bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rs217727 polymorphism in H19 promotes cell apoptosis by regulating the expressions of H19 and the activation of its downstream signaling pathway
Authors: Ge Lili , Wang Qinglei , Hu Shengnan , Yang Xiaoang 
Published: October 2018

AbstractBackgroundThe objective of the current study was to explore the role of H19 rs217727 polymorphism in the control of hepatocellular carcinoma (HCC).MethodThe Student's t test, Cox regression, and Kaplan–Meier analyses were used to clarify whether the H19 rs217727 polymorphism played an important role in the development of HCC. Real‐time polymerase chain reaction (PCR) and western‐blot analysis were carried out to measure the levels of H19, microRNA (miR)‐675, FAS‐associated death domain (FADD), caspase‐8, and caspase‐3 among H19 CC, CT, and TT groups, as well as in cells transfected with H19/si‐H19, or miR‐675 mimic/inhibitor. The MTT assay, colony formation assay, and flow cytometry assay were performed to detect the effect of H19/miR‐675 on cell viability, cell colony formation, and cell apoptosis.ResultT allele of H19 rs217727 polymorphism apparently increased the survival rate of patients with HCC. Meanwhile, H19 enhanced miR‐675 expression but reduced the mRNA and protein levels of FADD, caspase‐3, and caspase‐8. The T allele of H19 rs217727 polymorphism apparently increased the apoptotic rate of HCC cells. Furthermore, FADD was a virtual target gene of miR‐675 with a potential “hit” located in the 3′‐untranslated region (UTR) of FADD, whereas H19 inhibited FADD expression via increasing the expression of miR‐675. Moreover, H19 upregulated the expression of miR‐675 whereas reducing the expression of FADD, caspase‐3, and caspase‐8. Finally, H19 and miR‐675 promoted cell proliferation and cell colony formation but repressed cell apoptosis.ConclusionIn summary, the above findings demonstrated that the polymorphism of rs217727 in H19 was associated with HCC via the H19/miR‐675/FADD/caspase‐8/caspase‐3/apoptosis signaling pathway.
Antibodies reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein, in sera from children
Authors: Mazzoni Elisa , Frontini Francesca , Rotondo John Charles , Zanotta Nunzia , Fioravanti Arianna , Minelli Francesca , Torreggiani Elena , Campisciano Giuseppina , Marcuzzi Annalisa , Guerra Giovanni , Tommasini Alberto , Touzé Antoine , Martini Fernanda , Tognon Mauro , Comar Manola 
Published: October 2018

AbstractRecent data indicate that the Simian virus 40 (SV40) infection appears to be transmitted in humans independently from early SV40‐contaminated antipolio vaccines. Serum antibodies against SV40 large T antigen (Tag) were analyzed in children/adolescents and young adults. To investigate antibodies reacting to SV40 Tag antigens, serum samples (
n = 812) from children and young adults were analyzed by indirect ELISAs using specific SV40 Tag mimotopes. Mimotopes were synthetic peptides corresponding to SV40 Tag epitopes. In sera (
n = 412) from healthy children up to 17 years old, IgG antibodies against SV40 Tag mimotopes reached an overall prevalence of 15%. IgM antibodies against SV40 Tag were detected in sera of children 6–8 months old confirming and extending the knowledge that SV40 seroconversion occurs early in life. In children/adolescents affected by different diseases (
n = 180) SV40 Tag had a prevalence of 18%, being the difference no significant compared to healthy subjects (
n = 220; 16%) of the same age. Our immunological data indicate that SV40 circulates in children and young adults, both in healthy conditions and affected by distinct diseases. The IgM detection in sera from healthy children suggests that the SV40 infection/seroconversion occurs early in life (>6 months). Our immunological data support the hypothesis that SV40, or a closely related still unknown polyomavirus, infects humans. The SV40 seroprevalence is lower than common polyomaviruses, such as BKPyV and JCPyV, and other new human polyomaviruses. In addition, our immunological surveillance indicates a lack of association between different diseases, considered herein, and SV40.
Mitochondrial dysfunction and inhibition of myoblast differentiation in mice with high‐fat‐diet‐induced pre‐diabetes
Authors: Xu Dengqiu , Jiang Zhenzhou , Sun Zeren , Wang Lu , Zhao Guolin , Hassan Hozeifa M. , Fan Sisi , Zhou Wang , Han Shuangshuang , Zhang Luyong , Wang Tao 
Published: October 2018

