Biology subjects

Rolfsson, O.

Publications and source records attributed to Rolfsson, O..

5 recordsLinked to original sources

bioRxiv2024

Weak Modulation of Human Glycolysis Isomerases by Metabolites: A Screening Study

Modulation of enzyme activity by metabolites represents the most efficient and rapid way of controlling metabolism. Investigating enzyme-metabolite interactions can deepen our understanding of metabolic control and aid in identifying enzyme modulators with potential therapeutic applications. These interactions vary in strength, with dissociation constants (Kd) ranging from strong (nM) to weak ({micro}M-mM). However, weak interactions are often overlooked due to the challenges in studying them. Despite this, weak modulators can reveal novel binding modes and serve as starting points for compound optimization. In this study, we aim to identify metabolites that weakly modulate the activity of human glucose-6-phosphate isomerase (GPI) and triosephosphate isomerase (TPI), which are potential therapeutic targets in tumor glycolysis. Through a combination of activity and binding assays, the screening revealed multiple weak inhibitors for the two targets, causing partial attenuation of their activity, with Kd and Ki in the low mM range. X-ray crystallography revealed six orthosteric ligands binding to the active sites - four inhibitors of GPI and two of TPI. Our findings underscore the role of weak interactions in enzyme regulation and may provide structural insights that could guide the design of inhibitors targeting human GPI and TPI in cancer intervention. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=45 SRC="FIGDIR/small/610356v2_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@574540org.highwire.dtl.DTLVardef@1837c4forg.highwire.dtl.DTLVardef@15661c8org.highwire.dtl.DTLVardef@2db0ed_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2021

Virucidal activity of a proprietary blend of plant-based oils (Viruxal) against SARS-CoV-2 and influenza viruses - an in vitro study

BackgroundThe emergence of a novel coronavirus known as SARS-CoV-2 resulting in a global pandemic COVID-19 has led to a dramatic loss of life worldwide and presented an unprecedented challenge to public health. Viruxal is a medical device in a form of a nasal and oral spay containing a a proprietary blend of plant-based oils which acts against enveloped viruses. The aim of this study was to evaluate the virus deactivation activity of Viruxal against SARS-CoV-2 and Influenza A(H1N1) viruses. MethodsAn assay to detect virucidal activity was performed with four concentrations of Viruxal on two virus suspensions. Assessments were made based on log reduction values measured from the assay. ResultsViruxal exhibited virucidal activity by reducing virus titer more than 90% for the enveloped viruses SARS-CoV-2 and influenza A(H1N1) after 30 minutes contact. ConclusionsViruxal was validated for its potential usefulness as a medical device for treatment and prevention of enveloped respiratory viruses.

microbiology↗

bioRxiv2021

Lipid mediator profile of burn wound healing: Acellular cod fish skin grafts promote the formation of EPA and DHA derived lipid mediators during the first seven days

The use of acellular fish skin grafts (FSG) for the treatment of burn wounds is becoming more common due to its beneficial wound healing properties. In our previous study we demonstarted that FSG is a scaffold biomaterial that is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) conjugated to phosphatidylcholines. Here we investigated whether EPA and DHA derived lipid mediators are influenced during the healing of burn wounds treated with FSG. Deep partial and full thickness burn wounds (DPT and FT respectively) were created on Yorkshire pigs (n=4). DPT were treated with either FSG or fetal bovine dermis while FT were treated either with FSG or cadaver skin initially and followed by a split thickness skin graft. Punch biopsies were collected on days 7, 14, 21, 28 and 60 and analysed in respect of changes to approximately 45 derivatives of EPA, DHA, arachidonic acid (AA), and linoleic acid (LA) employing UPLC-MS/MS methodology. Several EPA and DHA derivatives, including 18-HEPE and 17-HDHA, were significantly higher on day 7 in the DPT when treated with FSG. A similar but non-significant trend was observed for the FT. In addition, prostaglandin F2 and its 15-keto derivative (AA pathway) as well as 13-HODE and 13-HOTrE (LA pathway) were significantly lower in the FSG treated FT. The results suggest that the use of FSG in burn wound treatment can alter the formation of EPA and DHA mono hydroxylated lipid mediators in comparison to other grafts of mammalian origin. The differences observed during the first seven days after treatment indicates that FSG affects the early stages of wound healing. HighlightsO_LIThis is the first study to investigate whether omega-3 rich biomaterial such as fish skin graft can affect the lipidome of burn wound healing C_LIO_LIThe study monitors the formation of lipid mediators during 60 days of burn wound healing C_LIO_LIThis is the first study to show an increase in the formation of mono-hydroxylated derivatives of EPA and DHA after seven days of treatment with fish skin graft C_LIO_LIThe study showed significantly decreased formation of lipid mediators involved in pain modulation in wounds treated with fish skin graft C_LI

