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Kruse, Robert
Publications (10 of 24) Show all publications
Östling, H., Kruse, R., Helenius, G. & Lodefalk, M. (2019). Placental expression of microRNAs in infants born small for gestational age. Placenta, 81, 46-53
Open this publication in new window or tab >>Placental expression of microRNAs in infants born small for gestational age
2019 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 81, p. 46-53Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: The molecular mechanisms behind poor foetal growth are not fully known. The aim of this study was to explore global microRNA expression in placentas of infants born small for gestational age (SGA) compared to infants with a normal birth weight (NBW).

METHODS: Placental biopsies from term infants were identified in a biobank and divided into four groups: infants born SGA with (n = 13) or without (n = 9) exposure to low maternal gestational weight gain (GWG) and infants born with NBWs with (n = 20) or without (n = 26) exposure to low GWG. All women and infants were healthy, and no woman smoked during pregnancy. Only vaginal deliveries were included. Next-generation sequencing was performed with single read sequencing of >9 million reads per sample. Differential microRNA expression was analysed using ANOVA for unequal variances (Welch) with multiple testing corrections through the Benjamini-Hochberg method. A fold change >2 and a corrected p value < 0.05 were considered significant. Adjustments for possible confounding factors were made using a linear regression model.

RESULTS: A total of 1870 known, mature human microRNAs were detected in the sample. MiR-3679-5p and miR-193b-3p were significantly upregulated, and miR-379-3p, miR-335-3p, miR-4532, miR-519e-3p, miR-3065-5p, and miR-105-5p were significantly downregulated after adjustment for potential confounding factors in SGA infants with normal GWG compared to infants with NBWs and normal GWG.

DISCUSSION: Infants born unexplained SGA show differential microRNA expression in their placenta. Important pathways for the differentially expressed microRNAs include inflammation and the insulin-IGF system.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Foetal growth, Inflammation, Placenta, RNA-Sequencing, Small for gestational age, microRNA
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-74556 (URN)10.1016/j.placenta.2019.05.001 (DOI)000468874700007 ()31138431 (PubMedID)2-s2.0-85065481896 (Scopus ID)
Note

Funding Agency:

Research Committee of Region Örebro County and ALF funding Region Örebro County

Available from: 2019-06-05 Created: 2019-06-05 Last updated: 2019-06-14Bibliographically approved
Demirel, I., Persson, A., Brauner, A., Särndahl, E., Kruse, R. & Persson, K. (2018). Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells. Frontiers in Cellular and Infection Microbiology, 8, Article ID 81.
Open this publication in new window or tab >>Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells
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2018 (English)In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 8, article id 81Article in journal (Refereed) Published
Abstract [en]

The NLRP3 inflammasome and IL-1 beta release have recently been suggested to be important for the progression of urinary tract infection (UTI). However, much is still unknown regarding the interaction of UPEC and the NLRP3 inflammasome. The purpose of this study was to elucidate what virulence factors uropathogenic Escherichia coil (UPEC) use to modulate NLRP3 inflammasome activation and subsequent IL-1 beta release and the role of NLRP3 for UPEC colonization of bladder epithelial cells. The bladder epithelial cell line 5637, CRISPR/Cas9 generated NLRP3, caspase-1 and mesotrypsin deficient cell lines and transformed primary bladder epithelial cells (HBLAK) were stimulated with UPEC isolates and the non-pathogenic MG1655 strain. We found that the UPEC strain CFT073, but not MG1655, induced an increased caspase-1 activity and IL-1 beta release from bladder epithelial cells. The increase was shown to be mediated by et-hemolysin activation of the NLRP3 inflammasome in an NE-kappa B-independent manner. The effect of-hemolysin on IL-1 beta release was biphasic, initially suppressive, later inductive. Furthermore, the phase-locked type-1-fimbrial ON variant of CFT073 inhibited caspase-1 activation and IL-1 beta release. In addition, the ability of CFT073 to adhere to and invade NLRP3 deficient cells was significantly reduced compare to wild-type cells. The reduced colonization of NLRP3-deficient cells was type-1 fimbriae dependent. In conclusion, we found that the NLRP3 inflammasome was important for type-1 fimbriae-dependent colonization of bladder epithelial cells and that both type-1 fimbriae and alpha-hemolysin can modulate the activity of the NLRP3 inflammasome.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
UPEC, NLRP3 inflammasome, IL-1 beta, alpha-hemolysin, type-1 fimbriae
National Category
Immunology in the medical area Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-66388 (URN)10.3389/fcimb.2018.00081 (DOI)000427407100001 ()2-s2.0-85043771169 (Scopus ID)
Note