AbstractPre‐diabetes is characterized by impaired glucose tolerance (IGT) and/or impaired fasting glucose. Impairment of skeletal muscle function is closely associated with the progression of diabetes. However, the entire pathological characteristics and mechanisms of pre‐diabetes in skeletal muscle remain fully unknown. Here, we established a mouse model of pre‐diabetes, in which 6‐week‐old male C57BL6/J mice were fed either normal diet or high‐fat diet (HFD) for 8 or 16 weeks. Both non‐fasting and fasting glucose levels and the results of glucose and insulin tolerance tests showed that mice fed an 8‐week HFD developed pre‐diabetes with IGT; whereas mice fed a 16‐week HFD presented with impaired fasting glucose and impaired glucose tolerance (IFG‐IGT). Mice at both stages of pre‐diabetes displayed decreased numbers of mitochondria in skeletal muscle. Moreover, IFG‐IGT mice exhibited decreased mitochondrial membrane potential and ATP production in skeletal muscle and muscle degeneration characterized by a shift in muscle fibers from predominantly oxidative type I to glycolytic type II. Western blotting and histological analysis confirmed that myoblast differentiation was only inhibited in IFG‐IGT mice. For primary skeletal muscle satellite cells, inhibition of differentiation was observed in palmitic acid‐induced insulin resistance model. Moreover, enhanced myoblast differentiation increased glucose uptake and insulin sensitivity. These findings indicate that pre‐diabetes result in mitochondrial dysfunction and inhibition of myoblast differentiation in skeletal muscle. Therefore, interventions that enhance myoblast differentiation may improve insulin resistance of diabetes at the earlier stage.
Retracted: Suppression of microRNA‐342‐3p increases glutamate transporters and prevents dopaminergic neuron loss through activating the Wnt signaling pathway via p21‐activated kinase 1 in mice with Parkinson's disease
Authors: Wu Dong‐Mei , Wang Shan , Wen Xin , Han Xin‐Rui , Wang Yong‐Jian , Shen Min , Fan Shao‐Hua , Zhuang Juan , Zhang Zi‐Feng , Shan Qun , Li Meng‐Qiu , Hu Bin , Sun Chun‐Hui , Lu Jun , Chen Gui‐Quan , Zheng Yuan‐Lin 
Published: October 2018

AbstractDevelopment of effective therapeutic drugs for Parkinson's disease (PD) is of great importance. Aberrant microRNA (miRNA) expression has been identified in postmortem human PD brain samples, in vitro and in vivo PD models. However, the role of miR‐342‐3p in PD has been understudied. The study explores the effects of miR‐342‐3p on expression of glutamate (Glu) transporter, and dopaminergic neuron apoptosis and proliferation by targeting p21‐activated kinase 1 (PAK1) through the Wnt signaling pathway in PD mice. After establishment of PD mouse models, gain‐ or loss‐of‐function assay was performed to explore the functional role of miR‐342‐3p in PD. Number of apoptotic neurons and Glu concentration was then determined. Subsequently, PC12 cells were treated with miR‐342‐3p mimic, miR‐342‐3p inhibitor, dickkopf‐1 (DKK1), and miR‐342‐3p inhibitor + DKK1. The expression of miR‐342‐3p, PAK1, the Wnt signaling pathway‐related and apoptosis‐related genes, Glutamate transporter subtype 1 (GLT‐1), l‐glutamate/
l‐aspartate transporter (GLAST), tyrosine hydroxylase (TH) was measured. Also, cell viability and apoptosis were evaluated. PD mice exhibited increased miR‐342‐3p, while decreased expression of PAK1, GLT‐1, GLAST, TH, and the Wnt signaling pathway‐related and antiapoptosis genes. miR‐342‐3p downregulation could promote expression of PAK1, the Wnt signaling pathway‐related and antiapoptosis genes. GLT‐1, GLAST, and TH as well as cell viability, but reduce cell apoptosis rate. The results indicated that suppression of miR‐342‐3p improves expression of Glu transporter and promotes dopaminergic neuron proliferation while suppressing apoptosis through the Wnt signaling pathway by targeting PAK1 in mice with PD.
Novel pathways involved in cisplatin resistance identified by a proteomics approach in non‐small‐cell lung cancer cells
Authors: Milone Maria Rita , Lombardi Rita , Roca Maria Serena , Bruzzese Francesca , Addi Laura , Pucci Biagio , Budillon Alfredo 
Published: October 2018

