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Experimental Cell Research

Sai Han, Ying Wang, Xuejiao Shi, Liju Zong, Lu Liu, Juan Zhang, Qiuhong Qian, Jing Jin, Yana Ma, Baoxia Cui, Xingsheng Yang, Beihua Kong, Youzhong Zhang
Although persistent human papilloma virus (HPV) infection exerts a crucial influence on cervical carcinogenesis, other factors are also involved in its development, such as intraepithelial lesions and cervical cancer. B7-H3 and B7-H4, which have been reported to be co-regulatory ligands in the B7 family, had been found to be overexpressed in cervical cancer and correlated with adverse clinicopathological features and poor prognosis in our previous studies. In this study, we sought to explore the effects of B7-H3 and B7-H4 on the cervical microenvironment...
August 9, 2018: Experimental Cell Research
Yi Gao, Yichao Zhao, Ancai Yuan, Longwei Xu, Xian Huang, Yuanyuan Su, Lingchen Gao, Qingqi Ji, Jun Pu, Ben He
Myocardial ischemia/reperfusion (MI/R) injury induces excessive cellular apoptosis and contributes significantly to final infarct size. We previously demonstrated that a nuclear receptor, Farnesoid X receptor (FXR), plays a crucial role in mediating myocardial apoptosis. The FXR functions are regulated by post translational modifications (PTM). However, whether the proapoptotic effect of FXR in MI/R injury is regulated by PTM remains unclear. Here, we aimed to study the effect of SUMOylation, a PTM involved in the pathogenesis of MI/R injury per se, on the proapoptotic effect of FXR in MI/R injury...
August 8, 2018: Experimental Cell Research
Wenjin Sun, Bing Xiao, Aijun Jia, Lulu Qiu, Qingping Zeng, Da Liu, Yu Yuan, Jingsi Jia, Xiufeng Zhang, Xudong Xiang
T helper 17 (Th17) cells has proven to be crucial in the pathogenesis of severe asthma. Although it is known that Suppressor of cytokine signaling 3 (SOCS3) is involved in differentiation of Th17 cells but, how it affects severe asthma is uncertain. Since previous studies indicated that Methtyl-CpG binding domain protein 2 (MBD2) null mice was deficient in Th17 cell differentiation, the aim of the present study was to understand how MBD2 interacts with SOCS3 to regulate Th17 cell differentiation in severe asthma...
August 8, 2018: Experimental Cell Research
Siyang Feng, Jianxue Zhai, Di Lu, Jie Lin, Xiaoying Dong, Xiguang Liu, Hua Wu, Anja C Roden, Giovanni Brandi, Simona Tavolari, Andrea Bille, Kaican Cai
Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines...
August 8, 2018: Experimental Cell Research
Ruth A Mitchell, Rodney B Luwor, Antony W Burgess
Research on the epidermal growth factor (EGF) family and the family of receptors (EGFR) has progressed rapidly in recent times. New crystal structures of the ectodomains with different ligands, the activation of the kinase domain through oligomerisation and the use of fluorescence techniques have revealed profound conformational changes on ligand binding. The control of cell signaling from the EGFR-family is complex, with heterodimerisation, ligand affinity and signaling cross-talk influencing cellular outcomes...
August 8, 2018: Experimental Cell Research
Markus Dietrich, Muhammad Salman Malik, Filip Nikolaysen, Marianne Skeie, Espen Stang
Overexpression of ErbB2 is frequent in cancer and understanding the mechanisms which regulate its expression is important. ErbB2 is considered endocytosis resistant. It has no identified ligand, but upon heterodimerization it is a potent mediator of proliferative signaling. A recent study established a role for protein kinase C (PKC) in internalization and recycling of ErbB2. We have now further investigated the molecular mechanisms involved in PKC-mediated downregulation of ErbB2. We confirm that PMA-induced PKC activation causes ErbB2 internalization, but while the Hsp90 inhibitor 17-AAG induced ErbB2 degradation, PMA had no such effect...
August 8, 2018: Experimental Cell Research
Yue Wang, Quan Liu, Yi Huan, Rongcui Li, Caina Li, Sujuan Sun, Nan Guo, Miaomiao Yang, Shuainan Liu, Zhufang Shen
Recently, SIRT5 was reported to be a predominant desuccinylase and demalonylase in mitochondria. Ablation of SIRT5 enhances the systemic succinylation and malonylation of mitochondrial proteins, including various metabolic enzymes; however, its function in pancreatic β cells has not yet been clarified. In this study, we evaluated the effects of SIRT5 overexpression on glucolipotoxicity-induced apoptosis in β cell lines. Full-length SIRT5, which preferentially targeted to mitochondria and partially to the nucleus and cytoplasm, was overexpressed in NIT-1 cells...
