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Thiago Verano-Braga, Vladimir Gorshkov, Sune Munthe, Mia D Sørensen, Bjarne W Kristensen, Frank Kjeldsen
Glioblastoma (GBM) is a highly aggressive brain cancer with poor prognosis and low survival rate. Invasive cancer stem-like cells (CSCs) are responsible for tumor recurrence because they escape current treatments. Our main goal was to study the proteome of three GBM subpopulations to identify key molecules behind GBM cell phenotypes and potential cell markers for migrating cells. We used SuperQuant-an enhanced quantitative proteome approach-to increase proteome coverage. We found 148 proteins differentially regulated in migrating CSCs and 199 proteins differentially regulated in differentiated cells...
February 6, 2018: Oncotarget
Oksana Voloshanenko, Uwe Schwartz, Dominique Kranz, Benedikt Rauscher, Michael Linnebacher, Iris Augustin, Michael Boutros
Wnt signaling is an evolutionarily conserved signaling route required for development and homeostasis. While canonical, β-catenin-dependent Wnt signaling is well studied and has been linked to many forms of cancer, much less is known about the role of non-canonical, β-catenin-independent Wnt signaling. Here, we aimed at identifying a β-catenin-independent Wnt target gene signature in order to understand the functional significance of non-canonical signaling in colon cancer cells. Gene expression profiling was performed after silencing of key components of Wnt signaling pathway and an iterative signature algorithm was applied to predict pathway-dependent gene signatures...
February 16, 2018: Scientific Reports
M V Shitova, A A Kochnev, O G Dolnikova, N V Kryukova, T V Malinina, A A Pereverzev
We study 117 Pacific walrus samples from three rookeries within the western part of Chukchi Sea (Cape Vankarem, Cape Serdtse-Kamen, and Kolyuchin Island). We analyze the variability of nuclear (20 microsatellite loci) and mitochondrial DNA (three fragments). Two microsatellite loci which are described as microsatellites for the first time are used in this study: repeated sequences within introns of Coro1c and Plod2 genes. A high degree of genetic diversity is demonstrated for both nuclear and mitochondrial markers compared to Atlantic walrus...
February 2017: Genetika
Baoyi Zhu, Mari Ekman, Daniel Svensson, Jessica Lindvall, Bengt-Olof Nilsson, Bengt Uvelius, Karl Swärd
Bladder denervation and bladder outlet obstruction are urological conditions that cause bladder growth. Transcriptomic surveys in outlet obstruction have identified differentially expressed genes, but similar studies following denervation have not been done. This was addressed using a rat model in which the pelvic ganglia were cryo-ablated followed by bladder microarray analyses. At 10 days following denervation, bladder weight had increased 5.6-fold and 2890 mRNAs and 135 miRNAs were differentially expressed...
January 10, 2018: American Journal of Physiology. Renal Physiology
Gabriela Ferraz Leal, Gen Nishimura, Ulrika Voss, Débora Romeo Bertola, Eva Åström, Johan Svensson, Guilherme Lopes Yamamoto, Anna Hammarsjö, Eva Horemuzova, Nikos Papadiogannakis, Erik Iwarsson, Giedre Grigelioniene, Emma Tham
Osteogenesis imperfecta (OI) is a strikingly heterogeneous group of disorders with a broad range of phenotypic variations. It is also one of the differential diagnoses in bent bone dysplasias along with campomelic dysplasia and thanatophoric dysplasia and can usually be distinguished by decreased bone mineralization and bone fractures. Bent bone dysplasias also include syndromes such as kyphomelic dysplasia (MIM:211350) and mesomelic dysplasia Kozlowski-Reardon (MIM249710), both of which have been under debate regarding whether or not they are a real entity or simply a phenotypic manifestation of another dysplasia including OI...
November 27, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Fang Lv, Xiaojie Xu, Yuwen Song, Lujiao Li, Asan, Jian Wang, Huanming Yang, Ou Wang, Yan Jiang, Weibo Xia, Xiaoping Xing, Mei Li
Bruck syndrome is a rare autosomal recessive form of osteogenesis imperfecta (OI), which is mainly characterized by joint contractures and recurrent fragility fractures. Mutations in FKBP10 and PLOD2 were identified as the underlying genetic defects of Bruck syndrome. Here we investigated the phenotypes and the pathogenic mutations of three unrelated Chinese patients with Bruck syndrome. Clinical fractures, bone mineral density (BMD), bone turnover biomarkers, and skeletal images were evaluated in detail. The pathogenic mutations were identified by targeted next-generation sequencing and subsequently confirmed by Sanger sequencing and cosegregation analysis...