Funding Agency:

Faculty of Medicine and Health at Örebro University 

Available from: 2018-04-09 Created: 2018-04-09 Last updated: 2018-08-20Bibliographically approved
Welander, E., Åström, M., Enonge Fotabe, L., Kardeby, C., Tina, E., Elgbratt, K., . . . Ivarsson, M. (2018). Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis. In: : . Paper presented at Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018.
Open this publication in new window or tab >>Integrated analysis indicates reciprocal immune response dysregulations between bone marrow multipotent stromal cells and granulocytes at the mRNA but not at the protein level in myelofibrosis
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-69350 (URN)
Conference
Fortbildningsdagar i hematologi, Umeå, 3-5 Oktober, 2018
Available from: 2018-10-08 Created: 2018-10-08 Last updated: 2019-03-26Bibliographically approved
Bergemalm, D., Kruse, R., Sapnara, M., Halfvarson, J. & Hultgren Hörnquist, E. (2017). Elevated fecal peptidase D at onset of colitis in Galphai2(-/-) mice, a mouse model of IBD. PLoS ONE, 12(3), Article ID e0174275.
Open this publication in new window or tab >>Elevated fecal peptidase D at onset of colitis in Galphai2(-/-) mice, a mouse model of IBD
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174275Article in journal (Refereed) Published
Abstract [en]

Background: The identification of novel fecal biomarkers in inflammatory bowel disease (IBD) is hampered by the complexity of the human fecal proteome. On the other hand, in experimental mouse models there is probably less variation. We investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms.

Methods: Fecal samples were collected at onset of inflammation in Galphai2(-/-) mice, a well-described spontaneous model of chronic colitis, and from healthy littermates. The fecal proteome was analyzed by two-dimensional electrophoresis and quantitative mass spectrometry and results were then validated in a new cohort of mice.

Results: As a potential top marker of disease, peptidase D was found at a higher ratio in Galphai24mouse feces relative to controls (fold change 27; p = 0.019). Other proteins found to be enriched in Gai2(-/-) mice were mainly pancreatic proteases, and proteins from plasma and blood cells. A tendency of increased calprotectin, subunit S100-A8, was also observed (fold change 21; p = 0.058). Proteases are potential activators of inflammation in the gastrointestinal tract through their interaction with the proteinase-activated receptor 2 (PAR2). Accordingly, the level of PAR2 was found to be elevated in both the colon and the pancreas of Galphai24- mice at different stages of disease.

Conclusions: These findings identify peptidase D, an ubiquitously expressed intracellular peptidase, as a potential novel marker of colitis. The elevated levels of fecal proteases may be involved in the pathogenesis of colitis and contribute to the clinical phenotype, possibly by activation of intestinal PAR2.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-57622 (URN)10.1371/journal.pone.0174275 (DOI)000399089000082 ()28323866 (PubMedID)2-s2.0-85016065409 (Scopus ID)
Note

Funding Agencies:

Bengt lhre research foundation  

Region Örebro county  OLL-526131 

Available from: 2017-05-10 Created: 2017-05-10 Last updated: 2018-07-31Bibliographically approved
Bang, C. S., Demirel, I., Kruse, R. & Persson, K. (2017). Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli. PLoS ONE, 12(6), Article ID e0178541.
Open this publication in new window or tab >>Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli
2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0178541Article in journal (Refereed) Published
Abstract [en]

