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- Nowinski, Daniel, 1972-
(författare)
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Regulation of Fibroblast Activity by Keratinocytes
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the healing of cutaneous wounds, paracrine communication between keratinocytes and fibroblasts regulates cell differentiation, proliferation and synthesis of extracellular matrix. Deficient epidermal coverage, as seen in burn-wounds, frequently results in hypertrophic scars. Previous studies suggest that keratinocytes downregulate the production of collagen and profibrotic factors in fibroblasts. We hypothesized that keratinocytes downregulate the expression of the profibrotic factor connective tissue growth factor (CTGF) in fibroblasts, and regulate fibroblast expression of genes important to wound healing. In keratinocyte-fibroblast cocultures, keratinocytes downregulated CTGF mRNA and protein in fibroblasts, through the secretion of interleukin-1 (IL-1) α. Using Affymetrix DNA microarrays, it was demonstrated that factors from keratinocytes regulate the expression of 69 genes important to wound healing. The regulation of 16 of these genes was confirmed by Northern blotting, and IL-1α from keratinocytes regulated all the 16 genes examined. IL-1-mediated CTGF gene regulation was further investigated. Both IL-1 isoforms, α and β, suppressed CTGF expression through an inhibition of CTGF promoter activity. Interestingly, transforming growth factor-β-stimulated Smad phosphorylation was not affected by IL-1. Finally, we hypothesized that CTGF is downregulated in burn wound by split-thickness skin grafting and that the expression of CTGF is suppressed during reepithelialization. The expression of CTGF protein was decreased in successfully skin-grafted wound areas, and increased in open, granulating burn wounds. Moreover, CTGF protein expression was absent beneath the migrating edge of reepithelialization ex vivo. In conclusion, we demonstrate that, in in vitro models, keratinocyte-derived IL-1α regulates the expression of CTGF and other genes with importance to wound healing. Furthermore, it is shown that CTGF expression is suppressed by epidermal wound coverage i burn wounds. These findings may have implications for the understanding of keratinocyte-fibroblast interplay during wound healing and in hypertrophic scar pathogenesis.
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| 3. |
- Scanlan, Leona D, et al.
(författare)
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Gene transcription, metabolite and lipid profiling in eco-indicator daphnia magna indicate diverse mechanisms of toxicity by legacy and emerging flame-retardants.
- 2015
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:12
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Tidskriftsartikel (refereegranskat)abstract
- The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, (1)H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/10(6) LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia.
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| 6. |
- De Piano, Mario, et al.
(författare)
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Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases
- 2020
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Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 39:18, s. 3666-3679
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer.
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| 7. |
- George, Leena, et al.
(författare)
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Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma
- 2020
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:2, s. 370-380
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whether the clinical or pathophysiologic significance of the "treatable trait" high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma.Methods: Subjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U-BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U-BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil > 200 cells/mu L as a cut-off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values).Results: There were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U-BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts.Conclusion: Despite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.
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| 9. |
- Mohd Shah, Syaiful Redzwan, 1984-, et al.
(författare)
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Microwave-Sensor-Based Clinical Measurements for Monitoring Post-Craniotomy Bone Development in Pediatric Craniosynostosis Patients
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Tidskriftsartikel (refereegranskat)abstract
- The bone density analysis system is a new method to analyze the amount of bone healed in cranial vault defects. Craniotomy creates such defects to treat pediatric patients with craniosynostosis. This method uses the variations in the resonance of a microwave sensor attached to the area under test in the patient. Data were collected from infants treated for craniosynostosis through craniotomy surgery in clinical trials. The data, which consist of resonance parameters (frequency, amplitude, and Q-factor) is collected using a microwave-based biomedical sensor. This sensor could detect changes in the resonance as changes in the permittivity of the various tissues at the ISM band. By observing differences between a reference and target defect points, bone healing over time could be accessed. In this paper, we analyze the validity of a proposed Computational Simulation Technology (CST) based numerical model for the sensor and extend the clinical data analysis from previous works with our bone density analysis system. The validity of the model is analyzed by comparing its outcomes to available measurements from numerical simulations, phantoms mimicking living tissues and clinical trial. In the data analysis, a hypothesis is formulated and tested regarding the healing over time. By deriving a set of parameters for each collected dataset in the clinical trials, a distinct pattern was found which shows visible changes such as edema and tissue thickening over the course of the healing process with this technique. Moreover, we manage to distinguish significant differences between the reference and defect points after the craniosynostosis surgery.
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| 10. |
- Perez, Mauricio D., et al.
(författare)
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Head-compliant microstrip split ring resonator for non-invasive healing monitoring after craniosynostosis-based surgery
- 2020
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Ingår i: HEALTHCARE TECHNOLOGY LETTERS. - : INST ENGINEERING TECHNOLOGY-IET. - 2053-3713. ; 7:1, s. 29-34
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Tidskriftsartikel (refereegranskat)abstract
- A soft and highly directive, proximity-coupled split-ring resonator fabricated with a liquid alloy, copper and polydimethylsiloxane (PDMS) is presented. The same was designed for sensing osteogenesis of calvarial bone. As dielectric properties of bone grafts in ossifying calvarial defects should change during the osteogenesis process, devices like this could monitor the gradual transformation of the defect into bone by differentiating changes in the dielectric properties as shifts in the resonance frequency. Computational Software Technology (CST) Microwave Studio (R)-based simulation results on computational head models were in good agreement with laboratory results on head phantom models, which also included the comparison with an in-vivo measurement on the human head. A discussion based on an inductive reasoning regarding dynamics' considerations is provided as well. Since the skin elasticity of newborn children is high, stretching and crumpling could be significant. In addition, due to typical head curvatures in newborn children, bending should not be a significant issue, and can provide higher energy focus in the defect area and improve conformability. The present concept could support the development of soft, cheap and portable follow-up monitoring systems to use in outpatient hospital and home care settings for post-operative monitoring of bone healing after reconstructive surgical procedures.
