| 1. |
- Angerfors, Annelie, et al.
(författare)
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Proteomic profiling identifies novel inflammation-related plasma proteins associated with ischemic stroke outcome
- 2023
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Ingår i: Journal of Neuroinflammation. - 1742-2094. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The inflammatory response to cerebral ischemia is complex; however, most clinical studies of stroke outcome focus on a few selected proteins. We, therefore, aimed to profile a broad range of inflammation-related proteins to: identify proteins associated with ischemic stroke outcome that are independent of established clinical predictors; identify proteins subsets for outcome prediction; and perform sex and etiological subtype stratified analyses.Methods Acute-phase plasma levels of 65 inflammation-related proteins were measured in 534 ischemic stroke cases. Logistic regression was used to estimate associations to unfavorable 3-month functional outcome (modified Rankin Scale score > 2) and LASSO regressions to identify proteins with independent effects.Results Twenty proteins were associated with outcome in univariable models after correction for multiple testing (FDR < 0.05), and for 5 the association was independent of clinical variables, including stroke severity (TNFSF14 [LIGHT], OSM, SIRT2, STAMBP, and 4E-BP1). LASSO identified 9 proteins that could best separate favorable and unfavorable outcome with a predicted diagnostic accuracy (AUC) of 0.81; three associated with favorable (CCL25, TRAIL [TNFSF10], and Flt3L) and 6 with unfavorable outcome (CSF-1, EN-RAGE [S100A12], HGF, IL-6, OSM, and TNFSF14). Finally, we identified sex- and etiologic subtype-specific associations with the best discriminative ability achieved for cardioembolic, followed by cryptogenic stroke.Conclusions We identified candidate blood-based protein biomarkers for post-stroke functional outcome involved in, e.g., NLRP3 inflammasome regulation and signaling pathways, such as TNF, JAK/STAT, MAPK, and NF-kappa B. These proteins warrant further study for stroke outcome prediction as well as investigations into the putative causal role for stroke outcome.
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| 2. |
- Asif, Muhammad H, et al.
(författare)
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Functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose
- 2010
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Ingår i: Biosensors & Bioelectronics. - : Elsevier BV. - 1873-4235 .- 0956-5663. ; 25:10, s. 2205-2211
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we report a functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose. To adjust the sensor for intracellular glucose measurements, we grew hexagonal ZnO nanorods on the tip of a silver-covered borosilicate glass capillary (0.7 mu m diameter) and coated them with the enzyme glucose oxidase. The enzyme-coated ZnO nanorods exhibited a glucose-dependent electrochemical potential difference versus an Ag/AgCl reference microelectrode. The potential difference was linear over the concentration range of interest (0.5-1000 mu M). The measured glucose concentration in human adipocytes or frog oocytes using our ZnO-nanorod sensor was consistent with values of glucose concentration reported in the literature; furthermore, the sensor was able to show that insulin increased the intracellular glucose concentration. This nanoelectrode device demonstrates a simple technique to measure intracellular glucose concentration. (C) 2010 Elsevier B.V. All rights reserved.
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| 3. |
- Brännmark, Cecilia, et al.
(författare)
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FIND Stroke Recovery Study (FIND): rationale and protocol for a longitudinal observational cohort study of trajectories of recovery and biomarkers poststroke
- 2023
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Ingår i: Bmj Open. - 2044-6055. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- ntroduction Comprehensive studies mapping domain-specific trajectories of recovery after stroke and biomarkers reflecting these processes are scarce. We, therefore, initiated an exploratory prospective observational study of stroke cases with repeated evaluation, the FIND Stroke Recovery Study. We aim to capture trajectories of recovery from different impairments, including cognition, in combination with broad profiling of blood and imaging biomarkers of the recovery. Methods and analysis We recruit individuals with first-ever stroke at the stroke unit at the Sahlgrenska University Hospital, Sweden, to FIND. The inclusion started early 2018 and we aim to enrol minimum 500 patients. Neurological and cognitive impairments across multiple domains are assessed using validated clinical assessment methods, advanced neuroimaging is performed and blood samples for biomarker measuring (protein, RNA and DNA) at inclusion and follow-up visits at 3 months, 6 months, 1 year, 2 years and 5 years poststroke. At baseline and at each follow-up visit, we also register clinical variables known to influence outcomes such as prestroke functioning, stroke severity, acute interventions, rehabilitation, other treatments, socioeconomic status, infections (including COVID-19) and other comorbidities. Recurrent stroke and other major vascular events are identified continuously in national registers. Ethics and dissemination FIND composes a unique stroke cohort with detailed phenotyping, repetitive assessments of outcomes across multiple neurological and cognitive domains and patient-reported outcomes as well as blood and imaging biomarker profiling. Ethical approval for the FIND study has been obtained from the Regional Ethics Review Board in Gothenburg and the Swedish Ethics Review Board. The results of this exploratory study will provide novel data on the time course of recovery and biomarkers after stroke. The description of this protocol will inform the stroke research community of our ongoing study and facilitate comparisons with other data sets.