Treatment of urinary tract infections is today a challenge due to the increasing prevalence of multidrug-resistant ESBL-producing uropathogenic Escherichia coli (UPEC). There is an urgent need for new treatment strategies for multidrug-resistant UPEC and preferably with targets that have low potential for development of resistance. Carbon monoxide-releasing molecules (CORMs) are novel and potent antibacterial agents. The present study examines the transcriptomic targets of CORM-2 in a multidrug-resistant ESBL-producing UPEC isolate in response to a single exposure to CORM-2 and after repeated exposure to CORM-2. The bacterial viability and minimal inhibitory concentration (MIC) were also examined after repeated exposure to CORM-2. Microarray analysis revealed that a wide range of processes were affected by CORM-2, including a general trend of down-regulation in energy metabolism and biosynthesis pathways and up-regulation of the SOS response and DNA repair. Several genes involved in virulence (ibpB), antibiotic resistance (marAB, mdtABC) and biofilm formation (bhsA, yfgF) were up-regulated, while some genes involved in virulence (kpsC, fepCEG, entABE), antibiotic resistance (evgA) and biofilm formation (artIP) were down-regulated. Repeated exposure to CORM-2 did not alter the gene expression patterns, the growth inhibitory response to CORM-2 or the MIC values for CORM-2, cefotaxime, ciprofloxacin and trimethoprim. This study identifies several enriched gene ontologies, modified pathways and single genes that are targeted by CORM-2 in a multidrug-resistant UPEC isolate. Repeated exposure to CORM-2 did not change the gene expression patterns or fold changes and the susceptibility to CORM-2 remained after repeated exposure.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Microbiology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-58779 (URN)10.1371/journal.pone.0178541 (DOI)000402880700036 ()28591134 (PubMedID)2-s2.0-85020463890 (Scopus ID)
Note

Funding Agencies:

Faculty of Medicine and Health at Örebro University  

Nyckelfonden at Örebro University Hospital 

Available from: 2017-07-26 Created: 2017-07-26 Last updated: 2017-11-29Bibliographically approved
Östling, H., Kruse, R., Helenius, G. & Lodefalk, M. (2017). Infants born small-for-gestational age have different placental expression of microRNAs. Paper presented at 10th International Meeting of Pediatric Endocrinology, Washington D.C., USA, September 14-17, 2017. Hormone Research in Paediatrics, 88(Suppl. 1), 100-101, Article ID P1-508.
Open this publication in new window or tab >>Infants born small-for-gestational age have different placental expression of microRNAs
2017 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, no Suppl. 1, p. 100-101, article id P1-508Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
S. Karger, 2017
National Category
Endocrinology and Diabetes Pediatrics
Identifiers
urn:nbn:se:oru:diva-62072 (URN)10.1159/000481424 (DOI)000412595401195 ()
Conference
10th International Meeting of Pediatric Endocrinology, Washington D.C., USA, September 14-17, 2017
Available from: 2017-10-30 Created: 2017-10-30 Last updated: 2017-12-14Bibliographically approved
Andersson, E., Bergemalm, D., Kruse, R., Neumann, G., D'Amato, M., Repsilber, D. & Halfvarson, J. (2017). Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles. PLoS ONE, 12(10), Article ID e0186142.
Open this publication in new window or tab >>Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 10, article id e0186142Article in journal (Refereed) Published
Abstract [en]

Objective: Genetic and immunological data indicate that inflammatory bowel disease (IBD) are characterized by specific inflammatory protein profiles. However, the serum proteome of IBD is still to be defined. We aimed to characterize the inflammatory serum protein profiles of Crohn's disease (CD) and ulcerative colitis (UC), using the novel proximity extension assay.

