Umeå University's logo

umu.sePublications
Change search
Refine search result
12 1 - 50 of 78
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • 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.
    AbdelMageed, Manar
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
    Ali, Haytham
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
    Ohlsson, Lina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Lindmark, Gudrun
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    The Chemokine CXCL16 Is a New Biomarker for Lymph Node Analysis of Colon Cancer Outcome2019In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 20, no 22, article id 5793Article in journal (Refereed)
    Abstract [en]

    hemokines are important in the development and progression of tumors. We investigated the expression of CXCL14 and CXCL16 in colon cancer. Expression of mRNA was assessed in primary tumors and lymph nodes and CXCL16 mRNA levels were correlated to patient’s survival. Protein expression was investigated by two-color immunofluorescence and immunomorphometry. CXCL14 and CXCL16 mRNA levels and protein expression were significantly higher in colon cancer primary tumors compared to apparently normal colon tissue. Positive cells were tumor cells, as revealed by anti-CEA and anti-EpCAM staining. CXCL16, but not CXCL14, mRNA levels were significantly higher in hematoxylin and eosin positive (H&E(+)) compared to H&E(−) colon cancer lymph nodes or control nodes (P < 0.0001). CXCL16 mRNA was expressed in 5/5 colon cancer cell lines while CXCL14 was expressed significantly in only one. Kaplan-Meier analysis revealed that colon cancer patients with lymph nodes expressing high or very high levels (7.2 and 11.4 copies/18S rRNA unit, respectively) of CXCL16 mRNA had a decreased mean survival time of 30 and 46 months at the 12-year follow-up (P = 0.04, P = 0.005, respectively). In conclusion, high expression of CXCL16 mRNA in regional lymph nodes of colon cancer patients is a sign of a poor prognosis.

    Download full text (pdf)
    fulltext
  • 2.
    AbdelMageed, Manar
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
    Ismail, Hager
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
    Ohlsson, Lina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Lindmark, Gudrun
    Institution of Clinical Sciences, Lund University, Helsingborg, Sweden.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Clinical significance of stem cell biomarkers epcam, lgr5 and lgr4 mrna levels in lymph nodes of colon cancer patients2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 1, article id 403Article in journal (Refereed)
    Abstract [en]

    The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan‐Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA cop-ies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM and 42 months for both LGR5 and LGR4 at a 12‐year follow‐up (p = 0.022, p = 0.005 and p = 0.011, respec-tively). Additional patients at risk for recurrence were detected when LGR5 was combined with the biomarkers CXCL17 or CEA plus CXCL16. In conclusion, the study underscores LGR5 as a particularly useful prognostic biomarker and illustrates the strength of combining biomarkers detecting different subpopulations of cancer cells and/or cells in the tumor microenvironment for predicting recurrence.

    Download full text (pdf)
    fulltext
  • 3.
    Akhunzianov, Almaz A.
    et al.
    Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation.
    Nesterova, Alfiya I.
    Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation; Republican Clinical Oncology Dispensary Named after Prof. M.Z. Sigal, Kazan, Russian Federation.
    Wanrooij, Sjoerd
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Filina, Yulia V.
    Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation.
    Rizvanov, Albert A.
    Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation.
    Miftakhova, Regina R.
    Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation.
    Unravelling the Therapeutic Potential of Antibiotics in Hypoxia in a Breast Cancer MCF-7 Cell Line Model2023In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, no 14, article id 11540Article in journal (Refereed)
    Abstract [en]

    Antibiotics inhibit breast cancer stem cells (CSCs) by suppressing mitochondrial biogenesis. However, the effectiveness of antibiotics in clinical settings is inconsistent. This inconsistency raises the question of whether the tumor microenvironment, particularly hypoxia, plays a role in the response to antibiotics. Therefore, the goal of this study was to evaluate the effectiveness of five commonly used antibiotics for inhibiting CSCs under hypoxia using an MCF-7 cell line model. We assessed the number of CSCs through the mammosphere formation assay and aldehyde dehydrogenase (ALDH)-bright cell count. Additionally, we examined the impact of antibiotics on the mitochondrial stress response and membrane potential. Furthermore, we analyzed the levels of proteins associated with therapeutic resistance. There was no significant difference in the number of CSCs between cells cultured under normoxic and hypoxic conditions. However, hypoxia did affect the rate of CSC inhibition by antibiotics. Specifically, azithromycin was unable to inhibit sphere formation in hypoxia. Erythromycin and doxycycline did not reduce the ratio of ALDH-bright cells, despite decreasing the number of mammospheres. Furthermore, treatment with chloramphenicol, doxycycline, and tetracycline led to the overexpression of the breast cancer resistance protein. Our findings suggest that hypoxia may weaken the inhibitory effects of antibiotics on the breast cancer model.

    Download full text (pdf)
    fulltext
  • 4.
    Anerillas, Luis Oliveros
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Three-dimensional osteogenic differentiation of bone marrow mesenchymal stem cells promotes matrix metallopeptidase 13 (Mmp13) expression in type i collagen hydrogels2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 24, article id 13594Article in journal (Refereed)
    Abstract [en]

    Autologous bone transplantation is the principal method for reconstruction of large bone defects. This technique has limitations, such as donor site availability, amount of bone needed and morbidity. An alternative to this technique is tissue engineering with bone marrow-derived mesenchymal stem cells (BMSCs). In this study, our aim was to elucidate the benefits of culturing BMSCs in 3D compared with the traditional 2D culture. In an initial screening, we combined BMSCs with four different biogels: unmodified type I collagen (Col I), type I collagen methacrylate (ColMa), an alginate and cellulose-based bioink (CELLINK) and a gelatin-based bioink containing xanthan gum (GelXA-bone). Col I was the best for structural integrity and maintenance of cell morphology. Osteogenic, adipogenic, and chondrogenic differentiations of the BMSCs in 2D versus 3D type I collagen gels were investigated. While the traditional pellet culture for chondrogenesis was superior to our tested 3D culture, Col I hydrogels (i.e., 3D) favored adipogenic and osteogenic differentiation. Further focus of this study on osteogenesis were conducted by comparing 2D and 3D differentiated BMSCs with Osteoimage® (stains hydroxyapatite), von Kossa (stains anionic portion of phosphates, carbonates, and other salts) and Alizarin Red (stains Ca2+ deposits). Multivariate gene analysis with various covariates showed low variability among donors, successful osteogenic differentiation, and the identification of one gene (matrix metallopeptidase 13, MMP13) significantly differentially expressed in 2D vs. 3D cultures. MMP13 protein expression was confirmed with immunohistochemistry. In conclusion, this study shows evidence for the suitability of type I collagen gels for 3D osteogenic differentiation of BMSCs, which might improve the production of tissue-engineered constructs for treatment of bone defects.

    Download full text (pdf)
    fulltext
  • 5.
    Arabuli, Lili
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Department of Natural Sciences, School of Science and Technology, University of Georgia, Tbilisi, Georgia.
    Iashchishyn, Igor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Romanova, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Musteikyte, Greta
    Smirnovas, Vytautas
    Chaudhary, Himanshu
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Svedružić, Željko M.
    Morozova-Roche, Ludmilla A.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Co-aggregation of S100A9 with DOPA and cyclen-based compounds manifested in amyloid fibril thickening without altering rates of self-assembly2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 16, article id 8556Article in journal (Refereed)
    Abstract [en]

    The amyloid cascade is central for the neurodegeneration disease pathology, including Alzheimer’s and Parkinson’s, and remains the focus of much current research. S100A9 protein drives the amyloid-neuroinflammatory cascade in these diseases. DOPA and cyclen-based compounds were used as amyloid modifiers and inhibitors previously, and DOPA is also used as a precursor of dopamine in Parkinson’s treatment. Here, by using fluorescence titration experiments we showed that five selected ligands: DOPA-D-H-DOPA, DOPA-H-H-DOPA, DOPA-D-H, DOPA-cyclen, and H-E-cyclen, bind to S100A9 with apparent Kd in the sub-micromolar range. Ligand docking and molecular dynamic simulation showed that all compounds bind to S100A9 in more than one binding site and with different ligand mobility and H-bonds involved in each site, which all together is consistent with the apparent binding determined in fluorescence experiments. By using amyloid kinetic analysis, monitored by thioflavin-T fluorescence, and AFM imaging, we found that S100A9 co-aggregation with these compounds does not hinder amyloid formation but leads to morphological changes in the amyloid fibrils, manifested in fibril thickening. Thicker fibrils were not observed upon fibrillation of S100A9 alone and may influence the amyloid tissue propagation and modulate S100A9 amyloid assembly as part of the amyloid-neuroinflammatory cascade in neurodegenerative diseases.

    Download full text (pdf)
    fulltext
  • 6.
    Attaran, Nima
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Gu, Xiaolian
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip J
    Fåhraeus, Robin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wilms, Torben
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Wang, Lixiao
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sgaramella, Nicola
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zborayova, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival.2020In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 21, no 17, article id E6220Article in journal (Refereed)
    Abstract [en]

    Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.

    Download full text (pdf)
    fulltext
  • 7. Boldinova, Elizaveta O.
    et al.
    Wanrooij, Paulina H.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Shilkin, Evgeniy S.
    Wanrooij, Sjoerd
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Makarova, Alena V.
    DNA Damage Tolerance by Eukaryotic DNA Polymerase and Primase PrimPol2017In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 18, no 7, article id 1584Article, review/survey (Refereed)
    Abstract [en]

    PrimPol is a human deoxyribonucleic acid (DNA) polymerase that also possesses primase activity and is involved in DNA damage tolerance, the prevention of genome instability and mitochondrial DNA maintenance. In this review, we focus on recent advances in biochemical and crystallographic studies of PrimPol, as well as in identification of new protein-protein interaction partners. Furthermore, we discuss the possible functions of PrimPol in both the nucleus and the mitochondria.