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| 11. |
- Perez, Mauricio D., et al.
(författare)
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New Approach for Clinical Data Analysis of Microwave Sensor Based Bone Healing Monitoring System in Craniosynostosis Treated Pediatric Patients
- 2018
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Ingår i: 2018 IEEE Conference On Antenna Measurements & Applications (CAMA). - : IEEE. - 9781538657959
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Konferensbidrag (refereegranskat)abstract
- In the BDAS project one of the goals is to provide a solution to the monitoring bone healing issue complementing current techniques. Data have been collected in clinical trials from infants treated for Craniosynostosis by a craniotomy surgery. The data are collected with a biomedical sensor based in microwave technology. This sensor could be able to sense changes in the composition of the different tissues in the upper-hemisphere of the head by noticing a difference in the propagation of the microwaves, as the bone injury from the craniotomy heals over time. In this thesis, we analyse the clinical data in BDAS project incorporating new approaches with respect to previous analysis methods. These new approaches could give new insight into the proposed solution, but more analysis need to be done.
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| 13. |
- Redzwan, Syaiful, et al.
(författare)
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Initial in-vitro trial for intra-cranial pressure monitoring using subdermal proximity-coupled split-ring resonator
- 2018
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Ingår i: IMBioc 2018 - 2018 IEEE/MTT-S International Microwave Biomedical Conference. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538659182 ; , s. 73-75
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Konferensbidrag (refereegranskat)abstract
- Intra cranial pressure (ICP) monitoring is used in treating severe traumatic brain injury (TBI) patients. All current clinical available measurement methods are invasive presenting considerable social costs. This paper presents a preliminary investigation of the feasibility of ICP monitoring using an innovative microwave-based non-invasive approach. A phantom mimicking the dielectric characteristics of human tissues of the upper part of the head at low microwave frequencies is employed together to a proof-of-concept prototype based on the proposed approach consisting in a readout system and a sub-dermally implanted passive device, both based in split ring resonator techniques. This study shows the potential of our approach to detect two opposite pressure variation stages inside the skull. The employed phantom model needs to be improved to support finer variations in the pressure and better phantom parts, principally for the skull mimic and the loss tangent of all mimics.
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| 14. |
- Tarnow, Peter, 1963, et al.
(författare)
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Incidence of Non-Syndromic and Syndromic Craniosynostosis in Sweden
- 2022
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Ingår i: Journal of Craniofacial Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1049-2275. ; 33:5, s. 1517-1520
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Tidskriftsartikel (refereegranskat)abstract
- Premature craniosynostosis is a rare condition, with a wide range of incidence estimations in the literature. The aim of this study was to establish the current incidence among the Swedish population. Since the surgical care for these children is centralized to the 2 centers of Sahlgrenska University Hospital and Uppsala University Hospital, the 2 craniofacial hospital registries were examined for surgically treated children, all having a computed tomography verified diagnosis. Results show an incidence of 7.7 cases per 10,000 live births, including 0.60/10,000 syndromic craniosynostosis. Due to information programs among health care staff and a system for early diagnosis through rapid communication, these results seem to mirror the true incidence of craniosynostosis in the Swedish population. The updated incidence data will facilitate healthcare planning and make future studies of possible changes in craniosynostosis incidence more accurate.
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| 16. |
- Velander, Jacob, et al.
(författare)
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A Four-Layer Phantom for Testing In-Vitro Microwave-Based Sensing Approach in Intra-Cranial Pressure Monitoring
- 2018
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Ingår i: Proceedings Of The 2018 IEEE/MTT-S International Microwave Biomedical Conference (IMBioC). - : IEEE. - 9781538659182 ; , s. 49-51
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Konferensbidrag (refereegranskat)abstract
- Multi-layer phantoms in proofs of concept, designs and validations of both microwave-based biomedical sensing and imaging system are becoming popular means to facilitate in-vitro experiments. In addition, they can contribute significantly to reduce animal use in scientific experimentation. In this paper, we design and fabricate a four-layer phantom composed of skin, skull, cerebrospinal fluid and brain mimic tissues to work between 2 and 3 GHz. In addition, the phantom incorporates a mechanism to produce pressure variation between the cerebrospinal fluid and the brain mimic tissues. This phantom is used in an in-vitro experiment to test and validate a new approach which could sense intra-cranial pressure variations through a microwave-based reflection method. The similarity of the phantom's tissues with human tissues from the viewpoint of the microwave response is analyzed in comparison with data from Italian Institute of Applied Physics in Florence. We found good agreement for the dielectric constant (Rel. Err. < 13 % for 68% of significance) in skin, cerebrospinal fluid and brain mimic tissues. For the skin, we got also good agreement for the loss tangent (Rel. Err. < 11 % for 68% of significance). The skull mimic phantom was stiff enough, but even presenting considerable errors, it was still good enough for the experiment. In addition, the capability of the phantom to operate at different pressures is discussed.
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