Methods: A panel of 91 inflammatory proteins were quantified in a discovery cohort of CD (n = 54), UC patients (n = 54), and healthy controls (HCs; n = 54). We performed univariate analyses by t-test, with false discovery rate correction. A sparse partial least-squares (sPLS) approach was used to identify additional discriminative proteins. The results were validated in a replication cohort.

Results: By univariate analysis, 17 proteins were identified with significantly different abundances in CD and HCs, and 12 when comparing UC and HCs. Additionally, 64 and 45 discriminant candidate proteins, respectively, were identified with the multivariate approach. Correspondingly, significant cross-validation error rates of 0.12 and 0.19 were observed in the discovery cohort. Only FGF-19 was identified from univariate comparisons of CD and UC, but 37 additional discriminant candidates were identified using the multivariate approach. The observed cross-validation error rate for CD vs. UC remained significant when restricting the analyses to patients in clinical remission. Using univariate comparisons, 16 of 17 CD-associated proteins and 8 of 12 UC-associated proteins were validated in the replication cohort. The area under the curve for CD and UC was 0.96 and 0.92, respectively, when the sPLS model from the discovery cohort was applied to the replication cohort.

Conclusions: By using the novel PEA method and a panel of inflammatory proteins, we identified proteins with significantly different quantities in CD patients and UC patients compared to HCs. Our data highlight the potential of the serum IBD proteome as a source for identification of future diagnostic biomarkers.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-61928 (URN)10.1371/journal.pone.0186142 (DOI)000412360300129 ()28982144 (PubMedID)2-s2.0-85030719034 (Scopus ID)
Funder
Swedish Foundation for Strategic Research , RB13-016Swedish Research Council, 521-2011-2764
Note

Funding Agency:

Örebro University Hospital Research Foundation  OLL-507001  OLL-526131

Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2019-04-05Bibliographically approved
Demirel, I., Rangel, I., Petersson, U., Persson, K. & Kruse, R. (2017). Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL)-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics. Frontiers in Microbiology, 8, Article ID 1058.
Open this publication in new window or tab >>Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL)-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics
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2017 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 8, article id 1058Article in journal (Refereed) Published
Abstract [en]

It is known that an ineffective antibiotic treatment can induce morphological shifts in uropathogenic Escherichia coli (UPEC) but the virulence properties during these shifts remain to be studied. The present study examines changes in global gene expression patterns and in virulence factor-associated genes in an extended spectrum beta-lactamase (ESBL)-producing UPEC (ESBL019) during the morphologic transitions induced by an ineffective antibiotic and in the presence of human primary bladder epithelial cells. Microarray results showed that the different morphological states of ESBL019 had significant transcriptional alterations of a large number of genes (Transition; 7%, Filamentation; 32%, and Reverted 19% of the entities on the array). All three morphological states of ESBL019 were associated with a decreased energy metabolism, altered iron acquisition systems and altered adhesion expression. In addition, genes associated with LPS synthesis and bacterial motility was also altered in all the morphological states. Furthermore, the transition state induced a significantly higher release of TNF-alpha from bladder epithelial cells compared to all other morphologies, while the reverted state was unable to induce INF-alpha release. Our findings show that the morphological shifts induced by ineffective antibiotics are associated with significant transcriptional virulence alterations in ESBL-producing UPEC, which may affect survival and persistence in the urinary tract.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2017
Keywords
filamentation, extended-spectrum beta-lactamase, uropathogenic Escherichia coli, ineffective antibiotics, morphological plasticity
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-58778 (URN)10.3389/fmicb.2017.01058 (DOI)000403139300001 ()28659883 (PubMedID)2-s2.0-85020493714 (Scopus ID)
Funder
Swedish Society of Medicine
Note

Funding Agencies:

Research Committee of Örebro County Council, Nyckelfonden

Faculty of Medicine and Health at Örebro University

Available from: 2017-07-26 Created: 2017-07-26 Last updated: 2018-02-05Bibliographically approved
Vumma, R., Bang, C. S., Kruse, R., Johansson, K. & Persson, K. (2016). Antibacterial effects of nitric oxide on uropathogenic Escherichia coli during bladder epithelial cell colonization-a comparison with nitrofurantoin. Journal of antibiotics (Tokyo. 1968), 69(3), 183-186
Open this publication in new window or tab >>Antibacterial effects of nitric oxide on uropathogenic Escherichia coli during bladder epithelial cell colonization-a comparison with nitrofurantoin
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2016 (English)In: Journal of antibiotics (Tokyo. 1968), ISSN 0021-8820, E-ISSN 1881-1469, Vol. 69, no 3, p. 183-186Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Japan Antibiotics Research Association, 2016
National Category
Immunology in the medical area Pharmacology and Toxicology
Research subject
Immunology
Identifiers
urn:nbn:se:oru:diva-49933 (URN)10.1038/ja.2015.112 (DOI)000373096800011 ()26531685 (PubMedID)
Note

Funding Agencies:

Swedish Council for Working Life and Social Research (FAS)

Nyckelfonden at Örebro University Hospital

Faculty of Medicine and Health at Örebro University

Available from: 2016-04-26 Created: 2016-04-26 Last updated: 2018-01-10Bibliographically approved
Sahlberg Bang, C., Kruse, R., Johansson, K. & Persson, K. (2016). Carbon monoxide releasing molecule-2 (CORM-2) inhibits growth of multidrug-resistant uropathogenic Escherichia coli in biofilm and following host cell colonization. BMC Microbiology, 16(1), Article ID 64.
Open this publication in new window or tab >>Carbon monoxide releasing molecule-2 (CORM-2) inhibits growth of multidrug-resistant uropathogenic Escherichia coli in biofilm and following host cell colonization
2016 (English)In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 16, no 1, article id 64Article in journal (Other academic) Published
Abstract [en]

Increased resistance to antimicrobial agents is a characteristic of many bacteria growing in biofilms on for example indwelling urinary catheters or in intracellular bacterial reservoirs. Biofilm-related infections caused by multidrug-resistant bacteria, such as extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, are a major challenge. The aim of this study was to investigate if a carbon monoxide-releasing molecule (CORM-2) has antibacterial effects against ESBL-producing uropathogenic E. coli (UPEC) in the biofilm mode of growth and following colonization of host bladder epithelial cells.

Results

The effect of CORM-2 was examined on bacteria grown within an established biofilm (biofilm formed for 24 h on plastic surface) by a live/dead viability staining assay. CORM-2 (500 μM) exposure for 24 h killed approximately 60 % of the ESBL-producing UPEC isolate. A non-ESBL-producing UPEC isolate and the E. coli K-12 strain TG1 were also sensitive to CORM-2 exposure when grown in biofilms. The antibacterial effect of CORM-2 on planktonic bacteria was reduced and delayed in the stationary growth phase compared to the exponential growth phase. In human bladder epithelial cell colonization experiments, CORM-2 exposure for 4 h significantly reduced the bacterial counts of an ESBL-producing UPEC isolate.

Conclusion

This study shows that CORM-2 has antibacterial properties against multidrug-resistant UPEC under biofilm-like conditions and following host cell colonization, which motivate further studies of its therapeutic potential.

Place, publisher, year, edition, pages
BioMed Central, 2016
National Category
Other Basic Medicine Microbiology
Identifiers
urn:nbn:se:oru:diva-49071 (URN)10.1186/s12866-016-0678-7 (DOI)000374282400001 ()27067266 (PubMedID)2-s2.0-84964033699 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare
Note

Funding Agencies:

Faculty of Medicine and Health at Orebro University 

 Nyckelfonden at Orebro University Hospital 

Available from: 2016-03-10 Created: 2016-03-10 Last updated: 2018-07-10Bibliographically approved
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