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| 4. |
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| 5. |
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| 6. |
- Fulati, Alimujiang, 1981-, et al.
(författare)
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An intracellular glucose biosensor based on nanoflake ZnO
- 2010
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 150:2, s. 673-680
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this study, an improved potentiometric intracellular glucose biosensor was fabricated with immobilization of glucose oxidase on a ZnO nanoporous material. The ZnO nanoporous material with a wall thickness around 200 nm was grown on the tip of a borosilicate glass capillary and used as a selective intracellular glucose sensor for the measurement of glucose concentrations in human adipocytes and frog oocytes. The results showed a fast response within 4 s and a linear glucosedependent electrochemical response over a wide range of glucose concentration (500 nM-10 mM). The measurements of intracellular glucose concentrations with our biosensor were consistent with the values of intracellular glucose concentrations reported in the literature. The sensor also demonstrated its capability by detecting an increase in the intracellular glucose concentration induced by insulin. We found that the ZnO nanoporous material provides sensitivity as high as 1.8 times higher than that obtained using ZnO nanorods under the same conditions. Moreover, the fabrication method in our experiment is simple and the excellent performance of the developed nanosensor in sensitivity, stability, selectivity, reproducibility and anti-interference was achieved. All these advantageous features of this intracellular glucose biosensor based on functionalised ZnO nanoporous material compared to ZnO nanorods demonstrate a promising way of enhancing glucose biosensor performance to measure reliable intracellular glucose concentrations within single living cells.
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| 7. |
- Paul, A., et al.
(författare)
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Quantitative Mapping of Triacylglycerol Chain Length and Saturation Using Broadband CARS Microscopy
- 2019
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495. ; 116:12, s. 2346-2355
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Tidskriftsartikel (refereegranskat)abstract
- Lipid droplets (LDs), present in many cell types, are highly dynamic organelles that store neutral lipids, primarily triacylglycerols (TAGs). With the discovery of new LD functions (e.g., in immune response, protein clearage, and occurrence with disease), new methods to study LD chemical composition in situ are necessary. We present an approach for in situ, quantitative TAG analysis using label-free, coherent Raman microscopy that allows deciphering LD TAG composition in different biochemically complex samples with submicrometer spatial resolution. Employing a set of standard TAGs, we generate a spectral training matrix capturing the variation caused in Raman-like spectra by TAG backbone, chain length, and number of double bonds per chain, as well as the presence of proteins or other diluting molecules. Comparing our fitting approach to gas chromatography measurements for mixtures of standard TAGs and food oils, we find the root mean-square error for the prediction of TAG chemistry to be 0.69 CH2 and 0.15 #C=C. When progressing to more complex samples such as oil emulsions and LDs in various eukaryotic cells, we find good agreement with bulk gas chromatography measurements. For differentiated adipocytes, we find a significant increase in the number of double bonds in small LDs (below 2 mu m in diameter) compared to large LDs (above 2 mu m in diameter). Coupled with a relatively limited sample preparation requirement, this approach should enable rapid and accurate TAG LD analysis for a variety of cell biology and technological applications.
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| 8. |
- Rajan, M. R., et al.
(författare)
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Inhibition of FOXO1 transcription factor in primary human adipocytes mimics the insulin-resistant state of type 2 diabetes
- 2018
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Ingår i: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 475:10, s. 1807-1820
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is characterized by insulin resistance in the expanding adipose tissue of obesity. The insulin resistance manifests in human adipocytes as system-wide impairment of insulin signalling. An exception is the regulation of transcription factor FOXO1 (forkhead box protein O1), which is phosphorylated downstream of mTORC2 (mammalian/mechanistic target of rapamycin in complex with raptor) and is therefore not exhibiting impaired response to insulin. However, the abundance, and activity, of FOXO1 is reduced by half in adipocytes from patients with diabetes. To elucidate the effect of reduced FOXO1 activity, we here transduced human adipocytes with a dominant-negative construct of FOXO1 (DN-FOXO1). Inhibition of FOXO1 reduced the abundance of insulin receptor, glucose transporter-4, ribosomal protein S6, mTOR and raptor. Functionally, inhibition of FOXO1 induced an insulin-resistant state network-wide, a state that qualitatively and quantitatively mimicked adipocytes from patients with type 2 diabetes. In contrast, and in accordance with these effects of DN-FOXO1, overexpression of wild-type FOXO1 appeared to augment insulin signalling. We combined experimental data with mathematical modelling to show that the impaired insulin signalling in FOXO1-inhibited cells to a large extent can be explained by reduced mTORC1 activity - a mechanism that defines much of the diabetic state in human adipocytes. Our findings demonstrate that FOXO1 is critical for maintaining normal insulin signalling of human adipocytes.
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| 9. |
- Stanne, Tara M, 1979, et al.
(författare)
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Association of Plasma Brain-Derived Tau With Functional Outcome After Ischemic Stroke.
- 2024
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Ingår i: Neurology. - 1526-632X. ; 102:4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether circulating acute-phase brain-derived tau (BD-tau) is associated with functional outcome after ischemic stroke.Plasma tau was measured by a novel assay that selectively quantifies BD-tau in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which includes adult cases with ischemic stroke and controls younger than 70 years, and in an independent cohort of adult cases of all ages (SAHLSIS2). Associations with unfavorable 3-month functional outcome (modified Rankin scale score >2) were analyzed by logistic regression. Various stratified and sensitivity analyses were performed, for example, by age, stroke severity, recanalization therapy, and etiologic subtype.This study included 454 and 364 cases from the SAHLSIS and SAHLSIS2, with a median age of 58 and 68 years, respectively. Higher acute BD-tau concentrations were significantly associated with increased odds of unfavorable outcome after adjustment for age, sex, day of blood draw, and stroke severity (NIH stroke scale score) in both cohorts (OR per doubling of BD-tau: 2.9 [95% CI 2.2-3.7], P = 1 × 10-15 and 1.8 [1.5-2.2], P = 7 × 10-9, respectively). The association was consistent in the different stratified and sensitivity analyses.BD-tau is a promising blood-based biomarker of ischemic stroke outcomes, and future studies in larger cohorts are warranted.
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| 10. |
- Stanne, Tara M, 1979, et al.
(författare)
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Longitudinal Study Reveals Long-Term Proinflammatory Proteomic Signature After Ischemic Stroke Across Subtypes
- 2022
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 53:9, s. 2847-2858
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammation contributes both to the pathogenesis of stroke and the response to brain injury. We aimed to identify proteins reflecting the acute-phase response and proteins more likely to reflect proinflammatory processes present before stroke by broadly profiling inflammation-related plasma proteins in a longitudinal ischemic stroke study. Methods: Participants were from a Swedish ischemic stroke cohort (SAHLSIS [Sahlgrenska Academy Study on Ischemic Stroke], n=600 cases and n=600 controls). Plasma levels of 65 proteins including chemokines, interleukins, surface molecules, and immune receptors were measured once in controls and at 3x in cases: during the acute phase, after 3 months, and for a subgroup (n=223) at 7-year follow-up. Associations between proteins and ischemic stroke or subtype were investigated in multivariable binary regression models corrected for age, sex, vascular risk factors, and multiple testing. Results: In the acute phase, 48 proteins were significantly and independently associated with ischemic stroke (false discovery rate adjusted P<0.05). At 3-month follow-up, 51 proteins and at 7-year follow-up 50 proteins were associated with ischemic stroke. The majority of proteins were upregulated in cases compared with controls (n=34 at all time points) and the most upregulated were CXCL5 (CXC chemokine ligand 5) and OSM (oncostatin M). Generally, large artery and cardioembolic stroke had the highest protein levels. However, several interesting subtype-specific differences were also detected at each time point. Conclusions: We found inflammation-related proteins that were differentially regulated in ischemic stroke cases compared with controls only in the acute phase and others that remained elevated also at later time points. This latter group of proteins could reflect underlying pathophysiological processes of relevance. Future studies both in terms of disease risk and prognostication are warranted.
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