AbstractAlthough platinum‐based chemotherapy remains the standard‐of‐care for most patients with advanced non‐small‐cell lung cancer (NSCLC), acquired resistance occurs frequently predicting poor prognosis. To examine the mechanisms underlying platinum resistance, we have generated and characterized by proteomic approach the resistant A549 CDDP‐resistant (CPr‐A549) and their parental A549 cells, identifying 15 proteins differentially expressed (13 upregulated and 2 downregulated in CPr‐A549). In details, we highlighted a coherent network of proteins clustering together and involved in altered protein folding and endoplasmic reticulum stress, correlated with epithelial to mesenchymal transition process and cancer stem cell markers, where vimentin played a hierarchical role, ultimately resulting in increased aggressive features. By using publicly available databases we showed that the modulated proteins could contribute to NSCLC carcinogenesis and correlate with NSCLC patients prognosis and survival probability, suggesting that they can be used as novel potential prognostic/predictive biomarkers or therapeutic targets to overcome platinum‐resistance.
LncRNA–CDC6 promotes breast cancer progression and function as ceRNA to target CDC6 by sponging microRNA‐215
Authors: Kong Xiaoli , Duan Yi , Sang Yuting , Li Yaming , Zhang Hanwen , Liang Yiran , Liu Ying , Zhang Ning , Yang Qifeng 
Published: October 2018

AbstractRapid proliferation and metastasis of breast cancers resulted in poor prognosis in clinic. Recent studies have proved that long noncoding RNAs (lncRNAs) were involved in tumor progression. In this study, we aimed to determine the roles and mechanisms of lncRNA–cell division cycle 6 (CDC6) in regulating proliferation and metastasis of breast cancer. Clinically, lncRNA–CDC6 was highly expressed in tumor tissues and was positively correlated with clinical stages of breast cancers. Functionally, the ectopic expression of lncRNA–CDC6 promoted proliferation via regulation of G1 phase checkpoint, and further promoting the migration capability. Moreover, lncRNA–CDC6 could function as competitive endogenous RNA (ceRNA) via directly sponging of microRNA‐215 (miR‐215), which further regulating the expression of CDC6. Taken together, our results proved that lncRNA–CDC6 could function as ceRNA and promote the proliferation and metastasis of breast cancer cells, which provided a novel prognostic marker for breast cancers in clinic.
Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis
Authors: Uddin Md. Sahab , Mamun Abdullah Al , Labu Zubair Khalid , Hidalgo‐Lanussa Oscar , Barreto George E. , Ashraf Ghulam Md 
Published: October 2018

AbstractAutophagy is a preserved cytoplasmic self‐degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy‐related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis.
Construction and functional characterization of a fully human anti‐CD19 chimeric antigen receptor (huCAR)‐expressing primary human T cells
Authors: Mirzaei Hamid Reza , Jamali Arezoo , Jafarzadeh Leila , Masoumi Elham , Alishah Khadijeh , Fallah Mehrjardi Keyvan , Emami Seyed Amir Hossein , Noorbakhsh Farshid , Till Brian G. , Hadjati Jamshid 
Published: October 2018

AbstractAlthough remarkable results have been attained by adoptively transferring T cells expressing fully murine and/or humanized anti‐CD19 chimeric antigen receptors (CARs) to treat B cell malignancies, evidence of human anti‐mouse immune responses against CARs provides a rationale for the development of less immunogenic CARs. By developing a fully human CAR (huCAR), these human anti‐mouse immune responses are likely eliminated. This, perhaps, not only increases the persistence of anti‐CD19 CAR T cells—thereby reducing the risk of tumor relapse—but also facilitates administration of multiple, temporally separated doses of CAR T cells to the same recipient. To these ends, we have designed and constructed a second‐generation fully human anti‐CD19 CAR (or huCAR19) containing a fully human single‐chain variable fragment (ScFv) fused with a CD8a hinge, a 4‐1BB transmembrane domain and intracellular T cell signaling domains of 4‐1BB and CD3z. T cells expressing this CAR specifically recognized and lysed CD19+ target cells produced cytokines and proliferated in vitro. Moreover, cell volume data revealed that our huCAR construct cannot induce antigen‐independent tonic signaling in the absence of cognate antigen. Considering our results, our anti‐CD19 huCAR may overcome issues of transgene immunogenicity that plague trials utilizing CARs containing mouse‐derived ScFvs. These results suggest that this huCAR19 be safely and effectively applied for adaptive T cell immunotherapy in clinical practice.
Generation of functional human pancreatic organoids by transplants of embryonic stem cell derivatives in a 3D‐printed tissue trapper
Authors: Soltanian Anahita , Ghezelayagh Zahra , Mazidi Zahra , Halvaei Majid , Mardpour Soura , Ashtiani Mohammad Kazemi , Hajizadeh‐Saffar Ensiyeh , Tahamtani Yaser , Baharvand Hossein 
Published: October 2018

