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Integrated SegFlow, µSIA, and UPLC for Online Sialic Acid Quantitation of Glycoproteins Directly from Bioreactors.

Eng Life Sci

January 2025

Analytical Development & Analytical Attribute Science in Biologics Bristol Myers Squibb Devens Massachusetts USA.

This study emphasizes the critical importance of closely monitoring and controlling the sialic acid content in therapeutic glycoproteins, including EPO, interferon-γ, Orencia, Enbrel, and others, as the level of sialylation directly impacts their pharmacokinetics (PK), immunogenicity, potency, and overall clinical performance due to its influence on protein clearance via hepatic asialoglycoprotein receptors (ASGPR). The ASGPR recognizes and binds to glycoproteins exposed to terminal galactose or N-acetylgalactosamine residues, leading to receptor-mediated endocytosis. Recent studies have demonstrated that sialylation of O-linked glycan plays a role in protecting against macrophage galactose lectin (MGL)-mediated clearance.

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Unlabelled: Due to its natural influenza susceptibility, clinical signs, transmission, and similar sialic acid residue distribution, the ferret is the primary animal model for human influenza research. Antibodies generated following infection of ferrets with human influenza viruses are used in surveillance to detect antigenic drift and cross-reactivity with vaccine viruses and circulating strains. Inoculation of ferrets, with over 1,500 human clinical influenza isolates (1998-2019) resulted in lower antibody responses (HI <1:160) to 86% (387 out of 448) influenza B viruses (IBVs) compared to 2.

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Chronic hypereosinophilia, defined as persistent elevated blood levels of eosinophils ≥1,500/μL, is associated with tissue infiltration of eosinophils and consequent organ damage by eosinophil release of toxic mediators. The current therapies for chronic hypereosinophilia have limited success, require repetitive administration, and are associated with a variety of adverse effects. As a novel approach to treat chronic hypereosinophilia, we hypothesized that adeno-associated virus (AAV)-mediated delivery of an anti-human eosinophil antibody would provide one-time therapy that would mediate persistent suppression of blood eosinophil levels.

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Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are connective tissue autoimmune diseases. The present study aimed to check whether serum clusterin (CLU) concentration and its glycosylation pattern may be markers differentiating these diseases-blood sera of patients with PsA (n = 37), RA (n = 34), and healthy subjects (control, n = 21) were examined. CLU concentration was measured using the ELISA test.

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Article Synopsis
  • Malondialdehyde (MDA) is identified as a potential predictor of inhospital mortality in patients with acute coronary syndrome (ACS), a condition with limited research on this marker compared to stable angina pectoris.
  • The study involved 556 ACS patients, using leftover plasma samples to analyze various blood markers, including MDA, troponin, and others, in relation to inhospital mortality.
  • Results showed that MDA levels, along with age and creatine, were independent predictors of inhospital mortality, with an optimal MDA cutoff value of >33.1 providing high sensitivity (85%) and specificity (88.17%) for predicting outcomes.
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