    Download full text (pdf)
    fulltext
  • 8.
    Boles, Usama
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Cardiology Department, Letterkenny University Hospital, Letterkenny, Co. Donegal, Ireland.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sharif, Zain
    David, Santhosh
    McGrory, Siobhan
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Molecular & Clinical Sciences Research Institute, St. George University, London, UK.
    Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis2018In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 19, no 1, article id 260Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coronary artery ectasia (CAE) is a rare disorder commonly associated with additional features of atherosclerosis. In the present study, we aimed to examine the systemic immune-inflammatory response that might associate CAE.

    METHODS: Plasma samples were obtained from 16 patients with coronary artery ectasia (mean age 64.9 ± 7.3 years, 6 female), 69 patients with coronary artery disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 ± 8.7 years, 41 female), and 140 controls (mean age 58.6 ± 4.1 years, 40 female) with normal coronary arteries. Samples were analyzed at Umeå University Biochemistry Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit. Statistically significant differences (p < 0.05) between patient groups and controls were determined using Mann-Whitney U-tests.

    RESULTS: The CAE patients had significantly higher plasma levels of INF-γ, TNF-α, IL-1β, and IL-8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma levels of IL-10, IL-12p, and IL-13 were not different between the three groups. None of these markers could differentiate between patients with pure (n = 6) and mixed with minimal atherosclerosis (n = 10) CAE.

    CONCLUSIONS: These results indicate an enhanced systemic pro-inflammatory response in CAE. The profile of this response indicates activation of macrophages through a pathway and trigger different from those of atherosclerosis immune inflammatory response.

    Download full text (pdf)
    fulltext
  • 9.
    Bonczek, Ondrej
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Research Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute (MMCI), Zluty Kopec 7, Brno, Czech Republic.
    Wang, Lixiao
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Gnanasundram, Sivakumar Vadivel
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Chen, Sa
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Haronikova, Lucia
    Research Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute (MMCI), Zluty Kopec 7, Brno, Czech Republic.
    Zavadil-Kokas, Filip
    Research Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute (MMCI), Zluty Kopec 7, Brno, Czech Republic.
    Vojtesek, Borivoj
    Research Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute (MMCI), Zluty Kopec 7, Brno, Czech Republic.
    DNA and RNA Binding Proteins: From Motifs to Roles in Cancer2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 16, article id 9329Article, review/survey (Refereed)
    Abstract [en]

    DNA and RNA binding proteins (DRBPs) are a broad class of molecules that regulate numerous cellular processes across all living organisms, creating intricate dynamic multilevel networks to control nucleotide metabolism and gene expression. These interactions are highly regulated, and dysregulation contributes to the development of a variety of diseases, including cancer. An increasing number of proteins with DNA and/or RNA binding activities have been identified in recent years, and it is important to understand how their activities are related to the molecular mechanisms of cancer. In addition, many of these proteins have overlapping functions, and it is therefore essential to analyze not only the loss of function of individual factors, but also to group abnormalities into specific types of activities in regard to particular cancer types. In this review, we summarize the classes of DNA-binding, RNA-binding, and DRBPs, drawing particular attention to the similarities and differences between these protein classes. We also perform a cross-search analysis of relevant protein databases, together with our own pipeline, to identify DRBPs involved in cancer. We discuss the most common DRBPs and how they are related to specific cancers, reviewing their biochemical, molecular biological, and cellular properties to highlight their functions and potential as targets for treatment.

    Download full text (pdf)
    fulltext
  • 10.
    Crepin, Aurélie
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický Mlýn, Třeboň, Czech Republic.
    Belgio, Erica
    Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický Mlýn, Třeboň, Czech Republic.
    Šedivá, Barbora
    Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický Mlýn, Třeboň, Czech Republic.
    Trsková, Eliška Kuthanová
    Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický Mlýn, Třeboň, Czech Republic.
    Cunill-Semanat, Edel
    Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický Mlýn, Třeboň, Czech Republic.
    Kaňa, Radek
    Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický Mlýn, Třeboň, Czech Republic.
    Size and Fluorescence Properties of Algal Photosynthetic Antenna Proteins Estimated by Microscopy2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 2, article id 778Article in journal (Refereed)
    Abstract [en]

    Antenna proteins play a major role in the regulation of light-harvesting in photosynthe-sis. However, less is known about a possible link between their sizes (oligomerization state) and fluorescence intensity (number of photons emitted). Here, we used a microscopy-based method, Fluorescence Correlation Spectroscopy (FCS), to analyze different antenna proteins at the particle level. The direct comparison indicated that Chromera Light Harvesting (CLH) antenna particles (isolated from Chromera velia) behaved as the monomeric Light Harvesting Complex II (LHCII) (from higher plants), in terms of their radius (based on the diffusion time) and fluorescence yields. FCS data thus indicated a monomeric oligomerization state of algal CLH antenna (at our experimental conditions) that was later confirmed also by biochemical experiments. Additionally, our data provide a proof of concept that the FCS method is well suited to measure proteins sizes (oligomerization state) and fluorescence intensities (photon counts) of antenna proteins per single particle (monomers and oligomers). We proved that antenna monomers (CLH and LHCIIm) are more “quenched” than the corresponding trimers. The FCS measurement thus represents a useful experimental approach that allows studying the role of antenna oligomerization in the mechanism of photoprotection.

    Download full text (pdf)
    fulltext
  • 11.
    Decker, Daniel
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Aubert, Juliette
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Wilczynska, Malgorzata
    Diamyd Medical, Umeå, Sweden.
    Kleczkowski, Leszek A.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Exploring redox modulation of plant UDP-glucose pyrophosphorylase2023In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, no 10, article id 8914Article in journal (Refereed)
    Abstract [en]

    UDP-glucose (UDPG) pyrophosphorylase (UGPase) catalyzes a reversible reaction, producing UDPG, which serves as an essential precursor for hundreds of glycosyltransferases in all organisms. In this study, activities of purified UGPases from sugarcane and barley were found to be reversibly redox modulated in vitro through oxidation by hydrogen peroxide or oxidized glutathione (GSSG) and through reduction by dithiothreitol or glutathione. Generally, while oxidative treatment decreased UGPase activity, a subsequent reduction restored the activity. The oxidized enzyme had increased Km values with substrates, especially pyrophosphate. The increased Km values were also observed, regardless of redox status, for UGPase cysteine mutants (Cys102Ser and Cys99Ser for sugarcane and barley UGPases, respectively). However, activities and substrate affinities (Kms) of sugarcane Cys102Ser mutant, but not barley Cys99Ser, were still prone to redox modulation. The data suggest that plant UGPase is subject to redox control primarily via changes in the redox status of a single cysteine. Other cysteines may also, to some extent, contribute to UGPase redox status, as seen for sugarcane enzymes. The results are discussed with respect to earlier reported details of redox modulation of eukaryotic UGPases and regarding the structure/function properties of these proteins.

    Download full text (pdf)
    fulltext
  • 12. Falak, Noreen
    et al.
    Imran, Qari Muhammad
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Laboratory of Plant Functional Genomics, School of Applied Biosciences, Kyungpook National University, Daegu, Korea.
    Hussain, Adil
    Yun, Byung-Wook
    Transcription Factors as the "Blitzkrieg" of Plant Defense: A Pragmatic View of Nitric Oxide's Role in Gene Regulation2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 2, article id 522Article, review/survey (Refereed)
    Abstract [en]

    Plants are in continuous conflict with the environmental constraints and their sessile nature demands a fine-tuned, well-designed defense mechanism that can cope with a multitude of biotic and abiotic assaults. Therefore, plants have developed innate immunity, R-gene-mediated resistance, and systemic acquired resistance to ensure their survival. Transcription factors (TFs) are among the most important genetic components for the regulation of gene expression and several other biological processes. They bind to specific sequences in the DNA called transcription factor binding sites (TFBSs) that are present in the regulatory regions of genes. Depending on the environmental conditions, TFs can either enhance or suppress transcriptional processes. In the last couple of decades, nitric oxide (NO) emerged as a crucial molecule for signaling and regulating biological processes. Here, we have overviewed the plant defense system, the role of TFs in mediating the defense response, and that how NO can manipulate transcriptional changes including direct post-translational modifications of TFs. We also propose that NO might regulate gene expression by regulating the recruitment of RNA polymerase during transcription.

