liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 25 of 25
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Borrebaeck, Carl
    Lund Univ, Sweden.
    Elander, Nils
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Gasslander, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jornsten, Rebecka
    Univ Gothenburg, Sweden; Chalmers Univ Technol, Sweden.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Karolinska Univ Hosp, Sweden; Dept Lab Med, Sweden.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Schäfer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Stenmarker, Margaretha
    Futurum Acad Hlth and Care, Sweden; Inst Clin Sci, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sysoev, Oleg
    Linköping University, Department of Computer and Information Science, The Division of Statistics and Machine Learning. Linköping University, Faculty of Arts and Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Digital twins to personalize medicine2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 12, no 1, article id 4Article in journal (Refereed)
    Abstract [en]

    Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.

  • 2.
    Bruhn, Sören
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Fang, Yu
    Guiyang Medical Coll, Peoples R China University of Gothenburg, Sweden .
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Konstantinell, Aelita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Kronke, Andrea
    Cenix BioScience GmbH, Germany .
    Sonnichsen, Birte
    Cenix BioScience GmbH, Germany .
    Bresnick, Anne
    Albert Einstein Coll Med, NY 10461 USA .
    Dulyaninova, Natalya
    Albert Einstein Coll Med, NY 10461 USA .
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhao, Yelin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Klingelhofer, Jorg
    University of Copenhagen, Denmark .
    Ambartsumian, Noona
    University of Copenhagen, Denmark .
    Beck, Mette K.
    Technical University of Denmark, Denmark .
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bona, Elsa
    Boras Hospital, Sweden .
    Xiang, Zou
    University of Gothenburg, Sweden .
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy2014In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 6, no 218Article in journal (Refereed)
    Abstract [en]

    The identification of diagnostic markers and therapeutic candidate genes in common diseases is complicated by the involvement of thousands of genes. We hypothesized that genes co-regulated with a key gene in allergy, IL13, would form a module that could help to identify candidate genes. We identified a T helper 2 (T(H)2) cell module by small interfering RNA-mediated knockdown of 25 putative IL13-regulating transcription factors followed by expression profiling. The module contained candidate genes whose diagnostic potential was supported by clinical studies. Functional studies of human TH2 cells as well as mouse models of allergy showed that deletion of one of the genes, S100A4, resulted in decreased signs of allergy including TH2 cell activation, humoral immunity, and infiltration of effector cells. Specifically, dendritic cells required S100A4 for activating T cells. Treatment with an anti-S100A4 antibody resulted in decreased signs of allergy in the mouse model as well as in allergen-challenged T cells from allergic patients. This strategy, which may be generally applicable to complex diseases, identified and validated an important diagnostic and therapeutic candidate gene in allergy.

  • 3.
    Bruhn, Sören
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Katzenellenbogen, Mark
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Krönke, Andrea
    Cenix BioScience GmbH, Dresden, Germany.
    Sönnichsen, Birte
    Cenix BioScience GmbH, Dresden, Germany.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Combining gene expression microarray- and cluster analysis with sequence-based predictions to identify regulators of IL-13 in allergy2012In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 60, no 3, p. 736-740Article in journal (Refereed)
    Abstract [en]

    The Th2 cytokine IL-13 plays a key role in allergy, by regulating IgE, airway hyper secretion, eosinophils and mast cells. In this study, we aimed to identify novel transcription factors (TFs) that potentially regulated IL-13. We analyzed Th2 polarized naïve T cells from four different blood donors with gene expression microarrays to find clusters of genes that were correlated or anti-correlated with IL13. These clusters were further filtered, by selecting genes that were functionally related. In these clusters, we identified three transcription factors (TFs) that were predicted to regulate the expression of IL13, namely CEBPB, E2F6 and AHR. siRNA mediated knockdowns of these TFs in naïve polarized T cells showed significant increases of IL13, following knockdown of CEBPB and E2F6, but not AHR. This suggested an inhibitory role of CEBPB and E2F6 in the regulation of IL13 and allergy. This was supported by analysis of E2F6, but not CEBPB, in allergen-challenged CD4+ T cells from six allergic patients and six healthy controls, which showed decreased expression of E2F6 in patients. In summary, our findings indicate an inhibitory role of E2F6 in the regulation of IL-13 and allergy. The analytical approach may be generally applicable to elucidate the complex regulatory patterns in Th2 cell polarization and allergy.

