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TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequences
Tea Govednik, Duško Lainšček, Urška Kuhar, Marva Lachish, Sandra Janežič, Malan Štrbenc, Uroš Krapež, Roman Jerala, Daphne Atlas, Mateja Manček Keber, 2024, izvirni znanstveni članek

Povzetek: After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19.
Ključne besede: SARS-CoV-2, Disulfides, Thiol-reacting compound, Spike, Anti-inflammatory activity
Objavljeno v DiRROS: 06.02.2024; Ogledov: 103; Prenosov: 42
.pdf Celotno besedilo (7,11 MB)
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Developing an implicit solvation machine learning model for molecular simulations of ionic media
Amaury Coste, Ema Slejko, Julija Zavadlav, Matej Praprotnik, 2024, izvirni znanstveni članek

Objavljeno v DiRROS: 25.01.2024; Ogledov: 106; Prenosov: 59
.pdf Celotno besedilo (3,87 MB)
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A sodium/potassium switch for G4-prone G/C-rich sequences
Yu Luo, Martina Lenarčič Živković, Jiawei Wang, Jan Ryneš, Silvie Foldynová-Trantírková, Lukáš Trantírek, Daniela Verga, Jean-Louis Mergny, 2024, izvirni znanstveni članek

Objavljeno v DiRROS: 16.01.2024; Ogledov: 137; Prenosov: 62
.pdf Celotno besedilo (2,17 MB)
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Exploration of macromolecular phenotype of human skeletal muscle in diabetes using infrared spectroscopy
Barbara Zupančič, Chiedozie Kenneth Ugwoke, Mohamed Elwy Abdelmonaem, Armin Alibegović, Erika Cvetko, Jože Grdadolnik, Anja Šerbec, Nejc Umek, 2023, izvirni znanstveni članek

Povzetek: Introduction: The global burden of diabetes mellitus is escalating, and more efficient investigative strategies are needed for a deeper understanding of underlying pathophysiological mechanisms. The crucial role of skeletal muscle in carbohydrate and lipid metabolism makes it one of the most susceptible tissues to diabetes-related metabolic disorders. In tissue studies, conventional histochemical methods have several technical limitations and have been shown to inadequately characterise the biomolecular phenotype of skeletal muscle to provide a holistic view of the pathologically altered proportions of macromolecular constituents. Materials and methods: In this pilot study, we examined the composition of five different human skeletal muscles from male donors diagnosed with type 2 diabetes and non-diabetic controls. We analysed the lipid, glycogen, and collagen content in the muscles in a traditional manner with histochemical assays using different staining techniques. This served as a reference for comparison with the unconventional analysis of tissue composition using Fourier-transform infrared spectroscopy as an alternative methodological approach. Results: A thorough chemometric post-processing of the infrared spectra using a multi-stage spectral decomposition allowed the simultaneous identification of various compositional details from a vibrational spectrum measured in a single experiment. We obtained multifaceted information about the proportions of the different macromolecular constituents of skeletal muscle, which even allowed us to distinguish protein constituents with different structural properties. The most important methodological steps for a comprehensive insight into muscle composition have thus been set and parameters identified that can be used for the comparison between healthy and diabetic muscles. Conclusion: We have established a methodological framework based on vibrational spectroscopy for the detailed macromolecular analysis of human skeletal muscle that can effectively complement or may even serve as an alternative to histochemical assays. As this is a pilot study with relatively small sample sets, we remain cautious at this stage in drawing definitive conclusions about diabetes-related changes in skeletal muscle composition. However, the main focus and contribution of our work has been to provide an alternative, simple and efficient approach for this purpose. We are confident that we have achieved this goal and have brought our methodology to a level from which it can be successfully transferred to a large-scale study that allows the effects of diabetes on skeletal muscle composition and the interrelationships between the macromolecular tissue alterations due to diabetes to be investigated.
Ključne besede: diabetes mellitus, skeletal muscle, metabolism, macromulecular composition, infrared spectroscopy, multivariate analysis, histochemical assays
Objavljeno v DiRROS: 11.01.2024; Ogledov: 145; Prenosov: 59
.pdf Celotno besedilo (1,71 MB)
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