    Download full text (pdf)
    fulltext
  • 13.
    Fernández-Vázquez, Jorge
    et al.
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.
    Cabrer-Panes, Juan David
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.
    Åberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Juárez, Antonio
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain; Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, Spain.
    Madrid, Cristina
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.
    Gaviria-Cantin, Tania
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.
    Fernández-Coll, Llorenç
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.
    Vargas-Sinisterra, Andrés Felipe
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.
    Jiménez, Carlos Jonay
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.
    Balsalobre, Carlos
    Department of Genetics, Microbiology and Statistics, School of Biology, University of Barcelona, Barcelona, Spain.
    ppGpp, the general stress response alarmone, is required for the expression of the α-Hemolysin toxin in the uropathogenic Escherichia coli isolate, J962022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 20, article id 12256Article in journal (Refereed)
    Abstract [en]

    ppGpp is an intracellular sensor that, in response to different types of stress, coordinates the rearrangement of the gene expression pattern of bacteria to promote adaptation and survival to new environmental conditions. First described to modulate metabolic adaptive responses, ppGpp modulates the expression of genes belonging to very diverse functional categories. In Escherichia coli, ppGpp regulates the expression of cellular factors that are important during urinary tract infections. Here, we characterize the role of this alarmone in the regulation of the hlyCABDII operon of the UPEC isolate J96, encoding the toxin α-hemolysin that induces cytotoxicity during infection of bladder epithelial cells. ppGpp is required for the expression of the α-hemolysin encoded in hlyCABDII by stimulating its transcriptional expression. Prototrophy suppressor mutations in a ppGpp-deficient strain restore the α-hemolysin expression from this operon to wild-type levels, confirming the requirement of ppGpp for its expression. ppGpp stimulates hlyCABDII expression independently of RpoS, RfaH, Zur, and H-NS. The expression of hlyCABDII is promoted at 37 °C and at low osmolarity. ppGpp is required for the thermoregulation but not for the osmoregulation of the hlyCABDII operon. Studies in both commensal and UPEC isolates demonstrate that no UPEC specific factor is strictly required for the ppGpp-mediated regulation described. Our data further support the role of ppGpp participating in the coordinated regulation of the expression of bacterial factors required during infection.

    Download full text (pdf)
    fulltext
  • 14. Gnanasundram, Sivakumar Vadivel
    et al.
    Fåhraeus, Robin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Translation Stress Regulates Ribosome Synthesis and Cell Proliferation2018In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 19, no 12, article id 3757Article, review/survey (Refereed)
    Abstract [en]

    Ribosome and protein synthesis are major metabolic events that control cellular growth and proliferation. Impairment in ribosome biogenesis pathways and mRNA translation is associated with pathologies such as cancer and developmental disorders. Processes that control global protein synthesis are tightly regulated at different levels by numerous factors and linked with multiple cellular signaling pathways. Several of these merge on the growth promoting factor c-Myc, which induces ribosome biogenesis by stimulating Pol I, Pol II, and Pol III transcription. However, how cells sense and respond to mRNA translation stress is not well understood. It was more recently shown that mRNA translation stress activates c-Myc, through a specific induction of E2F1 synthesis via a PI3K delta-dependent pathway. This review focuses on how this novel feedback pathway stimulates cellular growth and proliferation pathways to synchronize protein synthesis with ribosome biogenesis. It also describes for the first time the oncogenic activity of the mRNA, and not the encoded protein.

    Download full text (pdf)
    fulltext
  • 15.
    Haase, Tina
    et al.
    University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany.
    Müller, Christian
    University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany.
    Stoffers, Bastian
    University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany.
    Kirn, Philipp
    German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Waldenberger, Melanie
    Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Neuherberg, Germany.
    Kaiser, Frank J.
    Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
    Karakas, Mahir
    German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Kim, Sangwon V.
    Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, PA, Philadelphia, United States.
    Voss, Svenja
    University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany.
    Wild, Philipp S.
    Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.
    Lackner, Karl J.
    German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lindner, Diana
    University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany.
    Zeller, Tanja
    German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; University Center of Cardiovascular Science, University Heart Vascular Center Hamburg, Hamburg, Germany.
    G protein-coupled receptor 15 expression is associated with myocardial infarction2023In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, no 1, article id 180Article in journal (Refereed)
    Abstract [en]

    Beyond the influence of lifestyle-related risk factors for myocardial infarction (MI), the mechanisms of genetic predispositions for MI remain unclear. We sought to identify and characterize differentially expressed genes in early-onset MI in a translational approach. In an observational case–control study, transcriptomes from 112 early-onset MI individuals showed upregulated G protein-coupled receptor 15 (GPR15) expression in peripheral blood mononuclear cells compared to controls (fold change = 1.4, p = 1.87 × 10−7). GPR15 expression correlated with intima-media thickness (β = 0.8498, p = 0.111), C-reactive protein (β = 0.2238, p = 0.0052), ejection fraction (β = −0.9991, p = 0.0281) and smoking (β = 0.7259, p = 2.79 × 10−10). The relation between smoking and MI was diminished after the inclusion of GPR15 expression as mediator in mediation analysis (from 1.27 (p = 1.9 × 10−5) to 0.46 (p = 0.21)). The DNA methylation of two GPR15 sites was 1%/5% lower in early-onset MI individuals versus controls (p = 2.37 × 10−6/p = 0.0123), with site CpG3.98251219 significantly predicting risk for incident MI (hazard ratio = 0.992, p = 0.0177). The nucleotide polymorphism rs2230344 (C/T) within GPR15 was associated with early-onset MI (odds ratio = 3.61, p = 0.044). Experimental validation showed 6.3-fold increased Gpr15 expression in an ischemic mouse model (p < 0.05) and 4-fold increased Gpr15 expression in cardiomyocytes under ischemic stress (p < 0.001). After the induction of MI, Gpr15gfp/gfp mice showed lower survival (p = 0.042) and deregulated gene expression for response to hypoxia and signaling pathways. Using a translational approach, our data provide evidence that GPR15 is linked to cardiovascular diseases, mediating the adverse effects of smoking.

    Download full text (pdf)
    fulltext
  • 16.
    Henein, Michael Y.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Institute of Environment Health and Societies, Brunel University, Middlesex, United Kingdom; Molecular and Clinical Sciences Research Institute, St. George’s University, London, United Kingdom.
    Vancheri, Sergio
    Interventional Neuroradiology Department, Besançon University Hospital, Besançon, France.
    Longo, Giovanni
    Cardiovascular and Interventional Department, S.Elia Hospital, Caltanissetta, Italy.
    Vancheri, Federico
    Department of Internal Medicine, S.Elia Hospital, Caltanissetta, Italy.
    The Role of Inflammation in Cardiovascular Disease2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 21, article id 12906Article, review/survey (Refereed)
    Abstract [en]

    Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1β, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.

    Download full text (pdf)
    fulltext
  • 17.
    Hudhud, Lina
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Department of Pharmacology and Pharmacotherapy, Center for Neuroscience, Medical School, University of Pécs, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary.
    Rozmer, Katalin
    Department of Pharmacology and Pharmacotherapy, Center for Neuroscience, Medical School, University of Pécs, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary; Department of Pharmaceutical Chemistry, University of Pécs, Pécs, Hungary; Hungarian Research Network, Chronic Pain Research Group, Pécs, Hungary.
    Kecskés, Angéla
    Department of Pharmacology and Pharmacotherapy, Center for Neuroscience, Medical School, University of Pécs, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary.
    Pohóczky, Krisztina
    Department of Pharmacology and Pharmacotherapy, Center for Neuroscience, Medical School, University of Pécs, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary; Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Pécs, Hungary.
    Bencze, Noémi
    Department of Pharmacology and Pharmacotherapy, Center for Neuroscience, Medical School, University of Pécs, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary.
    Buzás, Krisztina
    Department of Immunology, Albert Szent-Györgyi Medical School, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary; Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network (ELKH), Szeged, Hungary.
    Szőke, Éva
    Department of Pharmacology and Pharmacotherapy, Center for Neuroscience, Medical School, University of Pécs, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary; Hungarian Research Network, Chronic Pain Research Group, Pécs, Hungary.
    Helyes, Zsuzsanna
    Department of Pharmacology and Pharmacotherapy, Center for Neuroscience, Medical School, University of Pécs, Pécs, Hungary; National Laboratory for Drug Research and Development, Budapest, Hungary; Hungarian Research Network, Chronic Pain Research Group, Pécs, Hungary; PharmInVivo Ltd., Pécs, Hungary.
    Transient receptor potential Ankyrin 1 Ion channel is expressed in Osteosarcoma and its activation reduces viability2024In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, no 7, article id 3760Article in journal (Refereed)
    Abstract [en]

    Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive 45Ca2+ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant 45Ca2+ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate 45Ca2+ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC50 values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives.

    Download full text (pdf)
    fulltext
  • 18.
    Ibrahimi, Pranvera
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Jashari, Fisnik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ultrasound assessment of carotid plaque echogenicity response to statin therapy: a systematic review and meta-analysis2015In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 16, no 5, p. 10734-10747Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound.

    METHODS: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS).

    RESULTS: Nine out of 580 identified studies including 566 patients' carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%-36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months.

    CONCLUSIONS: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL.

    Download full text (pdf)
    fulltext
  • 19. Imran, Qari Muhammad
    et al.
    Lee, Sang-Uk
    Mun, Bong-Gyu
    Hussain, Adil
    Asaf, Sajjad
    Lee, In-Jung
    Yun, Byung-Wook
    WRKYs, the Jack-of-various-Trades, Modulate Dehydration Stress in Populus davidiana-A Transcriptomic Approach2019In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 20, no 2Article in journal (Refereed)
    Abstract [en]

    Populus davidiana, native to Korea and central Asian countries, is a major contributor to the Korean forest cover. In the current study, using high-throughput RNA-seq mediated transcriptome analysis, we identified about 87 P. davidiana WRKY transcription factors (PopdaWRKY TFs) that showed differential expression to dehydration stress in both sensitive and tolerant cultivars. Our results suggested that, on average, most of the WRKY genes were upregulated in tolerant cultivars but downregulated in sensitive cultivars. Based on protein sequence alignment, P. davidiana WRKYs were classified into three major groups, I, II, III, and further subgroups. Phylogenetic analysis showed that WRKY TFs and their orthologs in Arabidopsis and rice were clustered together in the same subgroups, suggesting similar functions across species. Significant correlation was found among qRT-PCR and RNA-seq analysis. In vivo analysis using model plant Arabidopsis showed that atwrky62 (orthologous to Potri.016G137900) knockout mutants were significantly sensitive to dehydration possibly due to an inability to close their stomata under dehydration conditions. In addition, a concomitant decrease in expression of ABA biosynthetic genes was observed. The AtHK1 that regulates stomatal movement was also downregulated in atwrky62 compared to the wild type. Taken together, our findings suggest a regulatory role of PopdaWRKYs under dehydration stress.

