| 1. |
- Gustafsson, Anna, et al.
(författare)
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Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10, s. e7575-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The molecular biology of renal cell carcinoma (RCC) is complex and not fully understood. We have recently found that the expression of the receptor tyrosine kinase Axl in the RCC tumors independently correlates with survival of the patients. PRINCIPAL FINDINGS: Here, we have investigated the role of Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, in clear cell RCC (ccRCC) derived cells. The Axl protein was highly expressed in ccRCC cells deficient in functional von Hippel-Lindau (VHL) protein, a tumor suppressor gene often inactivated in ccRCC. VHL reconstituted cells expressed decreased levels of Axl protein, but not Axl mRNA, suggesting VHL to regulate Axl expression. Gas6-mediated activation of Axl in ccRCC cells resulted in Axl phosphorylation, receptor down-regulation, decreased cell-viability and migratory capacity. No effects of the Gas6/Axl system could be detected on invasion. Moreover, in ccRCC tumor tissues, Axl was phosphorylated and Gas6 gamma-carboxylated, suggesting these molecules to be active in vivo. SIGNIFICANCE: These results provide novel information regarding the complex function of the Gas6/Axl system in ccRCC.
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| 2. |
- Jankovskaja, Skaidre, et al.
(författare)
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Optimization of sample preparation for transporter protein quantification in tissues by LC–MS/MS
- 2019
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 164, s. 9-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reproducible quantification of drug transporter protein expression in tissues is important for predicting transporter mediated drug disposition. Many mass-spectrometry based transporter protein quantification methods result in high variability of the estimated transporter quantities. Therefore, we aimed to evaluate and optimize mass spectrometry-based quantification method for drug transporter proteins in tissues. Materials and methods: Plasma membrane (PM) proteins from mouse tissues were isolated by applying three extraction protocols: commercial plasma membrane extraction kit, tissue homogenization by Potter-Elvehjem homogenizer in combination with sucrose-cushion ultracentrifugation, and PM enrichment with Tween 40. Moreover, five different protein digestion protocols were applied on the same PM fraction. PM isolation and digestion protocols were evaluated by measuring the amount of transporter proteins by liquid chromatography-tandem mass spectrometry in selected reaction monitoring mode. Results: Mouse liver homogenization by Potter-Elvehjem homogenizer in combination with sucrose-cushion ultracentrifugation and PM enrichment with Tween 40 resulted in two times higher transporter protein quantity (Breast cancer resistance protein (Bcrp) 18.0 fmol/μg protein) in comparison with the PM samples isolated by extraction kit (Bcrp 9.8 fmol/μg protein). The evaluation of protein digestion protocols revealed that the most optimal protocol for PM protein digestion is with Lys-C and trypsin, in combination with trypsin enhancer and heat denaturation. Overall, quantities of Bcrp and Na+/K + ATPase proteins evaluated in mouse liver and kidney cortex by using our optimized PM isolation method, as well as, established digestion protocol were two to three times higher than previously reported and coefficient of variation (CV) for technical replicates was below 10%. Conclusion: We have established an improved transporter protein quantification methodology by optimizing PM isolation and protein digestion procedures. The optimized procedure resulted in a higher transporter protein yield and improved precision.
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| 3. |
- Ellervall, E, et al.
(författare)
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Antibiotic prophylaxis in oral healthcare - the agreement between Swedish recommendations and evidence.