AbstractOrganoids can be regarded as a beneficial tool for discovery of new therapeutics for diabetes and/or maturation of pancreatic progenitors (PP) towards β cells. Here, we devised a strategy to enhance maturation of PP by assembly of three‐dimensional (3D) pancreatic organoids (PO) containing human embryonic stem (ES) cell derivatives including ES‐derived pancreatic duodenal homeobox 1 (PDX1)
+ early PP, mesenchymal stem cells, and endothelial cells at an optimized cell ratio, on Matrigel. The PO was placed in a 3D‐printed tissue trapper and heterotopically implanted into the peritoneal cavity of immunodeficient mice where it remained for 90 days. Our results indicated that, in contrast to corresponding early PP transplants, 3D PO developed more vascularization as indicated by greater area and number of vessels, a higher number of insulin‐positive cells and improvement of human C‐peptide secretions. Based on our findings, PO‐derived β cells could be considered a novel strategy to study human β‐cell development, novel therapeutics, and regenerative medicine for diabetes.
Loss of HACE1 promotes colorectal cancer cell migration via upregulation of YAP1
Authors: Zhou Zhen , Zhang Hong‐Sheng , Zhang Zhong‐Guo , Sun Hong‐Liang , Liu Hui‐Yun , Gou Xiao‐Meng , Yu Xiao‐Ying , Huang Ying‐Hui 
Published: October 2018

AbstractColorectal cancer (CRC) is the third‐leading cause of cancer mortality worldwide. HACE1 function as a tumor‐suppressor gene and is downregulated in several kinds of cancers. However, the distribution and clinical significance of HACE1 in CRC is still not clarified. In this study, we found that the HACE1 expression is greatly downregulated in CRC tissues and cell lines. Moreover, the HACE1 expression was significantly associated with inhibition of CRC cell proliferation, metastasis, and invasion. HACE1 inhibited epithelial–mesenchymal transition in CRC cells. Furthermore, we found that
HACE1 altered the protein expression of the Hippo pathway by downregulation of YAP1. HACE1 suppresses the invasive ability of CRC cells by negatively regulating the YAP1 pathway. Our data indicates that HACE1 directly targets YAP1 and induces downregulation of YAP1, thereby increasing the activity of the Hippo pathway. In summary, these findings demonstrated that HACE1–YAP1 axis had an important part in the CRC development and progression.
H19/miR‐148a/USP4 axis facilitates liver fibrosis by enhancing TGF‐β signaling in both hepatic stellate cells and hepatocytes
Authors: Zhu Jie , Luo Zhongguang , Pan Yida , Zheng Wanwei , Li Wenshuai , Zhang Ziqiang , Xiong Panpan , Xu Diannan , Du Meiling , Wang Bangting , Yu Jianghong , Zhang Jun , Liu Jie 
Published: October 2018