  • 20.
    Ismail, Hager
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
    AbdelMageed, Manar
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
    Lindmark, Gudrun
    Institution of Clinical Sciences, Lund University, Helsingborg, Sweden.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Prognostic Significance of GPR55 mRNA Expression in Colon Cancer2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 9, article id 4556Article in journal (Refereed)
    Abstract [en]

    G protein-coupled receptor 55 (GPR55) probably plays a role in innate immunity and tumor immunosurveillance through its effect on immune cells, such as T cells and NK cells. In this study, the prognostic value of GPR55 in colon cancer (CC) was investigated. mRNA expression levels of GPR55 were determined in 382 regional lymph nodes of 121 CC patients with 12 years observation time after curative surgery. The same clinical material had previously been analyzed for expression levels of CEA, CXCL16, CXCL17, GPR35 V2/3 and LGR5 mRNAs. Clinical cutoffs of 0.1365 copies/18S rRNA unit for GPR55 and 0.1481 for the GPR55/CEA ratio were applied to differentiate between the high-and low-GPR55 expression groups. Kaplan–Meier survival analysis and Cox regression risk analysis were used to determine prognostic value. Improved discrimination between the two groups was achieved by combining GPR55 with CEA, CXCL16 or CXCL17 compared with GPR55 alone. The best result was obtained using the GPR55/CEA ratio, with an increased mean survival time of 14 and 33 months at 5 and 12 years observation time, respectively (p = 0.0003 and p = 0.003) for the high-GPR55/CEA group. The explanation for the observed improvement is most likely that GPR55 is a marker for T cells and B cells in lymph nodes, whereas CEA, CXCL16 and CXCL17, are markers for tumor cells of epithelial origin.

    Download full text (pdf)
    fulltext
  • 21.
    Jashari, Fisnik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ahlqvist, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Garoff, Maria
    Umeå University, Faculty of Medicine, Department of Odontology.
    Jäghagen, Eva Levring
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Atherosclerotic Calcification Detection: A Comparative Study of Carotid Ultrasound and Cone Beam CT2015In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 16, no 8, p. 19978-19988Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIM: Arterial calcification is often detected on ultrasound examination but its diagnostic accuracy is not well validated. The aim of this study was to determine the accuracy of carotid ultrasound B mode findings in detecting atherosclerotic calcification quantified by cone beam computed tomography (CBCT).

    METHODS: We analyzed 94 carotid arteries, from 88 patients (mean age 70 ± 7 years, 33% females), who underwent pre-endarterectomy ultrasound examination. Plaques with high echogenic nodules and posterior shadowing were considered calcified. After surgery, the excised plaques were examined using CBCT, from which the calcification volume (mm3) was calculated. In cases with multiple calcifications the largest calcification nodule volume was used to represent the plaque. Carotid artery calcification by the two imaging techniques was compared using conventional correlations.

    RESULTS: Carotid ultrasound was highly accurate in detecting the presence of calcification; with a sensitivity of 88.2%. Based on the quartile ranges of calcification volumes measured by CBCT we have divided plaque calcification into four groups: <8; 8-35; 36-70 and >70 mm3. Calcification volumes ≥8 were accurately detectable by ultrasound with a sensitivity of 96%. Of the 21 plaques with <8 mm3 calcification volume; only 13 were detected by ultrasound; resulting in a sensitivity of 62%. There was no difference in the volume of calcification between symptomatic and asymptomatic patients.

    CONCLUSION: Carotid ultrasound is highly accurate in detecting the presence of calcified atherosclerotic lesions of volume ≥8 mm3; but less accurate in detecting smaller volume calcified plaques. Further development of ultrasound techniques should allow better detection of early arterial calcification.

    Download full text (pdf)
    fulltext
  • 22.
    Johansson, Emil
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Caraballo, Remi
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hurdiss, Daniel L.
    Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
    Mistry, Nitesh
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Andersson, C. David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Thompson, Rebecca F.
    Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
    Ranson, Neil A.
    Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
    Zocher, Georg
    Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
    Stehle, Thilo
    Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany; Department of Pediatrics, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Exploring the effect of structure-based scaffold hopping on the inhibition of coxsackievirus a24v transduction by pentavalent n-acetylneuraminic acid conjugates2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 16, article id 8418Article in journal (Refereed)
    Abstract [en]

    Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the disease over the last decades, thus affecting millions of individuals throughout the world. To date, no antiviral agents or vaccines are available for combating this disease, and treatment is mainly supportive. CVA24v utilizes Neu5Ac-containing glycans as attachment receptors facilitating entry into host cells. We have previously reported that pentavalent Neu5Ac conjugates based on a glucose-scaffold inhibit CVA24v infection of human corneal epithelial cells. In this study, we report on the design and synthesis of scaffold-replaced pentavalent Neu5Ac conjugates and their effect on CVA24v cell transduction and the use of cryogenic electron microscopy (cryo-EM) to study the binding of these multivalent conjugates to CVA24v. The results presented here provide insights into the development of Neu5Ac-based inhibitors of CVA24v and, most significantly, the first application of cryo-EM to study the binding of a multivalent ligand to a lectin.

    Download full text (pdf)
    fulltext
  • 23.
    Kaasinen, Mirjami
    et al.
    Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Hagström, Jaana
    Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Oral Pathology and Radiology, University of Turku, Turku, Finland; Translational Cancer Medicine Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Mustonen, Harri
    Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Translational Cancer Medicine Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Sorsa, Timo
    Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Section of Periodontology and Dental Prevention, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Solna, Sweden.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Haglund, Caj
    Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Translational Cancer Medicine Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Seppänen, Hanna
    Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Translational Cancer Medicine Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Matrix Metalloproteinase 8 Expression in a Tumour Predicts a Favourable Prognosis in Pancreatic Ductal Adenocarcinoma2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 6, article id 3314Article in journal (Refereed)
    Abstract [en]

    Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002–2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan–Meier analysis while uni-and multivariable analyses relied on the Cox proportional hazards model. A negative MMP-8 stain and elevated CRP level predicted a poor prognosis (hazard ratio [HR] = 6.95; 95% confidence interval (CI) 2.69–17.93; p < 0.001) compared to a positive stain and low CRP level (<10 mg/L). The absence of PMNs together with an elevated CRP level also predicted an unfavourable outcome (HR = 3.17; 95% CI 1.60–6.30; p = 0.001). MMP-8 expression in the tumour served as an independent positive prognostic factor (HR = 0.33; 95% CI 0.16–0.68; p = 0.003). Tumour MMP-8 expression and a low CRP level may predict a favourable outcome in PDAC with similar results for MMP-8-positive PMNs and low CRP levels. Tumoural MMP-8 expression represents an independent positive prognostic factor in PDAC.

    Download full text (pdf)
    fulltext
  • 24.
    Karaye, Kamilu M.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Yahaya, Isah A.
    Lindmark, Krister
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Serum Selenium and Ceruloplasmin in Nigerians with Peripartum Cardiomyopathy2015In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 16, no 4, p. 7644-7654Article in journal (Refereed)
    Abstract [en]

    The study aimed to determine if selenium deficiency, serum ceruloplasmin and traditional birth practices are risk factors for peripartum cardiomyopathy (PPCM), in Kano, Nigeria. This is a case-control study carried out in three hospitals, and PPCM patients were followed up for six months. Critically low serum selenium concentration was defined as <70 mu g/L. A total of 39 PPCM patients and 50 controls were consecutively recruited after satisfying the inclusion criteria. Mean serum selenium in patients (61.7 +/- 14.9 mu g/L) was significantly lower than in controls (118.4 +/- 45.6 mu g/L) (p < 0.001). The prevalence of serum selenium <70 mu g/L was significantly higher among patients (76.9%) than controls (22.0%) (p < 0.001). The mean ceruloplasmin and prevalence of socio-economic indices, multiparity, pregnancy-induced hypertension, obesity and twin pregnancy were not different between the groups (p > 0.05). Logistic regression showed that rural residency significantly increased the odds for serum selenium <70 mu g/L by 2.773-fold (p = 0.037). Baseline serum levels of selenium and ceruloplasmin were not associated with six-month mortality. This study has shown that selenium deficiency is a risk factor for PPCM in Kano, Nigeria, and is related to rural residency. However, serum ceruloplasmin, customary birth practices and some other characteristics were not associated with PPCM in the study area.