  • 4.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    James, A. Rani
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Liljenstrom, R.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Muraro, A.
    Padua University Hospital, Italy .
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    The Allergic Airway Inflammation Repository - a user-friendly, curated resource of mRNA expression levels in studies of allergic airways2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no 8, p. 1115-1117Article in journal (Refereed)
    Abstract [en]

    Public microarray databases allow analysis of expression levels of candidate genes in different contexts. However, finding relevant microarray data is complicated by the large number of available studies. We have compiled a user-friendly, open-access database of mRNA microarray experiments relevant to allergic airway inflammation, the Allergic Airway Inflammation Repository (AAIR, http://aair.cimed.ike.liu.se/). The aim is to allow allergy researchers to determine the expression profile of their genes of interest in multiple clinical data sets and several experimental systems quickly and intuitively. AAIR also provides quick links to other relevant information such as experimental protocols, related literature and raw data files.

  • 5.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    Div Psychiat and Rehabil and Diagnost, Sweden; Karolinska Univ Hosp Huddinge, Sweden; Karolinska Univ Hosp, Sweden.
    Schäfer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Olsen, Renate Slind
    Div Psychiat and Rehabil and Diagnost, Sweden; Karolinska Inst, Sweden.
    Stenmarker, Margaretha
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Dept Paediat, Region Jönköping County, Sweden.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    An algorithm-based meta-analysis of genome- and proteome-wide data identifies a combination of potential plasma biomarkers for colorectal cancer2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 15575Article in journal (Refereed)
    Abstract [en]

    Screening programs for colorectal cancer (CRC) often rely on detection of blood in stools, which is unspecific and leads to a large number of colonoscopies of healthy subjects. Painstaking research has led to the identification of a large number of different types of biomarkers, few of which are in general clinical use. Here, we searched for highly accurate combinations of biomarkers by meta-analyses of genome- and proteome-wide data from CRC tumors. We focused on secreted proteins identified by the Human Protein Atlas and used our recently described algorithms to find optimal combinations of proteins. We identified nine proteins, three of which had been previously identified as potential biomarkers for CRC, namely CEACAM5, LCN2 and TRIM28. The remaining proteins were PLOD1, MAD1L1, P4HA1, GNS, C12orf10 and P3H1. We analyzed these proteins in plasma from 80 patients with newly diagnosed CRC and 80 healthy controls. A combination of four of these proteins, TRIM28, PLOD1, CEACAM5 and P4HA1, separated a training set consisting of 90% patients and 90% of the controls with high accuracy, which was verified in a test set consisting of the remaining 10%. Further studies are warranted to test our algorithms and proteins for early CRC diagnosis.

  • 6.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Serra-Musach, Jordi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Aagesen, Jesper
    Reg Jonkoping Cty, Sweden.
    Arenas, Alex
    Univ Rovira and Virgili, Spain.
    Asking, Bengt
    Reg Jonkoping Cty, Sweden.
    Bengner, Malin
    Reg Jonkoping Cty, Sweden.
    Bjorkander, Janne
    Reg Jonkoping Cty, Sweden.
    Biggs, Sophie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hjortswang, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Köpsén, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Schafer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sonmez, Ceylan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Stjernman, Henrik
    Reg Jonkoping Cty, Sweden.
    Tjärnberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wu, Simon
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Shalek, Alex K.
    MIT, MA 02139 USA; Broad Inst MIT and Harvard, MA 02142 USA; Ragon Inst MGH MIT and Harvard, MA USA.
    Stenmarker, Margaretha
    Reg Jonkoping Cty, Sweden; Inst Clin Sci, Sweden.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 47Article in journal (Refereed)
    Abstract [en]

    Background

    Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs.

    Methods

    The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs.

    Results

    We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model.

    Conclusions

    Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.