biochemistry↗

bioRxiv2019

The temperature dependence of platelet metabolism

Temperature plays a fundamental role in biology, influencing cellular function, affecting chemical reaction rates, molecular structures, and interactions. While the temperature dependence of many biochemical reactions is well defined in vitro, the effect of temperature on metabolic function at the network level is not well understood but remains an important challenge in optimizing the storage of cells and tissues at lower temperatures. Here, we have used time-course metabolomics data and systems biology approaches to characterize the effects of storage temperature on human platelets (PLTs) in platelet additive solution. We observed that changes to the metabolome with storage time do not simply scale with temperature but instead display complex temperature dependence, with only a small subset of metabolites following an Arrhenius-type. Investigation of PLT energy metabolism through integration with computational modeling revealed that oxidative metabolism is more sensitive to temperature changes than is glycolysis. The increased contribution of glycolysis to ATP turnover at lower temperature indicates a stronger glycolytic phenotype with decreasing storage temperature. More broadly, these results demonstrate that the temperature dependence of the PLT metabolic network is not uniform, suggesting that efforts to improve the health of stored PLTs could be targeted at specific pathways.\n\nStatement of SignificanceThe temperature dependence of cellular metabolism is difficult to study due to regulatory events that are activated upon deviation from the optimal temperature range. Platelets are blood components used in transfusion medicine but also serve as a model cell to study human energy metabolism in the absence of genetic regulation. We investigated changes in platelet metabolism at temperatures spanning from 4 {degrees}C-37 {degrees}C using a quantitative metabolic systems biology approach as opposed to assessing individual reactions. We found that energy producing metabolic pathways have different temperature sensitivities. The results define the metabolic response to temperature on the metabolic pathway level and are of importance for understanding the cryopreservation of human platelets and more complex human cells used in cellular therapy.

biochemistry↗

bioRxiv2018

Visualizing metabolic network dynamics through time-series metabolomics data

New technologies have given rise to an abundance of -omics data, particularly metabolomics data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of new computational visualization methodologies. Here, we present a new method for the visualization of time-course metabolomics data within the context of metabolic network maps. We demonstrate the utility of this method by examining previously published data for two cellular systems--the human platelet and erythrocyte under cold storage for use in transfusion medicine.\n\nThe results comprise two animated videos that allow for new insights into the metabolic state of both cell types. In the case study of the platelet metabolome during storage, the new visualization technique elucidates a nicotinamide accumulation which mirrors that of hypoxanthine and might, therefore, reflect similar pathway usage. This visual analysis provides a possible explanation for why the salvage reactions in purine metabolism exhibit lower activity during the first few days of the storage period. The second case study displays drastic changes in specific erythrocyte metabolite pools at different times during storage at different temperatures.\n\nIn conclusion, this new visualization technique introduced in this article constitutes a well-suitable approach for large-scale network exploration and advances hypothesis generation. This method can be applied to any system with data and a metabolic map to promote visualization and understand physiology at the network level. More broadly, we hope that our approach will provide the blueprints for new visualizations of other longitudinal -omics data types.\n\nAUTHOR SUMMARYProfiling the dynamic state of a metabolic network through the use of time-course metabolomics technologies allows insights into cellular biochemistry. Interpreting these data together at the systems level provides challenges that can be addressed through the development of new visualization approaches. Here, we present a new method for the visualization of time-course metabolomics data that integrates data into an existing metabolic network map. In brief, the metabolomics data are visualized directly on a network map with dynamic elements (nodes that either change size, fill level, or color corresponding with the concentration) while the user controls the time series (i.e., which time point is being displayed) through a graphical interface. We provide short videos that illustrate the utility of this method through its application to existing data sets for the human platelet and erythrocyte. The results presented here give blueprints for the development of visualization methods for other time-course -omics data types that attempt to understand systems-level physiology.

systems biology↗