- 2010
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Ingår i: British Dental Journal. - : Springer Science and Business Media LLC. - 1476-5373 .- 0007-0610. ; 208:3, s. 5-115
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Almost all (17/20) Swedish counties have pharmaceutical committees that establish recommendations for the use of antibiotic prophylaxis in oral healthcare.Objective To evaluate the evidence for the use of antibiotic prophylaxis in oral healthcare and the agreement between Swedish recommendations and evidence. MATERIAL AND METHODS: We conducted a systematic literature search in PubMed and the Cochrane Controlled Trials Register. The MeSH terms 'antibiotic prophylaxis' and 'dentistry' were used in the database search. Abstracts were reviewed according to specific inclusion and exclusion criteria. A total of 186 articles were read in full text by the four authors independently. Data extraction and interpretation of data was carried out using a pre-defined protocol. In the end, one case-control study was included for evaluation of evidence. RESULTS: The case-control study included patients with specific cardiac conditions. The study reported a 49% protective efficacy (odds ratio: 0.51) of antibiotic prophylaxis for first-time episodes of endocarditis within 30 days of procedure. This result was not statistically significant. The quality of the evidence was low. No studies were evaluated on patients with other medical conditions. The recommendations included several cardiac and other medical conditions for which there is a lack of evidence or no evidence to support the use of antibiotic prophylaxis.CONCLUSIONS: There is a lack of evidence to support the use of antibiotic prophylaxis. To avoid the risk of adverse events from antibiotics and the risk of developing resistant bacterial strains, the use of antibiotic prophylaxis should be minimised and recommendations in Sweden should be revised to be more evidence-based.
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| 4. |
- Lavant, Ewa H., et al.
(författare)
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HLA DR-DQ genotyping by capillary electrophoresis for risk assessment for celiac disease.
- 2013
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Ingår i: Clinical Applications of Capillary Electrophoresis. - Totowa, NJ : Humana Press. - 9781627030281 - 9781627030298 ; 919, s. 297-307
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The risk for celiac disease (CD) is clearly related to specific HLA DQA1 and DQB1 alleles, but HLA -typing is often considered too costly for frequent use.Here we present a method using sequence-specific primed PCR (PCR-SSP) for HLA-DR-DQ genotyping optimized for capillary electrophoresis on Applied Biosystems 3130xl Genetic Analyzer. Requiring a total of three PCR reactions and a single electrophoretic step, this method reduces the reagent expenses and technical time for directed HLA typing to distinguish risk alleles for CD, with a sufficient throughput for large-scale screening projects.
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| 5. |
- Liedberg, Birgitta, et al.
(författare)
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'Inadequate' dietary habits and mastication in elderly men
- 2007
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Ingår i: Gerodontology. - : Wiley. - 0734-0664 .- 1741-2358. ; 24:1, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- Objective: the aim of this study was to re-evaluate data about oral status, mastication and nutrition in elderly men in Malmö, Sweden, recorded in 1985-1987, to assess associations between inadequate dietary habits, oral conditions and masticatory function. Material and methods: Four hundred and eighty-one med, aged 67-68, participated in a comprehensive health examination, including tooth and denture status and masticatory tests. A separate study of dietary habits and nutritional status was made. Ninety-five men had inadequate dietary habits. The databases of dental/denture status, mastication, nutritional status and social network factors were re-evaluated for assessment of associations. Results: No significant differences between those with adequate or inadequate nutrition were found with regard to the number of teeth, occlusal contracts or removable dentures. Also self-assessed chewing did not show any differences. Conclusion: Inadequate dietary habits were independent of teeth and denture status. Some correlations to social network conditions could be identified. Overweight, obesity, low physical activity and high alcohol intake were more common among those with inadequate nutritional intake.
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| 6. |
- Svensson, Daniel, et al.
(författare)
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The host defense peptide LL-37 is detected in human parotid and submandibular/sublingual saliva and expressed in glandular neutrophils
- 2018
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Ingår i: European Journal of Oral Sciences. - : Blackwell Munksgaard. - 0909-8836 .- 1600-0722. ; 126:2, s. 93-100
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Tidskriftsartikel (refereegranskat)abstract
- The human host defense peptide, LL-37, is an important player in the first line of defense against invading microorganisms. LL-37 and its precursor, hCAP18, have been detected in unstimulated whole saliva but no reports showing hCAP18/LL-37 in isolated, parotid, and/or submandibular/sublingual saliva have been presented. Here, we measured the levels of hCAP18/LL-37 in human parotid and submandibular/sublingual saliva and investigated the expression of hCAP18/LL-37 in parotid and submandibular gland tissue. Parotid and submandibular/sublingual saliva was collected from healthy volunteers, and the levels of hCAP18/LL-37 in saliva were analyzed by dot blot, ELISA, and western blotting. Cellular expression of hCAP18/LL-37 in human parotid and submandibular glands was investigated by immunohistochemistry. Immunoreactivity for hCAP18/LL-37 was detected in both parotid and submandibular/sublingual saliva of all individuals. The concentration of hCAP18/LL-37 was similar in parotid and submandibular/sublingual saliva, and was determined by densitometric scanning of each dot and normalization to the total protein concentration of each sample, and by ELISA. Double immunohistochemistry revealed that intravascular neutrophils of both parotid and submandibular glands express hCAP18/LL-37. For the first time, we demonstrate hCAP18/LL-37 in isolated human parotid and submandibular/sublingual saliva and expression of hCAP18/LL-37 in glandular intravascular neutrophils, indicating that neutrophils of the major salivary glands contribute to the LL-37 content of whole saliva.
