7.72, P = 0.016), presence of metastasis to lymph node (X2 = 21.8, P < 0.001), large tumor size (X2 = 6.41, P = 0.041), and hormonal status (P < 0.001). miRNA‐335 mean rank level was significantly different among breast cancer subtypes and its level was inferior in triple negative breast cancer. Worse DFS (X2 = 7.76, P = 0.005) and OS (X2 = 9.3, P = 0.002) were reported with decreased miRNA‐335 level.ConclusionAssessment of circulating miRNA expression level is a promising minimal invasive marker for diagnosis and prediction of breast cancer prognosis with significant discrepancies among molecular breast cancer subtypes.
Association of the human aryl hydrocarbon receptor repressor (AhRR)‐c.565C>G transversion with male infertility: A case‐control study from Iran
Authors: Mohammad‐Hasani Azadeh , Hosseinzadeh Colagar Abasalt , Fallah Ali 
Published: December 2018

AbstractDioxins (eg, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin/TCDD), as environmental endocrine disruptors and toxic carcinogens, can affect male reproductive health. The influence of dioxins is mediated via the aryl hydrocarbon receptor (AhR) pathway and its repressor (AhRR). In this study, we investigated the association of AhRR‐c.565C>G transversion polymorphism with male infertility. In a hospital‐based case‐control study, 221 semen samples (111 infertile and 110 healthy controls) based on World Health Organization guidelines were collected from in vitro fertilization centers of Babol, Iran. The AhRR‐c.565C>G (rs2292596) polymorphism was genotyped using a polymerase chain reaction‐restriction fragment length polymorphism analysis. The difference in the allele frequency of AhRR‐c.565C>G transversion polymorphism did not reach a significant level. The genotype frequency was statistically significantly different between fertile and infertile men. We found that polymorphism rs2292596 (Pro185Ala) was statistically significantly associated with the risk of male infertility. In addition, the statistical difference became more significant when the frequency was compared between the Pro/Pro genotype and the Pro/Ala plus Ala/Ala genotype. The 185 Pro wild‐type alleles of AhRR may be associated with the risk of male infertility. The proallele also may diminish inhibition of AhR‐mediated signaling of exposure to environmental pollutants.
Total circulating cell‐free miRNA in plasma as a predictive biomarker of the thyroid diseases
Authors: Caglar Ozge , Cayir Akin 
Published: December 2018

AbstractBackgroundThyroid cancer is a common endocrine cancer. Great progress has been made in resolving its molecular mechanisms in recent years. The molecular changes observed in thyroid cancer can be used as biomarkers for diagnostic, prognostic and therapeutic purposes. MicroRNAs (miRNAs) are important components in biological and metabolic pathways, such as developmental stages, signal transduction, cell maintenance, and differentiation. Hence, their malfunctioning can expose humans to malignancies. miRNA expressions have been shown to be dysregulated in different tumor types, like thyroid cancer, and may cause tumor initiation and progression.In previous studies, only cancer has been studied, and miRNA has been detected from the tissues in all the studies performed. In this study, we have focused on thyroid diseases such as bening nodules and Hashimoto's disease, which might be the cause of thyroid cancer, and have carried out miRNA tests in the blood samples taken from the arms thyroid patients.Material and methodThe present study was conducted on the blood samples of 100 thyroid patients. Of the 100 patients in our study, 33 consisted of patients with thyroiditis, while 37 patients were diagnosed with benign thyroid nodules and 30 patients had thyroid cancer. For the control group, 18 patients were included. The plasma samples were analyzed, and the total miRNA levels were determined.ResultsWe found that the ccf‐miRNA amount of benign patients is significantly lower than that of the controls. Similarly, the miRNA amount in the controls is significantly higher than that of the thyroiditis (P = 0.06) and the malign groups miRNA (P = 0.084). Although the present study has a low number of patients, the plasma samples could be used as a source of circulating miRNAs. In addition, the total miRNA of thyroid diseases could be used as a biomarker for different types of thyroid diseases. We could suggest, for future study, that specific miRNAs in bodily fluid might show specific properties to be used as biomarkers of thyroid diseases.
An in silico pharmacological approach toward the discovery of potent inhibitors to combat drug resistance HIV‐1 protease variants
Authors: Nayak Chirasmita , Chandra Ishwar , Singh Sanjeev Kumar 
Published: December 2018