August 8, 2018: Experimental Cell Research
Mtakai Ngara, Mia Palmkvist, Sven Sagasser, Daisy Hjelmqvist, Åsa K Björklund, Mats Wahlgren, Johan Ankarklev, Rickard Sandberg
The malaria parasite has a complex lifecycle, including several events of differentiation and stage progression, while actively evading immunity in both its mosquito and human hosts. Important parasite gene expression and regulation during these events remain hidden in rare populations of cells. Here, we combine a capillary-based platform for cell isolation with single-cell RNA-sequencing to transcriptionally profile 165 single infected red blood cells (iRBCs) during the intra-erythrocyte developmental cycle (IDC)...
August 7, 2018: Experimental Cell Research
Yuzhen Xiong, Shang Wu, Huajun Yu, Jun Wu, Yajun Wang, Huimin Li, Hui Huang, Haitao Zhang
miRNAs regulate gene expression and enable clinicians to distinguish between benign and malignant tissues in cancers. PH domain leucine-rich repeat-containing protein phosphatase 1 (PHLPP1) is known to be a tumour suppressor. A lentiviral overexpression system was used to stably express miR-190, leading to the enhancement of hepatocellular carcinoma (HCC) proliferation and metastasis as a result of inhibited PHLPP1 expression. The results showed that stable miR-190 expression increased the expression of EMT-related proteins (Snail and TCF8/ZEB1) as well as the phosphorylation of Akt at Ser473 and the expression of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1)...
August 6, 2018: Experimental Cell Research
Yumiko Azuma, Takahiko Tokuda, Yukie Kushimura, Itaru Yamamoto, Ikuko Mizuta, Toshiki Mizuno, Masanori Nakagawa, Morio Ueyama, Yoshitaka Nagai, Yasushi Iwasaki, Mari Yoshida, Duojia Pan, Hideki Yoshida, Masamitsu Yamaguchi
Mutations in the Fused in Sarcoma (FUS) gene have been identified in familial ALS in human. Drosophila contains a single ortholog of human FUS called Cabeza (Caz). We previously established Drosophila models of ALS targeted to Caz, which developed the locomotive dysfunction and caused anatomical defects in presynaptic terminals of motoneurons. Accumulating evidence suggests that ALS and cancer share defects in many cellular processes. The Hippo pathway was originally discovered in Drosophila and plays a role as a tumor suppressor in mammals...
August 6, 2018: Experimental Cell Research
Maria Eriksdotter, Manuel Navarro-Oviedo, Sumonto Mitra, Lars Wahlberg, Bengt Linderoth, Lars O Tjernberg, Homira Behbahani
Alzheimer's disease (AD) is characterized by early degeneration of cholinergic neurons and decreased levels of nerve growth factor (NGF). Thus, increasing the NGF levels by for instance encapsulated cell bio-delivery (ECB) is a potential treatment strategy. The results from our previous first-in-human studies on ECB of NGF to the basal forebrain cholinergic neurons were promising, but indicated some variability of long-term viability of the encapsulated cells and associated reduced NGF-release. Here we studied the effect of amyloid beta-peptides (Aβ), interleukin 1-beta (IL-1β), and CSF from AD, Lewy body dementia (LBD) or subjective cognitive impairment (SCI) patients on the NGF overproducing cell line NGC-0295...
August 6, 2018: Experimental Cell Research
Bei Tong, Vasiliki Pantazopoulou, Elinn Johansson, Alexander Pietras
Tumor hypoxia is associated with several features of aggressive glioma growth, including migration, invasion, and stemness. Most of the cellular adaptation to hypoxia is mediated by the hypoxia-inducible factors HIF-1α and HIF-2α, but regulation of these factors by both oxygen-dependent and -independent mechanisms in brain tumors is only partially understood. Here, we show that the p75 neurotrophin receptor (p75NTR ) is stabilized at hypoxia in murine glioma in vivo, as well as in primary human glioma cultures in vitro...
August 6, 2018: Experimental Cell Research
Jingjing Jin, Zhan Zhang, Haowen Wang, Yu Zhan, Gang Li, Han Yang, Zhenghua Fei, Yunsheng Xu, Wenfeng Li
One of the major causes of death in colorectal cancer (CRC) is invasion and metastasis. Better understanding of the molecular mechanism of CRC invasion and metastasis is essential in developing effective cancer therapies. Cooperative effect of CXCR3 and CXCR4 plays a crucial role in regulating CRC invasion. In present study, we discovered that CRC cells expressing higher levels of CXCR3 and CXCR4 were more invasive. Additionally, CXCR3 formed heteromers with CXCR4 and retained CXCR4 on cell surface. CXCR3 knockdown reduced surface CXCR4 expression and partially inhibited CRC cell invasion...
August 6, 2018: Experimental Cell Research
Otto Väyrynen, Markku Piippo, Hannaleena Jämsä, Tuomas Väisänen, Carlos E B de Almeida, Tuula Salo, Sotiris Missailidis, Maija Risteli
Chemoradiation is an established approach in the treatment of advanced oral tongue squamous cell carcinoma (OTSCC), but therapy may cause severe side-effects due to signal interchanges between carcinoma and the tumour microenvironment (TME). In this study, we examined the potential use of our human 3D myoma disc and Myogel models in in vitro chemoradiation studies by analysing the effects of ionizing radiation (IR) and the combined effect of heparanase I (HPSE1) inhibitors and IR on OTSCC cell proliferation, invasion and MMP-2 and -9 production...
