An Activity‐Based Nanosensor for Minimally‐Invasive Measurement of Protease Activity in Traumatic Brain Injury

Kudryashev, Julia A.; Madias, Marianne I.; Kandell, Rebecca M; Lin, Queenie X.; Kwon, Ester J.

doi:10.1002/adfm.202300218

Cited by 3 publications

(1 citation statement)

References 70 publications

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“…Curiously, ABPP has not yet been explored in human TBI samples for the development of diagnostic tools or eventual drug targets based on the biological activity of enzymes following TBI. Yet, the single protease activity of thrombin[6] or calpain 1 has already been explored via specific substrates or activity based sensors[10, 29], confirming that enzyme biological activity, but not protein abundance, plays a key role in molecular changes shortly after brain trauma. Currently, profiling of enzyme activity states by large-scale ABPP is usually performed in full cell lysates or in tissue homogenates[13, 23, 30] at physiological pH.…”

Section: Article Type: Rapid Communicationsmentioning

confidence: 99%

Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma

Maret,

Wiskott,

Shipley

et al. 2024

Preprint

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Purpose: Traumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial haemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes. Experimental design: Serine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation and neuronal signaling. Here we investigated activity-based protein profiling (ABPP) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS). Results: Our proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism Conclusions and clinical relevance: To our knowledge, this is the first study to investigate the ABPP of the SHs enzyme family to detect changes in their physiological activity in blood serum in severe TBI. We used antemortem (AM) serum from infants under the age of 2 years who were victims of AHT with a severe form of ICH. The analytical approach used in the proof-of-principle study shows reduced activities of serum serine lipases in AHT cases and could be further investigated in mild forms of AHT, which currently show 30% of misdiagnosed cases in clinics.

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Section: Article Type: Rapid Communicationsmentioning

confidence: 99%

Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma

Maret,

Wiskott,

Shipley

et al. 2024

Preprint

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Specific and Magnetic Covalent Organic Framework Confined Os Nanoclusterzyme for Interference‐Free and Ultrasensitive Biosensing

Zhou,

Dai,

Lin

et al. 2024

Adv Funct Materials

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The peroxidase (POD)‐mimic nanozymes can be a potential tool for point‐of‐care (POC) diseases diagnosis. However, the complex sample matrix and unspecific multiple‐enzyme activities of nanozyme can generate false background signal and decrease the diagnostic accuracy. Here, a magnetic and POD‐specific covalent organic framework (COF) confined osmium (Os) nanoclusterzyme Fe3O4@COF@Os is developed for biomarkers biosensing. First, found that the catalytic activity and specificity of Fe3O4@COF@Os can be regulated by the deoxidizers and the functional groups of COF ligands. By using ascorbic acid as deoxidizer and F functional COF ligands, Fe3O4@COF@Os displayed superior POD‐specific activity and negligible oxidase (OXD) and catalase (CAT) mimic activity. Therefore, Fe3O4@COF@Os can separate and analyze of targets in bio‐matrix without background interference. For application, Fe3O4@COF@Os based lateral flow assay is established for serum cancer biomarker prostate‐specific antigen, the detection limit is 3.83 pg mL−1. For clinical prostatic cancer samples, the accuracy is 100% with a correlation coefficient of 0.998 with commercial ELISA kit. For chronic disease biomarker sensing, salivary glucose can be quantified as low as 0.1 µm, with negligible background interference and favorable recyclability. This specific magnetic nanozymes can offer a promising pretreatment‐free and POC strategy for rapid and accurate diseases diagnosis.

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Microenvironment‐Responsive Hydrogel Reduces Seizures After Traumatic Brain Injury in Juvenile Rats by Reducing Oxidative Stress and Hippocampal Inflammation

Han,

Zhao,

et al. 2024

Macromolecular Bioscience

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Traumatic brain injury (TBI) is the primary cause of child mortality and disability worldwide. It can result in severe complications that significantly impact children's quality of life, including post‐traumatic epilepsy (PTE). An increasing number of studies suggest that TBI‐induced oxidative stress and neuroinflammatory sequelae (especially inflammation in the hippocampus region) may lead to the development of PTE. Due to the blood‐brain barrier (BBB), typical systemic pharmacological therapy for TBI cannot deliver berberine (BBR) to the targeted location in the early stages of the injury, although BBR has strong anti‐inflammatory properties. To break through this limitation, we developed a microenvironment‐responsive Gelatin methacrylate hydrogel (GM/PB) to deliver BBR for regulating neuroinflammatory reactions and removing ROS in the brain trauma microenvironment through poly(propylene sulfide)60 (PPS60). In situ injection of the GM/PB hydrogel efficiently bypassed the BBB and was administered directly to the surface of brain tissue. In post‐traumatic brain injury models, GM/PB has the potential to mitigate oxidative stress and neuroinflammatory responses, facilitate functional recovery, and lessen seizing. These findings could lead to a new treatment for brain injuries that minimizes complications and improves the quality of life.This article is protected by copyright. All rights reserved

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An Activity‐Based Nanosensor for Minimally‐Invasive Measurement of Protease Activity in Traumatic Brain Injury

Cited by 3 publications

References 70 publications

Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma

Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma

Specific and Magnetic Covalent Organic Framework Confined Os Nanoclusterzyme for Interference‐Free and Ultrasensitive Biosensing

Microenvironment‐Responsive Hydrogel Reduces Seizures After Traumatic Brain Injury in Juvenile Rats by Reducing Oxidative Stress and Hippocampal Inflammation

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