    Download full text (pdf)
    fulltext
  • 25.
    Kasho, Kazutoshi
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Krasauskas, Lukas
    Life Sciences Center, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
    Smirnovas, Vytautas
    Life Sciences Center, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
    Stojkovic, Gorazd
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Morozova-Roche, Ludmilla
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Wanrooij, Sjoerd
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Human polymerase δ-interacting protein 2 (Poldip2) inhibits the formation of human tau oligomers and fibrils2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 11, article id 5768Article in journal (Refereed)
    Abstract [en]

    A central characteristic of Alzheimer’s disease (AD) and other tauopathies is the accumulation of aggregated and misfolded Tau deposits in the brain. Tau-targeting therapies for AD have been unsuccessful in patients to date. Here we show that human polymerase δ-interacting protein 2 (PolDIP2) interacts with Tau. With a set of complementary methods, including thioflavin-T-based aggregation kinetic assays, Tau oligomer-specific dot-blot analysis, and single oligomer/fibril analysis by atomic force microscopy, we demonstrate that PolDIP2 inhibits Tau aggregation and amyloid fibril growth in vitro. The identification of PolDIP2 as a potential regulator of cellular Tau aggregation should be considered for future Tau-targeting therapeutics.

    Download full text (pdf)
    fulltext
  • 26.
    Kleczkowski, Leszek A.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Igamberdiev, Abir U.
    Department of Biology, Memorial University of Newfoundland, NL, St. John’s, Canada.
    Magnesium signaling in plants2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 3, article id 1159Article, review/survey (Refereed)
    Abstract [en]

    Free magnesium (Mg2+) is a signal of the adenylate (ATP+ADP+AMP) status in the cells. It results from the equilibrium of adenylate kinase (AK), which uses Mg-chelated and Mgfree adenylates as substrates in both directions of its reaction. The AK-mediated primary control of intracellular [Mg2+] is finely interwoven with the operation of membrane-bound adenylateand Mg2+-translocators, which in a given compartment control the supply of free adenylates and Mg2+ for the AK-mediated equilibration. As a result, [Mg2+] itself varies both between and within the compartments, depending on their energetic status and environmental clues. Other key nucleotide-utilizing/producing enzymes (e.g., nucleoside diphosphate kinase) may also be involved in fine-tuning of the intracellular [Mg2+]. Changes in [Mg2+] regulate activities of myriads of Mgutilizing/ requiring enzymes, affecting metabolism under both normal and stress conditions, and impacting photosynthetic performance, respiration, phloem loading and other processes. In compartments controlled by AK equilibrium (cytosol, chloroplasts, mitochondria, nucleus), the intracellular [Mg2+] can be calculated from total adenylate contents, based on the dependence of the apparent equilibrium constant of AK on [Mg2+]. Magnesium signaling, reflecting cellular adenylate status, is likely widespread in all eukaryotic and prokaryotic organisms, due simply to the omnipresent nature of AK and to its involvement in adenylate equilibration.

    Download full text (pdf)
    fulltext
  • 27.
    Kleczkowski, Leszek A.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Igamberdiev, Abir U.
    Department of Biology, Memorial University of Newfoundland, NL, St. John’s, Canada.
    Multiple roles of glycerate kinase—from photorespiration to gluconeogenesis, C4 metabolism, and plant immunity2024In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, no 6, article id 3258Article, review/survey (Refereed)
    Abstract [en]

    Plant glycerate kinase (GK) was previously considered an exclusively chloroplastic enzyme of the glycolate pathway (photorespiration), and its sole predicted role was to return most of the glycolate-derived carbon (as glycerate) to the Calvin cycle. However, recent discovery of cytosolic GK revealed metabolic links for glycerate to other processes. Although GK was initially proposed as being solely regulated by substrate availability, subsequent discoveries of its redox regulation and the light involvement in the production of chloroplastic and cytosolic GK isoforms have indicated a more refined regulation of the pathways of glycerate conversion. Here, we re-evaluate the importance of GK and emphasize its multifaceted role in plants. Thus, GK can be a major player in several branches of primary metabolism, including the glycolate pathway, gluconeogenesis, glycolysis, and C4 metabolism. In addition, recently, the chloroplastic (but not cytosolic) GK isoform was implicated as part of a light-dependent plant immune response to pathogen attack. The origins of glycerate are also discussed here; it is produced in several cell compartments and undergoes huge fluctuations depending on light/dark conditions. The recent discovery of the vacuolar glycerate transporter adds yet another layer to our understanding of glycerate transport/metabolism and that of other two- and three-carbon metabolites.

    Download full text (pdf)
    fulltext
  • 28.
    Koskinen Holm, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Engineering a 3D In Vitro Model of Human Gingival Tissue Equivalent with Genipin/Cytochalasin D2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 13, article id 7401Article in journal (Refereed)
    Abstract [en]

    Although three-dimensional (3D) co-culture of gingival keratinocytes and fibroblasts-populated collagen gel can mimic 3D structure of in vivo tissue, the uncontrolled contraction of collagen gel restricts its application in clinical and experimental practices. We here established a stable 3D gingival tissue equivalent (GTE) using hTERT-immortalized gingival fibroblasts (hGFBs)-populated collagen gel directly crosslinked with genipin/cytochalasin D and seeding hTERT-immortalized gingival keratinocytes (TIGKs) on the upper surface for a 2-week air–liquid interface co-culture. MTT assay was used to measure the cell viability of GTEs. GTE size was monitored following culture period, and the contraction was analyzed. Immunohistochemical assay was used to analyze GTE structure. qRT-PCR was conducted to examine the mRNA expression of keratinocyte-specific genes. Fifty µM genipin (G50) or combination (G + C) of G50 and 100 nM cytochalasin D significantly inhibited GTE contraction. Additionally, a higher cell viability appeared in GTEs crosslinked with G50 or G + C. GTEs crosslinked with genipin/cytochalasin D showed a distinct multilayered stratified epithelium that expressed keratinocyte-specific genes similar to native gingiva. Collagen directly crosslinked with G50 or G + C significantly reduced GTE contraction without damaging the epithelium. In summary, the TIGKs and hGFBs can successfully form organotypic multilayered cultures, which can be a valuable tool in the research regarding periodontal disease as well as oral mucosa disease. We conclude that genipin is a promising crosslinker with the ability to reduce collagen contraction while maintaining normal cell function in collagen-based oral tissue engineering.

    Download full text (pdf)
    fulltext
  • 29.
    Krüger, Nadine
    et al.
    Infection Biology Unit, German Primate Center, Göttingen, Germany.
    Rocha, Cheila
    Infection Biology Unit, German Primate Center, Göttingen, Germany.
    Runft, Sandra
    Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.
    Krüger, Johannes
    Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.
    Färber, Iris
    Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.
    Armando, Federico
    Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.
    Leitzen, Eva
    Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.
    Brogden, Graham
    Department of Biochemistry, University of Veterinary Medicine, Foundation, Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Foundation, Hannover, Germany; Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany.
    Gerold, Gisa
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Department of Biochemistry, University of Veterinary Medicine, Foundation, Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Foundation, Hannover, Germany; Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany.
    Pöhlmann, Stefan
    Infection Biology Unit, German Primate Center, Göttingen, Germany.
    Hoffmann, Markus
    Infection Biology Unit, German Primate Center, Göttingen, Germany.
    Baumgärtner, Wolfgang
    Department of Pathology, University of Veterinary Medicine, Foundation, Hannover, Germany.
    The upper respiratory tract of felids is highly susceptible to sars‐cov‐2 infection2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 19, article id 10636Article in journal (Refereed)
    Abstract [en]

    Natural or experimental infection of domestic cats and virus transmission from humans to captive predatory cats suggest that felids are highly susceptible to SARS‐CoV‐2 infection. However, it is unclear which cells and compartments of the respiratory tract are infected. To address this question, primary cell cultures derived from the nose, trachea, and lungs of cat and lion were inoculated with SARS‐CoV‐2. Strong viral replication was observed for nasal mucosa explants and tracheal air–liquid interface cultures, whereas replication in lung slices was less efficient. Infection was mainly restricted to epithelial cells and did not cause major pathological changes. Detection of high ACE2 levels in the nose and trachea but not lung further suggests that susceptibility of feline tissues to SARS‐CoV‐2 correlates with ACE2 expression. Collectively, this study demonstrates that SARS‐ CoV‐2 can efficiently replicate in the feline upper respiratory tract ex vivo and thus highlights the risk of SARS‐CoV‐2 spillover from humans to felids.

    Download full text (pdf)
    fulltext
  • 30.
    Kumar Gahlot, Dharmender
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). School of Biological Sciences, University of Reading, UK .
    Ifill, Gyles
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
    MacIntyre, Sheila
    School of Biological Sciences, University of Reading, UK.
    Optimised Heterologous Expression and Functional Analysis ofthe Yersinia pestis F1-Capsular Antigen Regulator Caf1R2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 18, article id 9805Article in journal (Refereed)
    Abstract [en]

    The bacterial pathogen, Yersinia pestis, has caused three historic pandemics and continuesto cause small outbreaks worldwide. During infection, Y. pestis assembles a capsule-like protectivecoat of thin fibres of Caf1 subunits. This F1 capsular antigen has attracted much attention due to itsclinical value in plague diagnostics and anti-plague vaccine development. Expression of F1 is tightlyregulated by a transcriptional activator, Caf1R, of the AraC/XylS family, proteins notoriously prone toaggregation. Here, we have optimised the recombinant expression of soluble Caf1R. Expression fromthe native and synthetic codon-optimised caf1R cloned in three different expression plasmids wasexamined in a library of E. coli host strains. The functionality of His-tagged Caf1R was demonstratedin vivo, but insolubility was a problem with overproduction. High levels of soluble MBP-Caf1R wereproduced from codon optimised caf1R. Transcriptional-lacZ reporter fusions defined the PM promoterand Caf1R binding site responsible for transcription of the cafMA1 operon. Use of the identifiedCaf1R binding caf DNA sequence in an electrophoretic mobility shift assay (EMSA) confirmed correctfolding and functionality of the Caf1R DNA-binding domain in recombinant MBP-Caf1R. Availabilityof functional recombinant Caf1R will be a valuable tool to elucidate control of expression of F1 andCaf1R-regulated pathophysiology of Y. pestis.