August 4, 2018: Experimental Cell Research
Rümeyza Bascetin, Lyvia Blay, Sabrina Kellouche, Franck Carreiras, Cédric Picot, Mélanie Briand, Rémy Agniel, Olivier Gallet, Charlotte Vendrely, Johanne Leroy-Dudal
Fibronectin (Fn) is an extracellular matrices (ECM) multifunctional glycoprotein essential for regulating cells behaviors. Within ECM, Fn is found as polymerized fibrils. Apart from fibrils, Fn could also form other kind of supramolecular assemblies such as aggregates. To gain insight into the impact of Fn aggregates on cell behavior, we generated several Fn oligomeric assemblies. These assemblies displayed various amyloid-like properties but were not cytotoxic. In presence of the more amyloid-like structured assemblies of Fn, the cell ECM networks were altered and the cell shapes shifted toward extended mesenchymal morphologies...
August 1, 2018: Experimental Cell Research
Qian Cao, Chen-Xia Juan, Dao-Qi Zhang, Jia He, Yi-Zhi Cao, Asfia Banu Pasha, Jin-Ya Wang, Hai-Xiao Qi, Sheng Li, Rui Jin, Guo-Ping Zhou
Orosomucoid 1-like protein 3 (ORMDL3) is an asthma candidate gene associated with virus-triggered recurrent wheeze. Stimulator of interferon gene (STING) controls TLR-independent cytosolic responses to viruses. However, the association of STING with ORMDL3 is unclear. Here, we have shown that ORMDL3 expression shows a linear correlation with STING in recurrent wheeze patients. In elucidating the molecular mechanisms of the ORMDL3-STING relationship, we found that STING promoted the transcriptional activity of ORMDL3, which was significantly associated with increased levels of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 6 (STAT6)...
August 1, 2018: Experimental Cell Research
Xin Jin, Yasen Aimaiti, Zixin Chen, Wei Wang, Dewei Li
Hepatic stellate cells (HSCs) are activated by transforming growth factor (TGF)-β1 and function as mesenchymal cells in liver regeneration. Activated HSCs also have proangiogenic ability in vivo. In this study, knockin of the TGF-β1 gene caused mHSCs to transform into myofibroblasts (MFs) highly expressing Jagged1 and vascular endothelial growth factor A (VEGFA). These MFs promoted formation of capillary-like structures by human umbilical vein endothelial cells (HUVECs) in vitro, which was much reduced after blocking TGF-β1 signaling...
July 31, 2018: Experimental Cell Research
Liuqi Yang, Zhengling Shang, Shiqi Long, Nianxue Wang, Ge Shan, Ruya Zhang
Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells lose their cell-cell contacts resulting in the formation of mesenchymal cells with migratory properties. Increasing evidence indicate EMT plays a key role in the invasion, metastasis and therapeutic resistance of cancer and maintenance of the phenotype of cancer stem cells (CSCs), which makes the prognosis of patients worse. The progression of cancer from epithelial tissue towards a malignant phenotype is driven by multiple factors that remodel the tissue architecture...
July 31, 2018: Experimental Cell Research
Katherine V Clark-Knowles, Danielle Dewar-Darch, Karen E Jardine, Josée Coulombe, Manijeh Daneshmand, Xiaohong He, Michael W McBurney
SIRT1 is a protein deacetylase with a broad range of biological functions, many of which are known to be important in carcinogenesis, however much of the literature regarding the role of SIRT1 in cancer remains conflicting. In this study we assessed the effect of SIRT1 on the initiation and progression of thymic T cell lymphomas. We employed mouse strains in which SIRT1 activity was absent or could be reversibly modulated in conjunction with thymic lymphoma induction using either the N-nitroso-N-methylurea (NMU) carcinogenesis or the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) transgene...
July 27, 2018: Experimental Cell Research
Kirstine Overgaard Nielsen, Kari Stougaard Jacobsen, Aashiq Hussain Mirza, Thilde Nordmann Winther, Joachim Størling, Dieter Glebe, Flemming Pociot, Birthe Hogh
Chronic hepatitis B (CHB) infection increases the risk of developing severe liver disease including cirrhosis and hepatocellular carcinoma (HCC). As microRNAs may modulate host - virus interactions, we here investigated if hepatitis B virus (HBV) infection modulate microRNA expression using an in vitro HepG2 cell model system with inducible HBV replication. We found that HBV replication was associated with upregulation of miR-192-5p, miR-194-5p and miR-215-5p, of which miR-192-5p and miR-215-5p have identical seed sequences...
July 27, 2018: Experimental Cell Research
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