AbstractProtease inhibitors (PIs) are crucial drugs in highly active antiretroviral therapy for human immunodeficiency virus‐1 (HIV‐1) infections. However, resistance owing to mutations challenge the long‐term efficacy in the medication of HIV‐1‐infected individuals. Lopinavir (LPV) and darunavir (DRV), two second‐generation drugs are the most potent among PIs, hustling the drug resistance when mutations occur in the active and nonactive site of the protease (PR). Herein, we strive for compounds that can stifle the function of wild‐type (WT) HIV‐1 PR along with four major single mutants (I54M, V82T, I84V, and L90M) instigating resistance to the PIs using in silico approach. Six common compounds are retrieved from six databases using combined pharmacophore‐based and structure‐based virtual screening methodology. LPV and DRV are docked and the binding free energy is calculated to set the cut‐off value for selecting compounds. Further, to gain insight into the stability of the complexes the molecular dynamics simulation (MDS) is carried out, which uncovers two lead molecules namely NCI‐524545 and ZINC12866729. Both the lead molecules connect with WT and mutant HIV‐1 PRs through strong and stable hydrogen bond interactions when compared with LPV and DRV throughout the trajectory analysis. Interestingly, NCI‐524545 and ZINC12866729 exhibit direct interactions with I50/50′ by replacing the conserved water molecule as evidenced by MDS, which indicates the credible potency of these compounds. Hence, we concluded that NCI‐524545 and ZINC12866729 have great puissant to restrain the role of drug resistance HIV‐1 PR variants, which can also show better activity through in vivo and in vitro conditions.
A benzoxazole derivative PO‐296 inhibits T lymphocyte proliferation by the JAK3/STAT5 signal pathway
Authors: Luo Xing‐yan , Zhou Hong , Wang Si‐yu , Xiong Jing , Mo Chun‐fen , Guo Hui‐jie , Wang Yan‐tang , Yang Shu‐xia , Li Li‐mei , Zou Qiang , Liu Yang 
Published: December 2018

AbstractImmunosuppressants have shown striking achievements in treating autoimmune diseases in recent years. It is urgent to develop more immunosuppressants to provide more options for patients. PO‐296 [2‐(6‐chlorobenzo[d]oxazol‐2‐yl)‐4,5,6,7‐tetrahydro‐2H‐indazol‐3‐ol] was identified as a novel benzoxazole derivative. We observed that it exhibits an obvious immunosuppressive activity to T lymphocytes. PO‐296 significantly inhibited the proliferation of activated human T lymphocyte without cytotoxicity. Moreover, PO‐296 did not affect the expression of cluster of differentiation (CD)‐25 or CD69 but induced T lymphocyte cycle arrest in the G0/G1 phase. Furthermore, PO‐296 inhibited interleukin (IL)‐6, IL‐17, and interferon gamma expression but had no effect on IL‐2, IL‐4, or IL‐10. Yet, importantly, PO‐296 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5), increased the phosphorylation of p70S6K, but did not affect the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/mitogen‐activated protein kinase pathway. In conclusion, these findings indicate that PO‐296 inhibits human activated T‐lymphocyte proliferation by affecting the janus kinase 3 (JAK3)/STAT5 pathway. PO‐296 possesses a potential lead compound for the design and development of new immunosuppressants for the treatment of autoimmune diseases.
Targeting of high mobility group A2 by small interfering RNA‐loaded nanoliposome‐induced apoptosis and migration inhibition in gastrointestinal cancer cells
Authors: Mohammadi Ali , Mansoori Behzad , Savadi Pouria , khaze Vahid , Minouei Mahsa , McMillan Nigel A. J. , Hallaj‐Nezhadi Somayeh , Baradaran Behzad 
Published: December 2018