    Download full text (pdf)
    fulltext
    Download full text (pdf)
    Supplementary material
  • 31.
    Kumar Gahlot, Dharmender
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). School of Biological Sciences, University of Reading, Reading, UK.
    Taheri, Nayyer
    APC Microbiome Institute, University College Cork, Cork, Ireland.
    MacIntyre, Sheila
    School of Biological Sciences, University of Reading, Reading, UK.
    Diversity in genetic regulation of bacterial fimbriae assembled by the chaperone usher pathway2023In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, no 1, article id 161Article, review/survey (Refereed)
    Abstract [en]

    Bacteria express different types of hair-like proteinaceous appendages on their cell surface known as pili or fimbriae. These filamentous structures are primarily involved in the adherence of bacteria to both abiotic and biotic surfaces for biofilm formation and/or virulence of non-pathogenic and pathogenic bacteria. In pathogenic bacteria, especially Gram-negative bacteria, fimbriae play a key role in bacteria–host interactions which are critical for bacterial invasion and infection. Fimbriae assembled by the Chaperone Usher pathway (CUP) are widespread within the Enterobacteriaceae, and their expression is tightly regulated by specific environmental stimuli. Genes essential for expression of CUP fimbriae are organised in small blocks/clusters, which are often located in proximity to other virulence genes on a pathogenicity island. Since these surface appendages play a crucial role in bacterial virulence, they have potential to be harnessed in vaccine development. This review covers the regulation of expression of CUP-assembled fimbriae in Gram-negative bacteria and uses selected examples to demonstrate both dedicated and global regulatory mechanisms.

    Download full text (pdf)
    fulltext
  • 32.
    Kumar Kuna, Vijay
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lundgren, André
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Anerillas, Luis Oliveros
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Odontology.
    Brohlin, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Novikova, Ludmila N.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Andersson, Gustav
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Novikov, Lev N.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Efficacy of Nerve-Derived Hydrogels to Promote Axon Regeneration Is Influenced by the Method of Tissue Decellularization2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 15, article id 8746Article in journal (Refereed)
    Abstract [en]

    Injuries to large peripheral nerves are often associated with tissue defects and require reconstruction using autologous nerve grafts, which have limited availability and result in donor site morbidity. Peripheral nerve-derived hydrogels could potentially supplement or even replace these grafts. In this study, three decellularization protocols based on the ionic detergents sodium dodecyl sulfate (P1) and sodium deoxycholate (P2), or the organic solvent tri-n-butyl phosphate (P3), were used to prepare hydrogels. All protocols resulted in significantly decreased amounts of genomic DNA, but the P2 hydrogel showed the best preservation of extracellular matrix proteins, cytokines, and chemokines, and reduced levels of sulfated glycosaminoglycans. In vitro P1 and P2 hydrogels supported Schwann cell viability, secretion of VEGF, and neurite outgrowth. Surgical repair of a 10 mm-long rat sciatic nerve gap was performed by implantation of tubular polycaprolactone conduits filled with hydrogels followed by analyses using diffusion tensor imaging and immunostaining for neuronal and glial markers. The results demonstrated that the P2 hydrogel considerably increased the number of axons and the distance of regeneration into the distal nerve stump. In summary, the method used to decellularize nerve tissue affects the efficacy of the resulting hydrogels to support regeneration after nerve injury.

    Download full text (pdf)
    fulltext
  • 33.
    Kurepin, Leonid V.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Dahal, Keshav P.
    Savitch, Leonid V.
    Singh, Jas
    Bode, Rainer
    Ivanov, Alexander G.
    Hurry, Vaughan
    Huener, Norman P. A.
    Role of CBFs as Integrators of Chloroplast Redox, Phytochrome and Plant Hormone Signaling during Cold Acclimation2013In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 14, no 6, p. 12729-12763Article, review/survey (Refereed)
    Abstract [en]

    Cold acclimation of winter cereals and other winter hardy species is a prerequisite to increase subsequent freezing tolerance. Low temperatures upregulate the expression of C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB1) which in turn induce the expression of COLD-REGULATED (COR) genes. We summarize evidence which indicates that the integration of these interactions is responsible for the dwarf phenotype and enhanced photosynthetic performance associated with cold-acclimated and CBF-overexpressing plants. Plants overexpressing CBFs but grown at warm temperatures mimic the cold-tolerant, dwarf, compact phenotype; increased photosynthetic performance; and biomass accumulation typically associated with cold-acclimated plants. In this review, we propose a model whereby the cold acclimation signal is perceived by plants through an integration of low temperature and changes in light intensity, as well as changes in light quality. Such integration leads to the activation of the CBF-regulon and subsequent upregulation of COR gene and GA 2-oxidase (GA2ox) expression which results in a dwarf phenotype coupled with increased freezing tolerance and enhanced photosynthetic performance. We conclude that, due to their photoautotrophic nature, plants do not rely on a single low temperature sensor, but integrate changes in light intensity, light quality, and membrane viscosity in order to establish the cold-acclimated state. CBFs appear to act as master regulators of these interconnecting sensing/signaling pathways.

    Download full text (pdf)
    fulltext
  • 34.
    Lakehal, Abdellah
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Dob, Asma
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Novak, Ondrej
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Forest Genetics and Physiology, Swedish Agriculture University, Umea, Sweden.
    Bellini, Catherine
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Institut Jean-Pierre Bourgin, INRA, AgroParisTech, CNRS, Université Paris-Saclay, Versailles, France.
    A DAO1-Mediated Circuit Controls Auxin and Jasmonate Crosstalk Robustness during Adventitious Root Initiation in Arabidopsis2019In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 20, no 18, article id 4428Article in journal (Refereed)
    Abstract [en]

    Adventitious rooting is a post-embryonic developmental program governed by a multitude of endogenous and environmental cues. Auxin, along with other phytohormones, integrates and translates these cues into precise molecular signatures to provide a coherent developmental output. Auxin signaling guides every step of adventitious root (AR) development from the early event of cell reprogramming and identity transitions until emergence. We have previously shown that auxin signaling controls the early events of AR initiation (ARI) by modulating the homeostasis of the negative regulator jasmonate (JA). Although considerable knowledge has been acquired about the role of auxin and JA in ARI, the genetic components acting downstream of JA signaling and the mechanistic basis controlling the interaction between these two hormones are not well understood. Here we provide evidence that COI1-dependent JA signaling controls the expression of DAO1 and its closely related paralog DAO2. In addition, we show that the dao1-1 loss of function mutant produces more ARs than the wild type, probably due to its deficiency in accumulating JA and its bioactive metabolite JA-Ile. Together, our data indicate that DAO1 controls a sensitive feedback circuit that stabilizes the auxin and JA crosstalk during ARI.

    Download full text (pdf)
    fulltext
  • 35.
    Lammi, Mikko
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning, Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi'an Jiaotong University, Xi'an, China.
    Piltti, Juha
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Nordlab Kokkola, Keski-Pohjanmaa Central Hospital Soite, Kokkola, Finland.
    Prittinen, Juha
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Challenges in fabrication of tissue-engineered cartilage with correct cellular colonization and extracellular matrix assembly2018In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 19, no 9, article id 2700Article, review/survey (Refereed)
    Abstract [en]

    A correct articular cartilage ultrastructure regarding its structural components and cellularity is important for appropriate performance of tissue-engineered articular cartilage. Various scaffold-based, as well as scaffold-free, culture models have been under development to manufacture functional cartilage tissue. Even decellularized tissues have been considered as a potential choice for cellular seeding and tissue fabrication. Pore size, interconnectivity, and functionalization of the scaffold architecture can be varied. Increased mechanical function requires a dense scaffold, which also easily restricts cellular access within the scaffold at seeding. High pore size enhances nutrient transport, while small pore size improves cellular interactions and scaffold resorption. In scaffold-free cultures, the cells assemble the tissue completely by themselves; in optimized cultures, they should be able to fabricate native-like tissue. Decellularized cartilage has a native ultrastructure, although it is a challenge to obtain proper cellular colonization during cell seeding. Bioprinting can, in principle, provide the tissue with correct cellularity and extracellular matrix content, although it is still an open question as to how the correct molecular interaction and structure of extracellular matrix could be achieved. These are challenges facing the ongoing efforts to manufacture optimal articular cartilage.

    Download full text (pdf)
    fulltext
  • 36.
    Lammi, Mikko
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning, Institute of Endemic Diseases, School of Public Health of Health Science Center, Xi’an Jiaotong University, Xi’an, China.
    Qu, Chengjuan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Selenium-related transcriptional regulation of gene expression2018In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 19, no 9, article id 2665Article, review/survey (Refereed)
    Abstract [en]

    The selenium content of the body is known to control the expression levels of numerous genes, both so-called selenoproteins and non-selenoproteins. Selenium is a trace element essential to human health, and its deficiency is related to, for instance, cardiovascular and myodegenerative diseases, infertility and osteochondropathy called Kashin⁻Beck disease. It is incorporated as selenocysteine to the selenoproteins, which protect against reactive oxygen and nitrogen species. They also participate in the activation of the thyroid hormone, and play a role in immune system functioning. The synthesis and incorporation of selenocysteine occurs via a special mechanism, which differs from the one used for standard amino acids. The codon for selenocysteine is a regular in-frame stop codon, which can be passed by a specific complex machinery participating in translation elongation and termination. This includes a presence of selenocysteine insertion sequence (SECIS) in the 3'-untranslated part of the selenoprotein mRNAs. Nonsense-mediated decay is involved in the regulation of the selenoprotein mRNA levels, but other mechanisms are also possible. Recent transcriptional analyses of messenger RNAs, microRNAs and long non-coding RNAs combined with proteomic data of samples from Keshan and Kashin⁻Beck disease patients have identified new possible cellular pathways related to transcriptional regulation by selenium.