  • 7.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Edström, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Tojo, James
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Kockum, Ingrid
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Olsson, Tomas
    Karolinska Institute, Sweden Centre Molecular Med, Sweden .
    Serra-Musach, Jordi
    IDIBELL, Spain .
    Bonifaci, Nuria
    IDIBELL, Spain .
    Angel Pujana, Miguel
    IDIBELL, Spain .
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment2014In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 6, no 17Article in journal (Refereed)
    Abstract [en]

    Background: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. Methods: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. Results: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. Conclusions: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

  • 8.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Lars
    Karolinska Institute, Sweden.
    Baranzini, Sergio
    University of Calif San Francisco, CA, USA.
    Bjorkander, Janne
    County Council Jonköping, Sweden.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hellberg, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Kockum, Ingrid
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Konstantinell, Aelita
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Arctic University of Norway, Norway.
    Lahesmaa, Riita
    University of Turku, Finland; Abo Akad University, Finland.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Liljenström, H. Robert I.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mattson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    County Council Jonköping, Sweden.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mendez, Melissa
    University of Peruana Cayetano Heredia, Peru.
    Olsson, Tomas
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Pujana, Miguel A.
    Catalan Institute Oncol, Spain.
    Rasool, Omid
    University of Turku, Finland; Abo Akad University, Finland.
    Serra-Musach, Jordi
    Catalan Institute Oncol, Spain.
    Stenmarker, Margaretha
    County Council Jonköping, Sweden.
    Tripathi, Subhash
    University of Turku, Finland; Abo Akad University, Finland.
    Viitala, Miro
    University of Turku, Finland; Abo Akad University, Finland.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases2015In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, no 313, article id 313ra178Article in journal (Refereed)
    Abstract [en]

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

  • 9.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barabasi, Albert-Laszlo
    Northeastern University, MA 02115 USA.
    Baranzini, Sergio
    University of Calif San Francisco, CA 94143 USA.
    Brunak, Soeren
    Technical University of Denmark, Denmark; University of Copenhagen, Denmark.
    Fan Chung, Kian
    University of London Imperial Coll Science Technology and Med, England.
    Federoff, Howard J.
    Georgetown University, DC 20057 USA.
    Gavin, Anne-Claude
    European Molecular Biol Lab, Germany.
    Meehan, Richard R.
    University of Edinburgh, Scotland.
    Picotti, Paola
    University of Zurich, Switzerland.
    Angel Pujana, Miguel
    Bellvitge Biomed Research Institute IDIBELL, Spain.
    Rajewsky, Nikolaus
    Max Delbruck Centre Molecular Med, Germany.
    Smith, Kenneth G. C.
    University of Cambridge, England; University of Cambridge, England.
    Sterk, Peter J.
    University of Amsterdam, Netherlands.
    Villoslada, Pablo
    Hospital Clin Barcelona, Spain; Hospital Clin Barcelona, Spain.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Modules, networks and systems medicine for understanding disease and aiding diagnosis2014In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 6, no 82Article, review/survey (Refereed)
    Abstract [en]

    Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.

  • 10.
    Hellberg, Sandra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Köpsén, Mattias
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Kockum, Ingrid
    Karolinska Institute, Department Clin Neurosci, Neuroimmunol Unit, S-17177 Linkoping, Sweden.
    Olsson, Tomas
    Karolinska Institute, Department Clin Neurosci, Neuroimmunol Unit, S-17177 Linkoping, Sweden.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Håkansson, Irene
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Dynamic Response Genes in CD4+T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis2016In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 16, no 11, p. 2928-2939Article in journal (Refereed)
    Abstract [en]

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

  • 11.
    Jung Lee, Eun Jung
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Lilja, Sandra
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xinxiu
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Schäfer, Samuel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Huan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Bulk and single cell transcriptomic data indicate that a dichotomy between inflammatory pathways in peripheral blood and arthritic joints complicates biomarker discovery2020In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 127, article id 154960Article in journal (Refereed)
    Abstract [en]

