Evidence map›Paper›PMID 39754871›Full record

ArticleBiomaterials advances2025

Examining structure-activity relationships of ManNAc analogs used in the metabolic glycoengineering of human neural stem cells.

Kris Dammen-Brower, Olivia Arbogast, Stanley Zhu, Chunfang Qiu, Cissy Zhang, Pratik Khare, Anne Le, Xiaofeng Jia, Kevin J Yarema

Abstract read
In one paragraph

Article in Biomaterials advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Balancing inflammation and regeneration: immune cell dynamics in nerve repair: a comprehensive review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Kris Dammen-BrowerDepartment of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Whiting School of Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Olivia ArbogastDepartment of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Whiting School of Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Stanley ZhuDepartment of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Whiting School of Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Chunfang QiuDepartment of Neurosurgery, School of Medicine, University of Maryland, Baltimore, MD, USA.
Cissy ZhangDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA; Gigantest Inc, 31 Light Street, Baltimore, MD, USA.
Pratik KhareDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA; Gigantest Inc, 31 Light Street, Baltimore, MD, USA.
Anne LeGigantest Inc, 31 Light Street, Baltimore, MD, USA.
Xiaofeng JiaDepartment of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA; Department of Neurosurgery, School of Medicine, University of Maryland, Baltimore, MD, USA; Department of Orthopedics, School of Medicine, University of Maryland, Baltimore, MD, USA; Department of Anatomy and Neurobiology, School of Medicine, University of Maryland, Baltimore, MD, USA. Electronic address: xjia@som.umaryland.edu.
Kevin J YaremaDepartment of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Whiting School of Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: kyarema1@jhu.edu.

Funding

Stem Cell Surface Modification to Promote Nerve RegenerationR01NS117102 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI Xiaofeng Jia · 2021 to 2026
$2.0M
Improving Brain Recovery Through GlycoengineeringR01NS125232 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI Xiaofeng Jia · 2022 to 2026
$2.0M
Brain Recovery after Cardiac Arrest with Metabolic Glycoengineered Stem CellsR01NS110387 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI JIA, XIAOFENG · 2018 to 2022
$1.7M
NINDS NIH HHS R01 NS110387NINDS NIH HHS R01 NS117102NINDS NIH HHS R01 NS125232
6 · The paper itself

Abstract

This study defines biochemical mechanisms that contribute to novel neural-regenerative activities we recently demonstrated for thiol-modified ManNAc analogs in human neural stem cells (hNSCs) by comparing our lead drug candidate for brain repair, "TProp," to a "size-matched" N-alkyl control analog, "But." These analogs biosynthetically install non-natural sialic acids into cell surface glycans, altering cell surface receptor activity and adhesive properties of cells. In this study, TProp modulated sialic acid-related biology in hNSCs to promote neuronal differentiation through modulation of cell adhesion molecules (integrins α6, β1, E-cadherin, and PSGL-1) and stem cell markers. By comparison, But elicited minimal change to these endpoints, indicating dependence on the chemical properties of the thiol group of non-natural sialic acids and not the size of this sugar's N-acyl group. Conversely, But elicited distinct intracellular responses including increased nestin expression (~6-fold) and the modulation of several metabolites identified through cell-wide screening. Metabolites up-regulated by But included dopamine and norfenenfrine, suggesting that this analog may be a drug candidate for treating neural damage associated with conditions such as Parkinson's disease. The metabolomics data also provided new insights into the neuroprotective effects of TProp when used to treat brain injury by upregulation of anti-inflammatory metabolites (e.g., α- & γ-linolenic acids) valuable for dampening injury- and treatment-related inflammation. Finally, these analogs modulate compounds that control proline (e.g., 1-pyrroline-2-carboxylate), a master regulator of many cellular activities. Overall, this study presents new mechanisms and pathways to exploit metabolic glycoengineering for neural repair and treatment of neurodegenerative diseases.

Indexed as

Metabolic EngineeringNeural Stem CellsCell DifferentiationHumansSialic AcidsStructure-Activity RelationshipSialic AcidsAlkyl-modified sialic acidsManNAc analogsMetabolic glycoengineeringNeural stem cellsStem cell metabolismThiol-modified sialic acids

Identifiers

PMID39754871
PMCPMC11884250

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.