    Download full text (pdf)
    fulltext
  • 37.
    Landfors, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Vikström, Simon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Leukotriene A4 Hydrolase and Hepatocyte Growth Factor Are Risk Factors of Sudden Cardiac Death Due to First-Ever Myocardial Infarction2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 18, article id 10251Article in journal (Refereed)
    Abstract [en]

    Patients at a high risk for sudden cardiac death (SCD) without previous history of cardiovascular disease remain a challenge to identify. Atherosclerosis and prothrombotic states involve inflammation and non-cardiac tissue damage that may play active roles in SCD development. Therefore, we hypothesized that circulating proteins implicated in inflammation and tissue damage are linked to the future risk of SCD. We conducted a prospective nested case–control study of SCD cases with verified myocardial infarction (N = 224) and matched controls without myocardial infarction (N = 224), aged 60 ± 10 years time and median time to event was 8 years. Protein concentrations (N = 122) were measured using a proximity extension immunoassay. The analyses revealed 14 proteins significantly associated with an increased risk of SCD, from which two remained significant after adjusting for smoking status, systolic blood pressure, BMI, cholesterol, and glucose levels. We identified leukotriene A4 hydrolase (LTA4H, odds ratio 1.80, corrected confidence interval (CIcorr) 1.02–3.17) and hepatocyte growth factor (HGF; odds ratio 1.81, CIcorr 1.06–3.11) as independent risk markers of SCD. Elevated LTA4H may reflect increased systemic and pulmonary neutrophilic inflammatory processes that can contribute to atherosclerotic plaque instability. Increased HGF levels are linked to obesity-related metabolic disturbances that are more prevalent in SCD cases than the controls.

    Download full text (pdf)
    fulltext
  • 38.
    Lascu, Irina
    et al.
    Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
    Tănase, Ana Maria
    Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
    Jablonski, Piotr
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Chiciudean, Iulia
    Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
    Preda, Maria Irina
    Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
    Avramescu, Sorin
    Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, Bucharest, Romania.
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Stoica, Ileana
    Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
    Revealing the phenotypic and genomic background for pha production from rapeseed-biodiesel crude glycerol using photobacterium ganghwense C2.22022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 22, article id 13754Article in journal (Refereed)
    Abstract [en]

    Polyhydroxyalkanoates (PHA) are promising biodegradable and biocompatible bioplastics, and extensive knowledge of the employed bacterial strain’s metabolic capabilities is necessary in choosing economically feasible production conditions. This study aimed to create an in-depth view of the utilization of Photobacterium ganghwense C2.2 for PHA production by linking a wide array of characterization methods: metabolic pathway annotation from the strain’s complete genome, high-throughput phenotypic tests, and biomass analyses through plate-based assays and flask and bioreactor cultivations. We confirmed, in PHA production conditions, urea catabolization, fatty acid degradation and synthesis, and high pH variation and osmotic stress tolerance. With urea as a nitrogen source, pure and rapeseed-biodiesel crude glycerol were analyzed comparatively as carbon sources for fermentation at 20 °C. Flask cultivations yielded 2.2 g/L and 2 g/L PHA at 120 h, respectively, with molecular weights of 428,629 g/mol and 81,515 g/mol. Bioreactor batch cultivation doubled biomass accumulation (10 g/L and 13.2 g/L) in 48 h, with a PHA productivity of 0.133 g/(L·h) and 0.05 g/(L·h). Thus, phenotypic and genomic analyses determined the successful use of Photobacterium ganghwense C2.2 for PHA production using urea and crude glycerol and 20 g/L NaCl, without pH adjustment, providing the basis for a viable fermentation process.

    Download full text (pdf)
    fulltext
  • 39. Legler, Juliette
    et al.
    Zalko, Daniel
    Jourdan, Fabien
    Jacobs, Miriam
    Fromenty, Bernard
    Balaguer, Patrick
    Bourguet, William
    Kos, Vesna Munic
    Nadal, Angel
    Beausoleil, Claire
    Cristobal, Susana
    Remy, Sylvie
    Ermler, Sibylle
    Margiotta-Casaluci, Luigi
    Griffin, Julian L.
    Blumberg, Bruce
    Chesne, Christophe
    Hoffmann, Sebastian
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kamstra, Jorke H.
    The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds2020In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 21, no 10, article id 3480Article in journal (Refereed)
    Abstract [en]

    The purpose of this project report is to introduce the European "GOLIATH" project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as "metabolism disrupting compounds" (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world's first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption-hepatocytes, pancreatic endocrine cells, myocytes and adipocytes-and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.

    Download full text (pdf)
    fulltext
  • 40.
    Liu, Li
    et al.
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Liu, Huan
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Meng, Peilin
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Zhang, Yanan
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China; School of Nursing, Lanzhou University, Lanzhou, China.
    Zhang, Feng'e
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Jia, Yumeng
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Cheng, Bolun
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Medical and Translational Biology. School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Zhang, Feng
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Guo, Xiong
    School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
    Involvement of yes-associated protein 1 activation in the matrix degradation of human-induced-pluripotent-stem-cell-derived chondrocytes induced by T-2 toxin and deoxynivalenol alone and in combination2024In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, no 2, article id 878Article in journal (Refereed)
    Abstract [en]

    T-2 toxin and deoxynivalenol (DON) are two prevalent mycotoxins that cause cartilage damage in Kashin-Beck disease (KBD). Cartilage extracellular matrix (ECM) degradation in chondrocytes is a significant pathological feature of KBD. It has been shown that the Hippo pathway is involved in cartilage ECM degradation. This study aimed to examine the effect of YAP, a major regulator of the Hippo pathway, on the ECM degradation in the hiPS-derived chondrocytes (hiPS-Ch) model of KBD. The hiPS-Ch injury models were established via treatment with T-2 toxin/DON alone or in combination. We found that T-2 toxin and DON inhibited the proliferation of hiPS-Ch in a dose-dependent manner; significantly increased the levels of YAP, SOX9, and MMP13; and decreased the levels of COL2A1 and ACAN (all p values < 0.05). Immunofluorescence revealed that YAP was primarily located in the nuclei of hiPS-Ch, and its expression level increased with toxin concentrations. The inhibition of YAP resulted in the dysregulated expression of chondrogenic markers (all p values < 0.05). These findings suggest that T-2 toxin and DON may inhibit the proliferation of, and induce the ECM degradation, of hiPS-Ch mediated by YAP, providing further insight into the cellular and molecular mechanisms contributing to cartilage damage caused by toxins.

    Download full text (pdf)
    fulltext
  • 41.
    Lundwall, Åke
    et al.
    Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Bovinder Ylitalo, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Klk4t2 is a hormonally regulated transcript from the klk4 locus2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 23, article id 13023Article in journal (Refereed)
    Abstract [en]

    The human kallikrein-related peptidase 4 (KLK4) and the transcribed pseudogene KLKP1 are reported to be highly expressed in the prostate. When trying to clone transcripts of KLKP1, we partly failed. Instead, we identified an androgen-regulated transcript, KLK4T2, which appeared to be a splice variant of KLK4 that also contained exons of KLKP1. Expression analysis of KLK4, KLK4T2, and KLKP1 transcripts in prostate cancer cell lines showed high levels of KLKP1 transcripts in the nucleus and in unfractionated cell extract, whereas it was almost completely absent in the cytoplasmatic fraction. This was in contrast to KLK4 and KLK4T2, which displayed high to mod-erate levels in the cytoplasm. In patient cohorts we found significantly higher expression of both KLK4T2 and KLK4 in benign prostatic hyperplasia compared to both primary prostate cancer and bone metastasis. Analysis of tissue panels demonstrated the highest expression of KLK4T2 in the prostate, but in contrast to the classical KLK4, relatively high levels were also found in placenta. So far, the function of KLK4T2 is still to be explored, but the structure of the translation product indicated that it generates a 17.4 kDa intracellular protein with possible regulatory function.

    Download full text (pdf)
    fulltext
  • 42. Lupu, Diana
    et al.
    Andersson, Patrik L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bornehag, Carl-Gustaf
    Demeneix, Barbara
    Fritsche, Ellen
    Gennings, Chris
    Lichtensteiger, Walter
    Leist, Marcel
    Leonards, Pim E. G.
    Ponsonby, Anne-Louise
    Scholze, Martin
    Testa, Giuseppe
    Tresguerres, Jesus A. E.
    Westerink, Remco H. S.
    Zalc, Bernard
    Ruegg, Joelle
    The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity2020In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 21, no 11, article id 3978Article in journal (Refereed)
    Abstract [en]

    Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.