    Background: Unbiased studies using different genome-wide methods have identified several novel biomarkers for diagnosis and treatment response in Rheumatoid Arthritis (RA). However, clinical translation has proven difficult. Here, we hypothesized that one reason could be that inflammatory responses in peripheral blood are different from those in the arthritic joint. Methods: We performed meta-analysis of gene expression microarray data from synovium, whole blood cells (WBC), peripheral blood mononuclear cells (PBMC), and CD4+ T cells from patients with RA and healthy controls in order to identify overlapping pathways, upstream regulators and potential biomarkers. We also analyzed single cell RNA-sequencing (scRNA-seq) data from peripheral blood and whole joints from a mouse model of antigen-induced arthritis. Results: Analyses of two profiling data sets from synovium from RA patients and healthy controls all showed significant activation of pathways with known pathogenic relevance, such as the Th1 pathway, the role of NFAT in regulation of the immune response, dendritic cell maturation, iCOS-iCOSL signaling in T helper cells, Fc gamma receptor-mediated phagocytosis, interferon signaling, Cdc42 signaling, and cytotoxic T lymphocyte-mediated apoptosis. The most activated upstream regulators included TNF, an important drug target, as well as IFN-gamma and CD40LG, all of which are known to play important pathogenic roles in RA. The differentially expressed genes from synovium included several potential biomarkers, such as CCL5, CCL13, CCL18, CX3CL1, CXCL6, CXCL9, CXCL10, CXCL13, ILLS, IL32, IL1RN, SPP1, and TNFSF11. By contrast, microarray studies of WBC, PBMC and CD4+ T cells showed variable pathways and limited pathway overlap with synovium. Similarly, scRNA-seq data from a mouse model of arthritis did not support that inflammatory responses in peripheral blood reflect those in the arthritic joints. These data showed pathway overlap between mouse joint cells and synovium from patients with RA, but not with cells in peripheral blood. Conclusions: Our findings indicate a dichotomy between gene expression changes, pathways, upstream regulators and biomarkers in synovium and cell types in peripheral blood, which complicates identification of biomarkers in blood.

  • 12.
    Li, Xinxiu
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Jung Lee, Eun Jung
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Gawel, Danuta
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Schäfer, Samuel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Huan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Meta-Analysis of Expression Profiling Data Indicates Need for Combinatorial Biomarkers in Pediatric Ulcerative Colitis2020In: Journal of Immunology Research, ISSN 2314-8861, E-ISSN 2314-7156, Vol. 2020, article id 8279619Article in journal (Refereed)
    Abstract [en]

    Background. Unbiased studies using different genome-wide methods have identified a great number of candidate biomarkers for diagnosis and treatment response in pediatric ulcerative colitis (UC). However, clinical translation has been proven difficult. Here, we hypothesized that one reason could be differences between inflammatory responses in an inflamed gut and in peripheral blood cells. Methods. We performed meta-analysis of gene expression microarray data from intestinal biopsies and whole blood cells (WBC) from pediatric patients with UC and healthy controls in order to identify overlapping pathways, predicted upstream regulators, and potential biomarkers. Results. Analyses of profiling datasets from colonic biopsies showed good agreement between different studies regarding pathways and predicted upstream regulators. The most activated predicted upstream regulators included TNF, which is known to have a key pathogenic and therapeutic role in pediatric UC. Despite this, the expression levels of TNF were increased in neither colonic biopsies nor WBC. A potential explanation was increased expression of TNFR2, one of the membrane-bound receptors of TNF in the inflamed colon. Further analyses showed a similar pattern of complex relations between the expression levels of the regulators and their receptors. We also found limited overlap between pathways and predicted upstream regulators in colonic biopsies and WBC. An extended search including all differentially expressed genes that overlapped between colonic biopsies and WBC only resulted in identification of three potential biomarkers involved in the regulation of intestinal inflammation. However, two had been previously proposed in adult inflammatory bowel diseases (IBD), namely, MMP9 and PROK2. Conclusions. Our findings indicate that biomarker identification in pediatric UC is complicated by the involvement of multiple pathways, each of which includes many different types of genes in the blood or inflamed intestine. Therefore, further studies for identification of combinatorial biomarkers are warranted. Our study may provide candidate biomarkers for such studies.