AbstractBackgroundConsidering the complex nature of gastrointestinal cancer, different methods including surgery, radiotherapy, and chemotherapy are considered for the treatment. Novel strategies including silencing of oncogenes using safe delivery systems could be considered as a novel approach in colorectal cancer treatment. The aim of this study was to investigate the silencing effect of high mobility group A2 (HMGA2) small interfering RNA (siRNA)–loaded nanoliposomes on gastrointestinal cancers.MethodsThe siRNA‐lipoplexes were prepared using dioleoyl trimethylammonium propane (DOTAP)/cholesterol (Chol)/1, 2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine (DOPE) through the freeze‐drying of a monophase solution method. The size, polydispersity index (PDI), and zeta‐potential of nanoliposomes were determined using Zetasizer analyzer. The morphology of the nanoliposomes was determined by transmission electron microscopy (TEM). The agarose gel‐retardation assay was carried out to confirm the loading of siRNAs into liposome. The silencing of the HMGA2 in cancer cells was evaluated by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR). The effect of liposomes on cell cytotoxicity was studied by MTT assay. The inhibitory effect of siRNA‐loaded liposomes was evaluated by a wound‐healing assay. The apoptosis induction was investigated via the annexin V/propidium iodide assay.ResultsThe size, PDI, and zeta‐potential of the prepared liposomes were found to be 350 nm, 0.67, and 86.3 mV, respectively. They were spherical in shape and could efficiently associate with siRNA. The results of gene silencing showed that the optimum condition of HMGA2 silencing was 80 pmol HMGA2 and 24 hours after treatment in each cancer cell lines. MTT assays indicated that silencing of HMGA2 in optimal condition could reduce the viability of the cancer cells more than 60% in the three cell lines. The result of the apoptosis assay showed more than 50% of the cell deaths related to the apoptosis in all three cell lines. The gene expression evaluation confirmed that apoptosis was induced via the intrinsic pathway inducing both caspase‐3 and ‐9 expressions. Also, the reduction in Bcl2 expression confirmed the activation apoptosis pathway in the treated cancer cells. The wound‐healing assay showed the suppression of cancer cell migration after treatment with the prepared nanoliposomes.ConclusionThe results of this study showed the HMGA2 siRNA‐loaded nanoliposomes could be effective in the treatment of gastrointestinal cancers.
Smac mimetics as novel promising modulators of apoptosis in the treatment of breast cancer
Authors: Nikkhoo Afshin , Rostami Narges , Hojjat‐Farsangi Mohammad , Azizi Gholamreza , Yousefi Bahman , Ghalamfarsa Ghasem , Jadidi‐Niaragh Farhad 
Published: December 2018

AbstractBreast cancer is the most prevalent cancer in women. Despite improvements in treatment, the rate of breast cancer‐related deaths is still high, and this issue needs further, accurate investigations. Although several treatment options are available, none of them are efficient for complete remission, particularly in advanced stages of the disease. It is known that cancerous cells have dysregulated apoptosis‐related pathways, by which they can remain alive for a long time, expand freely, and escape from apoptosis‐inducing drugs or antitumor immune responses. Therefore, modulation of apoptosis resistance in cancer cells may be an efficient strategy to overcome current problems faced in the development of immunotherapeutic approaches for the treatment of breast cancer. The inhibitors of apoptosis protein (IAPs) are important targets for cancer therapy because it has been shown that these molecules are overexpressed and highly active in various cancer cells and suppress apoptosis process in malignant cells by blockage of caspase proteins. There is evidence of Smac mimetics efficacy as a single agent; however, recent studies have indicated the efficacy of current anticancer immunotherapeutic approaches when combined with Smac mimetics, which are potent inhibitors of IAPs and synthesized mimicking Smac/Diablo molecules. In this review, we are going to discuss the efficacy of treatment of breast cancer by Smac mimetics alone or in combination with other therapeutics.
Does blastomere removal alter the expression level of miR‐Let7a and its target genes following mouse embryo biopsy?
Authors: Naseri Fatemeh , Hosseini Sara , Ghaffari Novin Marefat , Hosseini Ahmad , Heidari Mohammad hasan , Salehi Mohammad 
Published: December 2018