AbstractLiver fibrosis is a wound‐healing response represented by excessive extracellular matrix deposition. Activation of hepatic stellate cell (HSC) is the critical cellular basis for hepatic fibrogenesis, whereas hepatocyte undergoes epithelial‐mesenchymal transition (EMT) which is also involved in chronic liver injury. Long noncoding RNA H19 has been found to be associated with cholestatic liver fibrosis lately. However, the role of H19 in liver fibrosis remains largely to be elucidated. In this study, we found that the expression of H19 was significantly upregulated in the liver tissue of CCl4‐induced mice, a toxicant‐induced liver fibrogenesis model. Overexpression of H19 significantly aggravated activation of HSC and EMT of hepatocyte both by stimulating transforming growth factor‐β (TGF‐β) pathway. In terms of mechanism, H19 functioned as a competing endogenous RNA to sponge miR‐148a and subsequently sustained the level of ubiquitin‐specific protease 4 (USP4), which was an identified target of miR‐148a and was able to stabilize TGF‐β receptor I. In conclusion, our findings revealed a novel H19/miR‐148a/USP4 axis which promoted liver fibrosis via TGF‐β pathway in both HSC and hepatocyte, indicating that H19 could become a promising target for the treatment of liver fibrosis.
miR‐15a‐5p suppresses inflammation and fibrosis of peritoneal mesothelial cells induced by peritoneal dialysis via targeting VEGFA
Authors: Shang Jin , He Qianxin , Chen Ying , Yu Dahai , Sun Lulu , Cheng Genyang , Liu Dong , Xiao Jing , Zhao Zhanzheng 
Published: October 2018

AbstractLong‐term peritoneal dialysis (PD) often ends up with ultrafiltration failure (UFF) which is partially caused by persistent inflammation and fibrosis of peritoneal tissues. However, the mechanism is still unclear. In the current study, the peritoneum from UFF patients demonstrated inflammation and fibrosis which were positively related to the expression of vascular endothelial growth factor A (VEGFA). The in vitro model using human peritoneal mesothelial cells (HPMCs) stimulated by high glucose or advanced glycation end (AGE) product showed consistent changes of inflammation, fibrosis, and VEGFA. What's more, we showed that VEGFA was an instigator of inflammation and fibrosis. Several microRNAs (miRNAs) have been reported to regulate expression of VEGFA elsewhere. Five of them were selected to test the expression in the peritoneum of patients with PD. Results suggested that miR‐15a‐5p was the most significantly downregulated one. Also, in high glucose or AGE product‐stimulated HPMCs, miR‐15a‐5p decreased. When miRNA mimic was used to restore the expression of miR‐15a‐5p, high glucose‐induced VEGFA was repressed. The predicted binding site between these two molecules was confirmed by the dual‐luciferase assay. Restoration of miR‐15a‐5p restrained inflammation and fibrosis of HPMCs. TGF‐β1/Smad2 was shown to be the downstream signaling pathway and their activity was regulated by miR‐15a‐5p/VEGFA. In conclusion, our current study demonstrates that miR‐15a‐5p acts as a regulator of VEGFA mRNA and the following inflammation and fibrosis in peritoneal mesothelial cells. The miR‐15a‐5p/VEGFA pathway may be a potential target for preventing ultrafiltration failure in patients with PD.
The transcriptome profiles and methylation status revealed the potential cancer‐related lncRNAs in patients with cervical cancer
Authors: Yuan Li‐Yun , Qin Xiaomin , Li Lin , Zhou Jinting , Zhou Min , Li Xianxian , Xu Ying , Wang Xiao‐Jun , Xing Hui 
Published: October 2018

AbstractCervical cancer continues to be a major public health problem. Although long noncoding RNAs (lncRNAs) were involved in the initiation and progression of cancer, few studies focus on the lncRNAs in the cervical cancer. Here, we systematically studied the clinical information, transcriptome profiling, and methylation array data of cervical squamous cell carcinoma and endocervical adenocarcinoma that retrieved from genomic data commons (GDC). Compared with protein‐coding genes, the expression levels of pseudogenes and lncRNAs were much lower. A total of 190 differentially expressed lncRNAs and 2,326 protein‐coding genes were identified. Meanwhile, 269 differentially methylation regions (DMRs), where 16 lncRNAs were located, were figured out. Only one lncRNA, LINC00592, which was located in the DMRs, was also found differentially expressed. Several transcriptional regulation genes, such as ZNF20, ZNF441, ZNF573, and TMF1, were highly correlated with the expression of LINC00592, which illustrated its possible function on the transcription. Two microRNAs, which were both associated with tumor progression, can bind to LINC00592. Moreover, LINC00592 were also differentially expressed in other tumors. We proposed, with the help of various databases, that LINC00592 is a potential cancer‐related lncRNA in cervical cancer and might activate the cancer progression through the regulation of transcription or structural integrity.