  • 13.
    Ma, Tan
    et al.
    Nanjing University, Peoples R China.
    Yin, Xiaoqin
    Nanjing University, Peoples R China.
    Han, Ruitong
    Nanjing University, Peoples R China.
    Ding, Jie
    Nanjing University, Peoples R China.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Han, Xiaodong
    Nanjing University, Peoples R China.
    Li, Dongmei
    Nanjing University, Peoples R China.
    Effects of In Utero Exposure to Di-n-Butyl Phthalate on Testicular Development in Rat2017In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 14, no 10, article id 1284Article in journal (Refereed)
    Abstract [en]

    Humans are inevitably exposed to ubiquitous phthalate esters (PAEs). In utero exposure to di-n-butyl phthalate (DBP) induces abnormal development of the testis and reproductive tract in male offspring, which correspond closely with the human condition of testicular dysgenesis syndrome (TDS)-like syndrome. However, the underlying mechanisms have not been elucidated in detail. In this study, pregnant rats were orally exposed to either corn oil (controls) or DBP at three different doses by gavage during Gestational Days 12.5-21.5. Pathological examinations were performed for toxicity evaluation. Proliferation and apoptosis related proteins (ras related dexamethasone induced 1 (Rasd1), mitogen-activated protein kinase kinases1/2 (MEK1/2), Bcl-2, and Bax) were measured for mechanisms exploration. The results showed that different doses of DBP caused male developmental and reproductive toxicity in rats, including the decrease of anogenital distance (AGD), the histological damage of testis, and apoptosis of seminiferous tubule cells. Our data suggested that DBP played chronic and continuous toxic roles on male reproductive system by disrupting expression of Rasd1 and MEK1/2 as well as Bcl-2/Bax ratio. Further research is warranted.

  • 14.
    Mattson, Lina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Badam, Tejaswi
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Ledin, Torbjörn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Serra I Musach, Jordi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Björkander, Janne
    County Council Jonköping, Sweden.
    Xiang, Zou
    Hong Kong Polytech University, Peoples R China.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Potential Involvement of Type I Interferon Signaling in Immunotherapy in Seasonal Allergic Rhinitis2016In: Journal of Immunology Research, ISSN 2314-8861, E-ISSN 2314-7156, article id 5153184Article in journal (Refereed)
    Abstract [en]

    Specific immunotherapy (SIT) reverses the symptoms of seasonal allergic rhinitis (SAR) in most patients. Recent studies report type I interferons shifting the balance between type I T helper cell (Th1) and type II T helper cells (Th2) towards Th2 dominance by inhibiting the differentiation of naive Tcells into Th1 cells. As SIT is thought to cause a shift towardsTh1 dominance, we hypothesized that SIT would alter interferon type I signaling. To test this, allergen and diluent challenged CD4(+) T cells from healthy controls and patients from different time points were analyzed. The initial experiments focused on signature genes of the pathway and found complex changes following immunotherapy, which were consistent with our hypothesis. As interferon signaling involves multiple genes, expression profiling studies were performed, showing altered expression of the pathway. These findings require validation in a larger group of patients in further studies.

  • 15.
    Nestor, Colm
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Barrenäs, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bruhn, Sören
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Jornsten, Rebecka
    University of Gothenburg, Sweden .
    Langston, Michael A.
    University of Tennessee, TN USA .
    Rogers, Gary
    University of Tennessee, TN USA .
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    DNA Methylation Changes Separate Allergic Patients from Healthy Controls and May Reflect Altered CD4(+) T-Cell Population Structure2014In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 1, p. e1004059-Article in journal (Refereed)
    Abstract [en]

    Altered DNA methylation patterns in CD4(+) T-cells indicate the importance of epigenetic mechanisms in inflammatory diseases. However, the identification of these alterations is complicated by the heterogeneity of most inflammatory diseases. Seasonal allergic rhinitis (SAR) is an optimal disease model for the study of DNA methylation because of its welldefined phenotype and etiology. We generated genome-wide DNA methylation (N-patients = 8, N-controls = 8) and gene expression (N-patients = 9, N-controls = 10) profiles of CD4(+) T-cells from SAR patients and healthy controls using Illuminas HumanMethylation450 and HT-12 microarrays, respectively. DNA methylation profiles clearly and robustly distinguished SAR patients from controls, during and outside the pollen season. In agreement with previously published studies, gene expression profiles of the same samples failed to separate patients and controls. Separation by methylation (N-patients = 12, N-controls = 12), but not by gene expression (N-patients = 21, N-controls = 21) was also observed in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen. We observed changes in the proportions of memory T-cell populations between patients (N-patients = 35) and controls (N-controls = 12), which could explain the observed difference in DNA methylation. Our data highlight the potential of epigenomics in the stratification of immune disease and represents the first successful molecular classification of SAR using CD4(+) T cells.