AbstractEmbryo manipulations may cause the misexpression of various genes, most of which play critical roles in the regulation of implantation. This study aimed to evaluate the effects of embryo biopsy on the expression of miR‐Let‐7a and its gene targets including ErbB4, Tgf‐α, Itg‐αv, Itg β3 on the implantation of mouse embryo. Embryos were produced by in vitro fertilization followed by blastomere biopsy at the eight‐cell stage. The effects of blastomere removal on the expression of genes ErbB4, Tgf‐α, Itg αv, Itg β3, and miR‐Let‐7a as well as the alteration of the blastocyst cell number were compared in both biopsied and non‐biopsied groups. Finally, blastocyst attachment was assessed on culture dishes precoated with Fibronectin. The results revealed that there were no significant differences between the biopsied and non‐biopsied embryos with reference to the blastocyst formation rates, the average inner cell mass, trophectoderm cell number, and percentage of attachment of blastocysts (P > 0.05). The expression of ErbB4, Itg‐β3, Itg‐αv, TGF‐α transcripts, and miR‐Let‐7a in blastocysts biopsied embryos did not differ from the non‐biopsied blastocysts (P > 0.05). The results demonstrated that the preimplantation embryo development and attachment of biopsied embryos in vitro is not adversely affected by one blastomere biopsy at the eight‐cell stage embryo.
Identification of hub genes to regulate breast cancer metastasis to brain by bioinformatics analyses
Authors: Tang Dongyang , Zhao Xin , Zhang Li , Wang Zhiwei , Wang Cheng 
Published: December 2018

AbstractBreast cancer with metastasis especially brain metastasis represents a significant cause of morbidity and mortality in patients. In this study, we aimed to investigate the hub genes and potential molecular mechanism in brain metastasis breast cancer. Expression profiles of the genes were extracted from the Gene Expression Omnibus (GEO) database. GO and KEGG pathway enrichment analyses were conducted at Database for Annotation, Visualization, and Integrated Discovery. Protein‐protein interaction (PPI) network was established by STRING database constructed by Cytoscape software. Hub genes were identified by the molecular complex detection (MCODE) plugin and the CytoHubba plugin. The transcription factor (TF) that regulates the expression of hub genes was analyzed using the NetworkAnalyst algorithm. Kaplan‐Meier curve was used to analyze the effects of hub genes on overall survival. Two GEO databases (GSE100534 and GSE52604) were downloaded from GEO databases. A total of 102 overlapped genes were identified, and the top five KEGG pathways enriched were pathways in cancer, HTLV‐I infection, focal adhesion, ECM‐receptor interaction, and protein digestion and absorption. By combing the results of MCODE and CytoHubba, a total of 10 hub genes were selected. Kaplan‐Meier curve showed that ANLN, BUB1, TTK, and SKA3 were closely associated with the overall survival of breast cancer patients. TF analysis results showed that E2F4, KDM5B, and MYC were crucial regulators for these four hub genes. The current study based on the GEO database provided novel understanding regarding the mechanism of breast cancer metastasis to brain and may provide novel therapeutic targets.
Prenatal sonographic diagnosis of Harlequin ichthyosis
Authors: Brandão Pedro , Seco Sandra , Loureiro Teresa , Ramalho Carla 
Published: December 2018

AbstractHarlequin ichthyosis is the most severe form of autosomal recessive congenital ichthyoses. So far, there are only a few reports of prenatal diagnosis in the literature, as prenatal sonographic features are quite subtle. We report a case of prenatal diagnosis of Harlequin ichthyosis on third‐trimester sonographic examination in a consanguineous couple with no history of the disease and describe its characteristic sonographic features.