March 2018: Calcified Tissue International
Hongzhi Du, Yulong Chen, Xiaoying Hou, Yue Huang, Xiaohui Wei, Xiaowen Yu, Shuyun Feng, Yao Wu, Meixiao Zhan, Xin Shi, Sensen Lin, Ligong Lu, Shengtao Yuan, Li Sun
In multiple types of tumors, fibrotic collagen is regarded as the 'highway' for cancer cell migration, which is mainly modified by lysyl hydroxylase 2 (PLOD2). The previous findings have demonstrated that the expression of PLOD2 was regulated by multiple factors, including HIF-1α, TGF-β and microRNA-26a/b. Although PLOD2 was confirmed to be related to poor prognosis in lung adenocarcinoma, the regulatory mechanism and function of PLOD2 in human lung adenocarcinoma is poorly understood. On the other hand, upregulation or hyperactivation of epidermal growth factor receptor is considered as a prognostic marker in many cancers, especially in non-small-cell lung cancer (NSCLC)...
October 26, 2017: Cell Death & Disease
A M Sashi Papu John, Sourav Kundu, Sathnur Pushpakumar, Maura Fordham, Gregory Weber, Manas Mukhopadhyay, Utpal Sen
The relationship between hydrogen sulfide (H2S), microRNAs (miRs), matrix metalloproteinases (MMPs) and poly-ADP-ribose-polymerase-1 (PARP-1) in diabetic kidney remodeling remains mostly obscured. We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibrosis in diabetes kidney, and whether H2S ameliorates fibrosis. Wild type, diabetic Akita mice as well as mouse glomerular endothelial cells (MGECs) were used as experimental models, and GYY4137 as H2S donor. In diabetic mice, plasma H2S levels were decreased while ROS and expression of its modulator (ROMO1) were increased...
September 7, 2017: Scientific Reports
Linwei Li, Wenyu Wang, Xiaoyan Li, Tianhui Gao
Esophageal cancer-related gene 4 (ECRG4) is a tumor suppressor gene associated with the prognosis of esophageal squamous-cell carcinoma (ESCC). Studies have reported that ECRG4 effectively inhibits the proliferation, migration and invasion of ESCC cells. In the current study, ectopic expression of ECRG4 significantly induced ESCC cell apoptosis. To further understand the molecular profile of ECRG4 overexpression in ESCC cells, tandem mass tag (TMT) labeling followed by LC-MS/MS analysis was applied on samples from ECRG4 overexpressed cells and control cells...
2017: American Journal of Translational Research
Marco Maccarana, René B Svensson, Anki Knutsson, Antonis Giannopoulos, Mea Pelkonen, MaryAnn Weis, David Eyre, Matthew Warman, Sebastian Kalamajski
The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs). Not all SLRPs' effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigated SLRPs is asporin. Here we describe the successful generation of an Aspn-/- mouse model and the investigation of the Aspn-/- skin phenotype. Functionally, Aspn-/- mice had an increased skin mechanical toughness, although there were no structural changes present on histology or immunohistochemistry...
2017: PloS One
Simona G Codreanu, Megan D Hoeksema, Robbert J C Slebos, Lisa J Zimmerman, S M Jamshedur Rahman, Ming Li, Sheau-Chiann Chen, Heidi Chen, Rosana Eisenberg, Daniel C Liebler, Pierre P Massion
We hypothesized that distinct protein expression features of benign and malignant pulmonary nodules may reveal novel candidate biomarkers for the early detection of lung cancer. We performed proteome profiling by liquid chromatography-tandem mass spectrometry to characterize 34 resected benign lung nodules, 24 untreated lung adenocarcinomas (ADCs), and biopsies of bronchial epithelium. Group comparisons identified 65 proteins that differentiate nodules from ADCs and normal bronchial epithelium and 66 proteins that differentiate ADCs from nodules and normal bronchial epithelium...
August 8, 2017: Journal of Proteome Research
Y Liu, Asan, D Ma, F Lv, X Xu, J Wang, W Xia, Y Jiang, O Wang, X Xing, W Yu, J Wang, J Sun, L Song, Y Zhu, H Yang, J Wang, M Li
The achievement of more accurate diagnosis would greatly benefit the management of patients with osteogenesis imperfecta (OI). In this study, we present the largest OI sample in China as screened by next generation sequencing. In particular, we successfully identified 81 variants, which included 45 novel variants. We further did a genotype-phenotype analysis, which helps make a better understanding of OI. INTRODUCTION: This study aims to reveal the gene mutation spectrum and the genotype-phenotype relationship among Chinese OI patients by next generation sequencing (NGS)...
July 19, 2017: Osteoporosis International
Feifei Xu, Jialu Zhang, Guolin Hu, Lei Liu, Weijiang Liang
BACKGROUND: Intra-tumoral hypoxia and increases in extracellular level of transforming growth factor β1 (TGF-β1), which are common findings in cancer, are associated with an increased risk of metastasis and mortality. Moreover, metastasis is the leading cause of death of patients with cervical cancer. PLOD2 is an intracellular enzyme required for the biogenesis of collagen and its expression can be induced by hypoxia and TGF-β1. Specifically, PLOD2 is up-regulated in several types of cancer, including cervical cancer, and is associated with cancer metastasis...