  • 16.
    Nestor, Colm E
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Dadfa, Elham
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Björkander, Jan Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Sublingual immunotherapy alters expression of IL-4 and its soluble and membrane-bound receptors2014In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no 11, p. 1564-1566Article in journal (Refereed)
    Abstract [en]

    Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which results from an inappropriate T-helper cell, type 2 (Th2) response to pollen. Specific immunotherapy (SIT) involves repeated treatment with small doses of pollen and can result in complete and lasting reversal of SAR. Here, we assayed the key Th2 cytokine, IL-4, and its soluble and membrane-bound receptor in SAR patients before and after SIT. Using allergen-challenge assays, we found that SIT treatment decreased IL-4 cytokine levels, as previously reported. We also observed a significant decrease in the IL-4 membrane-bound receptor (mIL4R) at both the level of mRNA and protein. SIT treatment resulted in a significant increase in the inhibitory soluble IL-4 receptor (sIL4R). Reciprocal changes in mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a novel explanation for the positive effects of immunotherapy with potential basic and clinical research implications.

  • 17.
    Nestor, Colm
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hägg Nilsson, Cathrine
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Mattson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Wang, Hui
    MD Anderson Cancer Centre, TX 77030 USA.
    Rundquist, Olof
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Meehan, Richard R.
    University of Edinburgh, Scotland.
    Klocke, Bernward
    Genomatix Software GmbH, Germany.
    Seifert, Martin
    Genomatix Software GmbH, Germany.
    Hauck, Stefanie M.
    German Research Centre Environm Health GmbH, Germany.
    Laumen, Helmut
    Technical University of Munich, Germany; Technical University of Munich, Germany; Helmholtz Zentrum Munchen, Germany; Technical University of Munich, Germany; Technical University of Munich, Germany.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    5-Hydroxymethylcytosine Remodeling Precedes Lineage Specification during Differentiation of Human CD4(+) T Cells2016In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 16, no 2, p. 559-570Article in journal (Refereed)
    Abstract [en]

    5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by the TET family of enzymes as part of a recently discovered active DNA de-methylation pathway. 5hmC plays important roles in regulation of gene expression and differentiation and has been implicated in T cell malignancies and autoimmunity. Here, we report early and widespread 5mC/5hmC remodeling during human CD4(+) T cell differentiation ex vivo at genes and cell-specific enhancers with known T cell function. We observe similar DNA de-methylation in CD4(+) memory T cells in vivo, indicating that early remodeling events persist long term in differentiated cells. Underscoring their important function, 5hmC loci were highly enriched for genetic variants associated with T cell diseases and T-cell-specific chromosomal interactions. Extensive functional validation of 22 risk variants revealed potentially pathogenic mechanisms in diabetes and multiple sclerosis. Our results support 5hmC-mediated DNA de-methylation as a key component of CD4(+) T cell biology in humans, with important implications for gene regulation and lineage commitment.

  • 18.
    Sun, Kwang-Hsiao
    et al.
    Nanjing University, Peoples R China.
    Liu, Zhao
    Nanjing University, Peoples R China.
    Liu, Chang-Jian
    Nanjing University, Peoples R China.
    Yu, Tong
    Nanjing University, Peoples R China.
    Zhou, Min
    Nanjing University, Peoples R China.
    Liu, Cheng
    Nanjing University, Peoples R China.
    Ran, Feng
    Nanjing University, Peoples R China.
    Pan, Li-Jia
    Nanjing University, Peoples R China.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    In vivo study of alginate hydrogel conglutinating cells to polycaprolactone vascular scaffolds fabricated by electrospinning2017In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 105, no 8, p. 2443-2454Article in journal (Refereed)
    Abstract [en]