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| 7. |
- Correa, Yubexi, et al.
(författare)
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High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner
- 2023
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 645, s. 627-638
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Tidskriftsartikel (refereegranskat)abstract
- There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function. Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC). Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism.
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| 8. |
- Dahlstrom, M., et al.
(författare)
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Affinity states of biocides determine bioavailability and release rates in marine paints
- 2015
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Ingår i: Biofouling. - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 31:2, s. 201-210
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Tidskriftsartikel (refereegranskat)abstract
- A challenge for the next generation marine antifouling (AF) paints is to deliver minimum amounts of biocides to the environment. The candidate AF compound medetomidine is here shown to be released at very low concentrations, ie ng ml(-1) day(-1). Moreover, the release rate of medetomidine differs substantially depending on the formulation of the paint, while inhibition of barnacle settlement is independent of release to the ambient water, ie the paint with the lowest release rate was the most effective in impeding barnacle colonisation. This highlights the critical role of chemical interactions between biocide, paint carrier and the solid/aqueous interface for release rate and AF performance. The results are discussed in the light of differential affinity states of the biocide, predicting AF activity in terms of a high surface affinity and preserved bioavailability. This may offer a general framework for the design of low-release paint systems using biocides for protection against biofouling on marine surfaces.
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| 9. |
- Björklund, Sebastian, et al.
(författare)
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The effects of polar excipients transcutol and dexpanthenol on molecular mobility, permeability, and electrical impedance of the skin barrier
- 2016
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 479, s. 207-220
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Tidskriftsartikel (refereegranskat)abstract
- In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid-state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol.
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| 10. |
- Correa, Yubexi
(författare)
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Receptor-Independent Lipid Exchange of ApoA-I Amyloidogenic Variants in Reconstituted High-Density Lipoprotein
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- High-density lipoproteins (HDLs) are responsible for removing cholesterol from arterial walls, through a process known as reverse cholesterol transport. The main protein in HDL, apolipoprotein A-I (ApoAI), is essential to this process, and changes in its sequence significantly alter HDL structure and functionality. ApoA-I amyloidogenic variants, associated with a hereditary degenerative disease, are particularly effective at facilitating cholesterol removal, thus protecting carriers from cardiovascular disease. Thus, it is conceivable that reconstituted HDL (rHDL) formulations containing ApoA-I proteins with functional/structural features of amyloidogenic variants hold potential as a promising therapeutic approach. In this work, we explored the effect of protein cargo and lipid composition on the function of rHDL containing either the native ApoA-I or the amyloidogenic variants G26R and L174S. Moreover, we uncovered the structural and functional differences between rHDL particles to comprehend structural features that cause a rise in cholesterol efflux activity despite an apparent lower phospholipid (PL)affinity. Our findings indicate distinct trends in lipid exchange (removal versus deposition) capacities of various rHDL particles depending on protein cargo and PL unsaturation. Notably, the choice of lipid cargo influenced rHDL structure, resulting in smaller and more elliptical particles when POPC was used instead of DMPC. The study highlights the importance of the protein cargo, along with lipid composition, in shaping rHDL structure, contributing to our understanding of lipid-protein interactions and their behaviour.
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