    Download full text (pdf)
    fulltext
  • 43.
    Marek, Katarzyna
    et al.
    Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
    Armando, Federico
    Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
    Nippold, Vanessa Maria
    Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
    Rohn, Karl
    Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Hannover, Germany.
    Plattet, Philippe
    Division of Experimental Clinical Research, Vetsuisse University Bern, Bern, Switzerland.
    Brogden, Graham
    Department of Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany; Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany; Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany.
    Gerold, Gisa
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology. Department of Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany; Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
    Baumgärtner, Wolfgang
    Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
    Puff, Christina
    Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
    Persistent Infection of a Canine Histiocytic Sarcoma Cell Line with Attenuated Canine Distemper Virus Expressing Vasostatin or Granulocyte-Macrophage Colony-Stimulating Factor2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 11, article id 6156Article in journal (Refereed)
    Abstract [en]

    Canine histiocytic sarcoma (HS) represents a neoplasia with poor prognosis. Due to the high metastatic rate of HS, there is urgency to improve treatment options and to prevent tumor metastases. Canine distemper virus (CDV) is a single-stranded negative-sense RNA (ssRNA (-)) virus with potentially oncolytic properties. Moreover, vasostatin and granulocyte-macrophage colony-stimulating factor (GM-CSF) are attractive molecules in cancer therapy research because of their anti-angiogenetic properties and potential modulation of the tumor microenvironment. In the present study, an in vitro characterization of two genetically engineered viruses based on the CDV strain Onderstepoort (CDV-Ond), CDV-Ondneon-vasostatin and CDV-Ondneon-GM-CSF was performed. Canine histiocytic sarcoma cells (DH82 cells) were persistently infected with CDV-Ond, CDV-Ondneon, CDV-Ondneon-vasostatin and CDV-Ondneon-GM-CSF and characterized on a molecular and protein level regarding their vasostatin and GM-CSF production. Interestingly, DH82 cells persistently infected with CDV-Ondneon-vasostatin showed a significantly increased number of vasostatin mRNA transcripts. Similarly, DH82 cells persistently infected with CDV-Ondneon-GM-CSF displayed an increased number of GM-CSF mRNA transcripts mirrored on the protein level as confirmed by immunofluorescence and Western blot. In summary, modified CDV-Ond strains expressed GM-CSF and vasostatin, rendering them promising candidates for the improvement of oncolytic virotherapies, which should be further detailed in future in vivo studies.

    Download full text (pdf)
    fulltext
  • 44.
    Mason, James E.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Lundberg, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nyström, Hanna
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Surgery, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    A cross-sectional and longitudinal analysis of pre-diagnostic blood plasma biomarkers for early detection of pancreatic cancer2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 21, article id 12969Article in journal (Refereed)
    Abstract [en]

    Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC.

    Download full text (pdf)
    fulltext
  • 45.
    Miles, Lindsey A.
    et al.
    Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United States.
    Ny, Lina
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Pietrzykowska, Malgorzata
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Shen, Yue
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Parmer, Robert J.
    Department of Medicine, University of California San Diego, La Jolla, CA, United States; Veterans Administration San Diego Healthcare System, CA, San Diego, United States.
    Plasminogen receptors and fibrinolysis2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 4, p. 1-12, article id 1712Article, review/survey (Refereed)
    Abstract [en]

    The ability of cells to promote plasminogen activation on their surfaces is now well recognized, and several distinct cell surface proteins have been demonstrated to function as plasminogen receptors. Here, we review studies demonstrating that plasminogen bound to cells, in addition to plasminogen directly bound to fibrin, plays a major role in regulating fibrin surveillance. We focus on the ability of specific plasminogen receptors on eukaryotic cells to promote fibrinolysis in the in vivo setting by reviewing data obtained predominantly in murine models. Roles for distinct plasminogen receptors in fibrin surveillance in intravascular fibrinolysis, immune cell recruitment in the inflammatory response, wound healing, and lactational development are discussed.

    Download full text (pdf)
    fulltext
  • 46.
    Mishra, Laxmi S.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Funk, Christiane
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    The FtsHi enzymes of Arabidopsis thaliana: pseudo-proteases with an important function2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 11, article id 5917Article in journal (Refereed)
    Abstract [en]

    FtsH metalloproteases found in eubacteria, animals, and plants are well-known for their vital role in the maintenance and proteolysis of membrane proteins. Their location is restricted to organelles of endosymbiotic origin, the chloroplasts, and mitochondria. In the model organism Arabidopsis thaliana, there are 17 membrane-bound FtsH proteases containing an AAA+ (ATPase associated with various cellular activities) and a Zn2+ metalloprotease domain. However, in five of those, the zinc-binding motif HEXXH is either mutated (FtsHi1, 2, 4, 5) or completely missing (FtsHi3), rendering these enzymes presumably inactive in proteolysis. Still, homozygous null mutants of the pseudo-proteases FtsHi1, 2, 4, 5 are embryo-lethal. Homozygous ftshi3 or a weak point mutant in FTSHi1 are affected in overall plant growth and development. This review will focus on the findings concerning the FtsHi pseudo-proteases and their involvement in protein import, leading to consequences in embryogenesis, seed growth, chloroplast, and leaf development and oxidative stress management.

    Download full text (pdf)
    fulltext
  • 47.
    Muthu, Magesh
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Nordström, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Current Status and Future Prospects of Clinically Exploiting Cancer-specific Metabolism: Why Is Tumor Metabolism Not More Extensively Translated into Clinical Targets and Biomarkers?2019In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 20, no 6, article id 1385Article, review/survey (Refereed)
    Abstract [en]

    Tumor cells exhibit a specialized metabolism supporting their superior ability for rapid proliferation, migration, and apoptotic evasion. It is reasonable to assume that the specific metabolic needs of the tumor cells can offer an array of therapeutic windows as pharmacological disturbance may derail the biochemical mechanisms necessary for maintaining the tumor characteristics, while being less important for normally proliferating cells. In addition, the specialized metabolism may leave a unique metabolic signature which could be used clinically for diagnostic or prognostic purposes. Quantitative global metabolic profiling (metabolomics) has evolved over the last two decades. However, despite the technology's present ability to measure 1000s of endogenous metabolites in various clinical or biological specimens, there are essentially no examples of metabolomics investigations being translated into actual utility in the cancer clinic. This review investigates the current efforts of using metabolomics as a tool for translation of tumor metabolism into the clinic and further seeks to outline paths for increasing the momentum of using tumor metabolism as a biomarker and drug target opportunity.

    Download full text (pdf)
    fulltext
  • 48.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Caloric Restriction and Its Effect on Blood Pressure, Heart Rate Variability and Arterial Stiffness and Dilatation: A Review of the Evidence2018In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 19, no 3, article id 751Article, review/survey (Refereed)
    Abstract [en]

    Essential hypertension, fast heart rate, low heart rate variability, sympathetic nervous system dominance over parasympathetic, arterial stiffness, endothelial dysfunction and poor flow-mediated arterial dilatation are all associated with cardiovascular mortality and morbidity. This review of randomised controlled trials and other studies demonstrates that caloric restriction (CR) is capable of significantly improving all these parameters, normalising blood pressure (BP) and allowing patients to discontinue antihypertensive medication, while never becoming hypotensive. CR appears to be effective regardless of age, gender, ethnicity, weight, body mass index (BMI) or a diagnosis of metabolic syndrome or type 2 diabetes, but the greatest benefit is usually observed in the sickest subjects and BP may continue to improve during the refeeding period. Exercise enhances the effects of CR only in hypertensive subjects. There is as yet no consensus on the mechanism of effect of CR and it may be multifactorial. Several studies have suggested that improvement in BP is related to improvement in insulin sensitivity, as well as increased nitric oxide production through improved endothelial function. In addition, CR is known to induce SIRT1, a nutrient sensor, which is linked to a number of beneficial effects in the body.

    Download full text (pdf)
    fulltext
  • 49.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Howard, John McLaren
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    A Review of the Effect of Diet on Cardiovascular Calcification2015In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 16, no 4, p. 8861-8883Article, review/survey (Refereed)
    Abstract [en]

    Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain -3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 g/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (380 mg/day) and phylloquinone (500 g/day) proved protective, as did a serum 25(OH)D concentration of 75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of -tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 mu mol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification.

    Download full text (pdf)
    fulltext
  • 50.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhao, Ying
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Diabetes and Hypertension Consistently Predict the Presence and Extent of Coronary Artery Calcification in Symptomatic Patients: A Systematic Review and Meta-Analysis2016In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 17, no 9, article id 1481Article, review/survey (Refereed)
    Abstract [en]

    Background: The relationship of conventional cardiovascular risk factors (age, gender, ethnicity, diabetes, dyslipidaemia, hypertension, obesity, exercise, and the number of risk factors) to coronary artery calcification (CAC) presence and extent has never before been assessed in a systematic review and meta-analysis.

    Methods: We included only English language studies that assessed at least three conventional risk factors apart from age, gender, and ethnicity, but excluded studies in which all patients had another confirmed condition such as renal disease.

    Results: In total, 10 studies, comprising 15,769 patients, were investigated in the systematic review and seven studies, comprising 12,682 patients, were included in the meta-analysis, which demonstrated the importance of diabetes and hypertension as predictors of CAC presence and extent, with age also predicting CAC presence. Male gender, dyslipidaemia, family history of coronary artery disease, obesity, and smoking were overall not predictive of either CAC presence or extent, despite dyslipidaemia being a key risk factor for coronary artery disease (CAD).

    Conclusion: Diabetes and hypertension consistently predict the presence and extent of CAC in symptomatic patients.

     

    Download full text (pdf)
    fulltext
12 1 - 50 of 78
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • 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