    Objective The aim of this study was to explore an innovative cell-seeding technology applied on artificial vascular scaffolds. Methods Scaffolds were fabricated by electrospinning polycaprolactone (PCL) and seeded with rat endothelial progenitor cells differentiated from adipose-derived stem cells. Then, we modified the PCL scaffolds through the use of alginate hydrogel conglutinating cells (AHCC), a blank alginate hydrogel coating (BAHC), and natural sedimentation seeding cells (NSSC). The blank PCL (BP) scaffolds without any modifications were considered the blank control group. After modification, the scaffolds were implanted in a rat model. The implanted scaffolds were harvested and observed using histological and immunohistochemical methods and scanning electron microscopy (SEM) at 1, 2, and 4weeks after implantation, respectively. Results The best regeneration and configuration of the endothelium tissue and the most similar morphology to that of natural endangium was observed qualitatively in the AHCC scaffolds. The BP scaffolds had qualitatively the worst regeneration and configuration and the most dissimilar morphology at the same time point. In the AHCC group, cells could adhere directly on the inner surface of the vascular scaffolds, eliminating the time delay via the NSSC method prior to cell adhesion. Conclusion AHCC are an effective method for seeding cells on vascular scaffolds and can eliminate the time delay for cell adhesion. (C) 2016 Wiley Periodicals, Inc.

  • 19.
    Wang, Hui
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    GAB2 regulates type 2 T helper cell differentiation in humans2017In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 96, p. 234-237Article in journal (Refereed)
    Abstract [en]

    Th2 cell differentiation involves complex changes in expression of multiple genes, many of which have poorly characterized roles. In a gene expression microarray analysis of human primary CD4(+) effector T subsets, we identified that an adaptor protein, GAB2, was preferentially expressed in human Th2 cells. The role of GAB2 in human Th2 cells is unknown. Through analysis of primary and in vitro differentiated human T effector subsets, we confirmed that human Th2 cells preferentially expressed GAB2. Further analysis of public gene expression microarray data of STAT6-knockdowned Th2 cells indicated that GAB2 expression was regulated by IL-4 and STAT6. Both siRNA knockdown and ectopic expression of GAB2 in activated T cells showed that GAB2 positively regulated IL-4 and IL-13 expression in human Th2 cells. We hence identified the adaptor protein, GAB2, as an important novel regulator of the human Th2 immune response.

  • 20.
    Yin, Xiaoqin
    et al.
    Nanjing Univ, Peoples R China.
    Ma, Tan
    Nanjing Univ, Peoples R China.
    Han, Ruitong
    Nanjing Univ, Peoples R China.
    Ding, Jie
    Nanjing Univ, Peoples R China.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Han, Xiaodong
    Nanjing Univ, Peoples R China.
    Li, Dongmei
    Nanjing Univ, Peoples R China.
    MiR-301b-3p/3584-5p enhances low-dose mono-n-butyl phthalate (MBP) induced proliferation by targeting Rasd1 in Sertoli cells2018In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 47, p. 79-88Article in journal (Refereed)
    Abstract [en]

    To investigate the possible molecular mechanism of low concentration plasticizer mono-n-butyl phthalate (MBP)-induced juvenile Sertoli cells (SCs) proliferation, we evaluated global alterations of miRNA and mRNA expression in rat SCs treated with 0.1 mM MBP. Microarray analysis revealed that miR-3584-5p and miR-301b-3p were up-regulated and their common target gene Dexamethasone-induced Ras-related protein 1 (Rasd1) was down-regulated. Further work suggested that SCs proliferation induced by low concentration MBP in vitro might be mediated by Rasd1 regulating ERK1/2 signaling pathway. The present study is first to investigate the effect of low-dose MBP on SCs proliferation and may enhance our understanding on the modes of action of low concentration MBP on male reproductive system. We hope the results will contribute to explain the causes of precocious puberty and testicular tumors induced by exogenous chemicals.