2017: Cancer Cell International
Yangyang Xu, Lin Zhang, Yuzhen Wei, Xin Zhang, Ran Xu, Mingzhi Han, Bing Huang, Anjing Chen, Wenjie Li, Qing Zhang, Gang Li, Jian Wang, Peng Zhao, Xingang Li
Poor prognosis of glioblastoma multiforme is strongly associated with the ability of tumor cells to invade the brain parenchyma, which is believed to be the major factor responsible for glioblastoma recurrence. Therefore, identifying the molecular mechanisms driving invasion may lead to the development of improved therapies for glioblastoma patients. Here, we investigated the role of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), an enzyme catalyzing collagen cross-linking, in the biology of glioblastoma invasion...
April 4, 2017: Oncotarget
Hongzhi Du, Mao Pang, Xiaoying Hou, Shengtao Yuan, Li Sun
Collagen is not only the most abundant protein providing the scaffold for assembly of the extracellular matrix (ECM), but also considered to be the "highway" for cancer cell migration and invasion depending on the different collagen organizations. The accumulation of stabilized collagen is enhanced by different covalent collagen cross-links, lysyl hydroxylases 2 (encoded by the PLOD2 gene) is the key enzyme mediating the formation of the stabilized collagen cross-link. Interestingly, PLOD2 is overexpressed in different cancers and closely related to a poor prognosis...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ye Song, Shihao Zheng, Jizhou Wang, Hao Long, Luxiong Fang, Gang Wang, Zhiyong Li, Tianshi Que, Yi Liu, Yilei Li, Xi'an Zhang, Weiyi Fang, Songtao Qi
Gliomas are the most common form of malignant primary brain tumors with poor 5-year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and molecular mechanism of PLOD2 in glioma have not been reported yet. In this study, PLOD2 was found to be frequently up-regulated in glioma and could serve as an independent prognostic marker to identify patients with poor clinical outcome. Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma cells in vitro and in vivo...
June 27, 2017: Oncotarget
Yulong Chen, Masahiko Terajima, Priyam Banerjee, Houfu Guo, Xin Liu, Jiang Yu, Mitsuo Yamauchi, Jonathan M Kurie
Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and -wild-type murine embryonic fibroblasts...
April 5, 2017: Scientific Reports
Emily B Lurier, Donald Dalton, Will Dampier, Pichai Raman, Sina Nassiri, Nicole M Ferraro, Ramakrishan Rajagopalan, Mahdi Sarmady, Kara L Spiller
Alternatively activated "M2" macrophages are believed to function during late stages of wound healing, behaving in an anti-inflammatory manner to mediate the resolution of the pro-inflammatory response caused by "M1" macrophages. However, the differences between two main subtypes of M2 macrophages, namely interleukin-4 (IL-4)-stimulated "M2a" macrophages and IL-10-stimulated "M2c" macrophages, are not well understood. M2a macrophages are characterized by their ability to inhibit inflammation and contribute to the stabilization of angiogenesis...
July 2017: Immunobiology
Belal Neyazi, Levent Tanrikulu, Ludwig Wilkens, Christian Hartmann, Klaus-Peter Stein, Claudia A Dumitru, I Erol Sandalcioglu
BACKGROUND AND OBJECTIVE: Brain arteriovenous malformations (bAVM) are severe conditions that can cause severe neurologic deficits and mortality. The underlying cellular and molecular mechanisms associated with bAVM growth and rupture remain unclear. The objective of this study was to explore the potential role of PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2) in the pathophysiology of bAVM. METHODS: Expression and localization of PLOD2 were analyzed on tissue microarrays from patients with bAVM (n = 60) by immunohistochemistry...
June 2017: World Neurosurgery
Jose A Caparros-Martin, Mona S Aglan, Samia Temtamy, Ghada A Otaify, Maria Valencia, Julián Nevado, Elena Vallespin, Angela Del Pozo, Carmen Prior de Castro, Lucia Calatrava-Ferreras, Pilar Gutierrez, Ana M Bueno, Belen Sagastizabal, Encarna Guillen-Navarro, Maria Ballesta-Martinez, Vanesa Gonzalez, Sarenur Y Basaran, Ruksan Buyukoglan, Bilge Sarikepe, Cecilia Espinoza-Valdez, Francisco Cammarata-Scalisi, Victor Martinez-Glez, Karen E Heath, Pablo Lapunzina, Victor L Ruiz-Perez
BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations in COL1A1 or COL1A2 and show autosomal dominant inheritance, during the last years there has been an explosion in the number of genes responsible for both recessive and dominant forms of this condition. Herein, we have analyzed a cohort of patients with OI, all offspring of unaffected parents, to determine the spectrum of variants accounting for these cases...
January 2017: Molecular Genetics & Genomic Medicine
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