Multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) family transporters are essential in glycan synthesis, flipping lipid-linked precursors across cell membranes. Yet, how they select their substrates remains enigmatic. Here, we investigate the substrate specificity of the MOP transporters in the capsular polysaccharide (CPS) synthesis pathway in . These capsule flippases collectively transport more than 100 types of capsule precursors. To determine whether they can substitute for one another, we developed a high-throughput approach to systematically examine nearly 6000 combinations of flippases and substrates. CPS flippases fall into three groups: relaxed, type-specific, and strictly specific. Cargo size and CPS acetylation affect transport, and we isolated additional gain-of-function flippase variants that can substitute for the peptidoglycan flippase YtgP (MurJ). We also showed that combining flippase variants in a single cassette allows various CPS precursors to be flipped, which may aid glycoengineering. This study reveals that MOP flippases exhibit broad specificity, shaping the evolution of glycan synthesis.
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http://dx.doi.org/10.1126/sciadv.adr0162 | DOI Listing |
Inflamm Res
January 2025
Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina da Universidade do Porto (FMUP), Rua Dr. Plácido da Costa, S/N, Edifício Poente, Piso 3, 4200-450, Porto, Portugal.
Background And Aims: Endocan has been scarcely explored in COVID-19, especially regarding its modulation by veno-venous extracorporeal membrane oxygenation (VV-ECMO), hypertension or previous renin-angiotensin-aldosterone system (RAAS) inhibitors treatment. We compared endocan and other endotheliitis markers in hospitalized COVID-19 patients and assessed their modulation by VV-ECMO, hypertension and previous RAAS inhibitors treatment.
Material And Methods: Serum endocan, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were measured in "severe" (n = 27), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) COVID-19 patients at admission, days 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point.
Amino Acids
January 2025
Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
In recent years, the use of cationic peptides as alternative drugs with anticancer activity has received attention. In this study, the targeted release of curcumin (Cur) and CM11 peptide alone and together against hepatocellular carcinoma (HCC) was evaluated using chitosan nanoparticles (CS NPs) coated with Pres1 that target the SB3 antigen of HCC cells (PreS1-Cur-CM11-CS NPs). SB3 protein is the specific antigen of HCC and the PreS1 peptide is a part of the hepatitis B antigen, which can specifically bind to the SB3 protein.
View Article and Find Full Text PDFInflamm Res
January 2025
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC, 29425, USA.
Background: Sepsis-associated encephalopathy (SAE) often results from neuroinflammation. Recent studies have shown that brain platelet-derived growth factor receptor β (PDGFRβ) cells, including pericytes, may act as early sensors of infection by secreting monocyte chemoattractant protein-1 (MCP-1), which transmits inflammatory signals to the central nervous system. The erythroblast transformation-specific (ETS) transcription factor Friend leukemia virus integration 1 (Fli-1) plays a critical role in inflammation by regulating the expression of key cytokines, including MCP-1.
View Article and Find Full Text PDFInflamm Res
January 2025
Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, SAR, China.
Background: Sclerostin (SOST) is traditionally regarded as an osteocyte-derived secreted glycoprotein that regulates bone mineralization. Recent studies reported that SOST is also released from non-skeletal sources, especially during inflammation. However, the cellular source and regulatory mechanisms governing SOST generation in inflammation remain unclear.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Institute of Translational Medicine, Shanghai University, 200444 Shanghai, China.
Background: Dexamethasone has proven life-saving in severe acute respiratory syndrome (SARS) and COVID-19 cases. However, its systemic administration is accompanied by serious side effects. Inhalation delivery of dexamethasone (Dex) faces challenges such as low lung deposition, brief residence in the respiratory tract, and the pulmonary mucus barrier, limiting its clinical use.
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