  • 21.
    Zhang, Huan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Cardell, Lars Olaf
    Division of ENT diseases Huddinge, CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Björkander, Janne
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Comprehensive Profiling of Peripheral Immune Cells and Subsets in Patients with Intermittent Allergic Rhinitis Compared to Healthy Controls and After Treatment with Glucocorticoids2013In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 36, no 4, p. 821-829Article in journal (Refereed)
    Abstract [en]

    Intermittent allergic rhinitis (IAR) is a common allergic disease, which is associated with local infiltration of T cells, eosinophils, and basophils. However, changes of circulating inflammatory cells may reflect local and systemic allergic inflammation and potentially, also the response to treatment with glucocorticoids (GCs). In this study, we comprehensively profiled peripheral blood immune cells and subsets from 12 patients with IAR during the birch pollen season before and after GC treatment and nine healthy controls by flow cytometry. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified that peripheral immune cells and subsets markedly separated symptomatic patients and controls. Eosinophils, basophils, and Th2 cells contributed most to the separation. However, there was no good separation between patients before and after GC treatment. Local allergic inflammation in the nasal mucosa is associated with increased circulating Th2 cells, eosinophils, and basophils. Local GC treatment has limited effects on circulating immune cells.

  • 22.
    Zhang, Huan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Chung, Kian Fan
    Experimental Studies, National Heart and Lung Institute, Imperial College London, London, UK / NIHR Respiratory Biomedical Research Unit at the Royal Brompton NHS Foundation Trust and Imperial College London, London, UK; Royal Brompton NHS Fdn Trust, NIHR Resp Biomed Res Unit, London, England.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Targeted omics and systems medicine: personalising care2014In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 2, no 10, p. 785-787Article in journal (Other academic)
  • 23.
    Zhang, Huan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Klareskog, Lars
    Karolinska Inst, Sweden.
    Matussek, Andreas
    Karolinska Univ Hosp Lab, Sweden.
    Pfister, Stefan M.
    Hopp Childrens Canc Ctr Heidelberg KiTZ, Germany; German Canc Res Ctr, Germany; German Canc Consortium DKTK, Germany; Heidelberg Univ Hosp, Germany.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Editorial Material: Translating genomic medicine to the clinic: challenges and opportunities in GENOME MEDICINE, vol 11, issue , pp2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 9Article in journal (Other academic)
    Abstract [en]

    Editorial summaryGenomic medicine has considerable potential to provide novel diagnostic and therapeutic solutions for patients who have molecularly complex diseases and who are not responding to existing therapies. To bridge the gap between genomic medicine and clinical practice, integration of various data types, resources, and joint international initiatives will be required.

  • 24.
    Zhang, Huan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Zhao, Shuli
    Nanjing Medical University, Nanjing, China.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Bohle, Barbara
    Medical University of Vienna, Austria.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Profiling of human CD4+ T-cell subsets identifies the TH2-specific noncoding RNA GATA3-AS12013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 132, no 4, p. 1005-1008Article in journal (Other academic)
  • 25.
    Zhang, Ling
    et al.
    Nanjing University, Peoples R China.
    Zhang, Hui
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Nanjing University, Peoples R China.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Nanjing University, Peoples R China.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Han, Xiaodong
    Nanjing University, Peoples R China.
    Li, Dongmei
    Nanjing University, Peoples R China.
    Roles of piRNAs in microcystin-leucine-arginine (MC-LR) induced reproductive toxicity in testis on male offspring2017In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 105, p. 177-185Article in journal (Refereed)
    Abstract [en]

    In the present study, we evaluated the toxic effects on the testis of the male offspring of MC-LR exposure during fetal and lactational periods. Pregnant females were distributed into two experimental groups: control group and MC-LR group which were exposed to 0 and 10 mu g/L of MC-LR, respectively, through drinking water separately during fetal and lactational periods. At the age of 30 days after birth, the male offspring were euthanized. The body weight, testis index, and histomorphology change were observed and the global changes of piwi-interacting RNA (piRNA) expression were evaluated. The results revealed that MC-LR was found in the testis of male offspring, body weight and testis index decreased significantly, and testicular tissue structure was damaged in the MC-LR group. In addition, the exposure to MCLR resulted in an altered piRNA expression profile and an increase of the cell apoptosis and a decrease of the cell proliferation in the testis of the male offspring. It was reasonable to speculate that the toxic effects on reproductive system of the male offspring in MC-LR group might be mediated by piRNAs through the regulation of the target genes. As far as we are aware, this is the first report showing that MC-LR could play a role in disorder of proliferative and cell apoptosis in the testis of the male offspring by the maternal transmission effect of toxicity. (C) 2017 Elsevier Ltd. All rights reserved.

1 - 25 of 25
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf