| 1. |
- Cong, Goh Zheng, et al.
(författare)
-
Targeted pancreatic beta cell imaging for early diagnosis
- 2020
-
Ingår i: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 99:7
-
Forskningsöversikt (refereegranskat)abstract
- Pancreatic beta cells are important in blood glucose level regulation. As type 1 and 2 diabetes are getting prevalent worldwide, we need to explore new methods for early detection of beta cell-related afflictions. Using bioimaging techniques to measure beta cell mass is crucial because a decrease in beta cell density is seen in diseases such as diabetes and thus can be a new way of diagnosis for such diseases. We also need to appraise beta cell purity in transplanted islets for type 1 diabetes patients. Sufficient amount of functional beta cells must also be determined before being transplanted to the patients. In this review, indirect imaging of beta cells will be discussed. This includes membrane protein on pancreatic beta cells whereby specific probes are designed for different imaging modalities mainly magnetic resonance imaging, positron emission tomography and fluorescence imaging. Direct imaging of insulin is also explored though probes synthesized for such function are relatively fewer. The path for successful pancreatic beta cell imaging is fraught with challenges like non-specific binding, lack of beta cell-restricted targets, the requirement of probes to cross multiple lipid layers to bind to intracellular insulin. Hence, there is an urgent need to develop new imaging techniques and innovative probing constructs in the entire imaging chain of bioengineering to provide early detection of beta cell-related pathology.
|
|
| 2. |
- Kurtyka, Magdalena, et al.
(författare)
-
The solute carrier SLC7A1 may act as a protein transporter at the blood-brain barrier
- 2024
-
Ingår i: European Journal of Cell Biology. - : Elsevier. - 0171-9335 .- 1618-1298. ; 103:2
-
Tidskriftsartikel (refereegranskat)abstract
- Despite extensive research, targeted delivery of substances to the brain still poses a great challenge due to the selectivity of the blood -brain barrier (BBB). Most molecules require either carrier- or receptor -mediated transport systems to reach the central nervous system (CNS). These transport systems form attractive routes for the delivery of therapeutics into the CNS, yet the number of known brain endothelium -enriched receptors allowing the transport of large molecules into the brain is scarce. Therefore, to identify novel BBB targets, we combined transcriptomic analysis of human and murine brain endothelium and performed a complex screening of BBBenriched genes according to established selection criteria. As a result, we propose the high -affinity cationic amino acid transporter 1 (SLC7A1) as a novel candidate for transport of large molecules across the BBB. Using RNA sequencing and in situ hybridization assays, we demonstrated elevated SLC7A1 gene expression in both human and mouse brain endothelium. Moreover, we confirmed SLC7A1 protein expression in brain vasculature of both young and aged mice. To assess the potential of SLC7A1 as a transporter for larger proteins, we performed internalization and transcytosis studies using a radiolabelled or fluorophore-labelled anti-SLC7A1 antibody. Our results showed that SLC7A1 internalised a SLC7A1-specific antibody in human colorectal carcinoma (HCT116) cells. Moreover, transcytosis studies in both immortalised human brain endothelial (hCMEC/D3) cells and primary mouse brain endothelial cells clearly demonstrated that SLC7A1 effectively transported the SLC7A1specific antibody from luminal to abluminal side. Therefore, here in this study, we present for the first time the SLC7A1 as a novel candidate for transport of larger molecules across the BBB.
|
|
| 3. |
- Maaninka, Katariina, et al.
(författare)
-
OxLDL sensitizes platelets for increased formation of extracellular vesicles capable of finetuning macrophage gene expression
- 2023
-
Ingår i: European Journal of Cell Biology. - : Elsevier. - 0171-9335 .- 1618-1298. ; 102:2
-
Tidskriftsartikel (refereegranskat)abstract
- Platelet extracellular vesicles (PEVs) generated upon platelet activation may play a role in inflammatory pathologies such as atherosclerosis. Oxidized low-density lipoprotein (oxLDL), a well-known contributor to atherogenesis, activates platelets and presensitizes them for activation by other agonists. We studied the effect of oxLDL on the secretion, composition, and inflammatory functions of PEVs using contemporary EV analytics. Platelets were activated by co-stimulation with thrombin (T) and collagen (C) ± oxLDL and characterized by high-resolution flow cytometry, nanoparticle tracking analysis, proximity extension assay, western blot, and electron microscopy. The effect of PEVs on macrophage differentiation and functionality was examined by analyzing macrophage surface markers, cytokine secretion, and transcriptome. OxLDL upregulated TC-induced formation of CD61+, P-selectin+ and phosphatidylserine+ PEVs. Blocking the scavenger receptor CD36 significantly suppressed the oxLDL+TC-induced PEV formation, and HDL caused a slight but detectable suppression. The inflammatory protein cargo differed between the PEVs from stimulated and unstimulated platelets. Both oxLDL+TC- and TC-induced PEVs enhanced macrophage HLA-DR and CD86 expression and decreased CD11c expression as well as secretion of several cytokines. Pathways related to cell cycle and regulation of gene expression, and immune system signaling were overrepresented in the differentially expressed genes between TC PEV -treated vs. control macrophages and oxLDL+TC PEV -treated vs. control macrophages, respectively. In conclusion, we speculate that oxLDL and activated platelets contribute to proatherogenic processes by increasing the number of PEVs that provide an adhesive and procoagulant surface, contain inflammatory mediators, and subtly finetune the macrophage gene expression.
|
|
| 4. |
|
|
| 5. |
- Muslimovic, Aida, et al.
(författare)
-
Novel clearance of muscle proteins by muscle cells
- 2020
-
Ingår i: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 99:8
-
Tidskriftsartikel (refereegranskat)abstract
- Blood levels of cardiac troponins (cTn) and myoglobin are analysed when myocardial infarction (MI) is suspected. Here we describe a novel clearance mechanism for muscle proteins by muscle cells. The complete plasma clearance profile of cTn and myoglobin was followed in rats after intravenous or intermuscular injections and analysed by PET and fluorescence microscopy of muscle biopsies and muscle cells. Compared with intravenous injections, only 5 % of cTnT, 0.6 % of cTnI and 8 % of myoglobin were recovered in the circulation following intramuscular injection. In contrast, 47 % of the renal filtration marker FITC-sinistrin and 81 % of cTn fragments from MI-patients were recovered after intramuscular injection. In addition, PET and biopsy analysis revealed that cTn was taken up by the quadriceps muscle and both cTn and myoglobin were endocytosed by cultured muscle cells. This local clearance mechanism could possibly be the dominant clearance mechanism for cTn, myoglobin and other muscle damage biomarkers released by muscle cells.
|
|
| 6. |
- Zambarda, Chiara, et al.
(författare)
-
Epithelial cell cluster size affects force distribution in response to EGF-induced collective contractility
- 2022
-
Ingår i: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 101:4, s. 151274-
-
Tidskriftsartikel (refereegranskat)abstract
- Several factors present in the extracellular environment regulate epithelial cell adhesion and dynamics. Among them, growth factors such as EGF, upon binding to their receptors at the cell surface, get internalized and directly activate the acto-myosin machinery. In this study we present the effects of EGF on the contractility of epithelial cancer cell colonies in confined geometry of different sizes. We show that the extent to which EGF triggers contractility scales with the cluster size and thus the number of cells. Moreover, the collective contractility results in a radial distribution of traction forces, which are dependent on integrin beta 1 peripheral adhesions and trans-mitted to neighboring cells through adherens junctions. Taken together, EGF-induced contractility acts on the mechanical crosstalk and linkage between the cell-cell and cell-matrix compartments, regulating collective responses.
|
|
