Nanopore discrimination and sensitive plasma detection of multiple natriuretic peptides: The representative biomarker of human heart failure

Zhang, Shaoxia; Wang, Yunjiao; Song, Dandan; Guan, Sarah; Zhou, Daming; Gong, Linyu; Liang, Liyuan; Guan, Xiyun; Wang, Liang

doi:10.1016/j.bios.2023.115299

Cited by 8 publications

(5 citation statements)

References 54 publications

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“…Nanopore technology is a convenient single-molecule technique with major advantages of high throughput, high sensitivity, and easy operation, which has been used in detecting biomolecules, such as DNA or RNA, − peptides, − and proteins. − In decades, the adaptor-assistant nanopore method has been developed to sense smaller analytes, such as metal ions and organic molecules. − For example, β-cyclodextrin (β-CD), as the most commonly used adaptor, can reside in the α-hemolysin (α-HL) nanopore and reversibly host the small molecules to generate detectable signals to recognize drug molecules and toxic molecules. − The amantadine and its acetylation product, acetylamantadine, both cause secondary signals due to the strong host–guest interactions of β-CD, making it hard to detect the desired analyte with excessive the other . So, the β-CD-assistant nanopore is not suitable for the quantification of acetylamantadine in cancer patient urine samples due to the existence of excess amantadine caused by its incomplete transformation .…”

Section: Introductionmentioning

confidence: 99%

Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis

Yin,

Yang,

Song

et al. 2024

Anal. Chem.

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The high expression of Spermidine/spermine N 1-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported β-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host–guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.

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Section: Introductionmentioning

confidence: 99%

Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis

Yin,

Yang,

Song

et al. 2024

Anal. Chem.

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“…Examples include detection of DNA sequences containing methylcytosine, natriuretic peptides, and mutant hemoglobin proteins in biofluids such as serum or blood. 37,49,50 The protein nanopore, aerolysin (Figure 1c), has long been used to sense and characterize a variety of biomolecules, including biomarkers, 9,11 and reviewed in ref 1. More recently, ; and a representative histogram of the average blockade fraction against number of events (c).…”

Section: Introductionmentioning

confidence: 99%

“…This method has been used to detect thyroid-stimulating hormone, prostate antigen (PSA), carcinogenic embryonic antigen, and HIV p24 in serum. − Alternative assays have used binding partners to indirectly sense SARS-CoV-2 spike protein, PSA, EGF, C-reactive protein, thrombin, vascular endothelial growth factor, glucose, asparagine, or thiamine, without purification, directly in biofluids, such as plasma, serum, saliva, sweat, or urine. − Additional studies have indirectly detected biomarker enzyme activity such as alkaline phosphatase or botulinum toxin in biofluids. , Far fewer studies have attempted to directly detect analytes in biofluids, reflecting the challenging nature of this type of assay. Examples include detection of DNA sequences containing methylcytosine, natriuretic peptides, and mutant hemoglobin proteins in biofluids such as serum or blood. ,, …”

Section: Introductionmentioning

confidence: 99%

Identification of Conformational Variants for Bradykinin Biomarker Peptides from a Biofluid Using a Nanopore and Machine Learning

Greive,

Bacri,

Cressiot

et al. 2023

ACS Nano

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There is a current need to develop methods for the sensitive detection of peptide biomarkers in complex mixtures of molecules, such as biofluids, to enable early disease detection. Moreover, to our knowledge, there is currently no detection method capable of identifying the different conformations of a peptide biomarker differing by a single amino acid. Single-molecule nanopore sensing promises to provide this level of resolution. In order to be able to identify these differences in a biofluid such as serum, it is necessary to carefully characterize electrical parameters to obtain specific signatures of each biomarker population observed. We are interested here in a family of peptide biomarkers, kinins such as bradykinin and des-Arg9 bradykinin, that are involved in many disabling pathologies (allergy, asthma, angioedema, sepsis, or cancer). We show the proof of concept for direct identification of these biomarkers in serum at the single-molecule level using a protein nanopore. Each peptide exhibits two unique electrical signatures attributed to specific conformations in bulk. The same signatures are found in serum, allowing their discrimination and identification in a complex mixture such as biofluid. To extend the utility of our experimental results, we developed a principal component analysis approach to define the most relevant electrical parameters for their identification. Finally, we used semisupervised classification to assign each event type to a specific biomarker at physiological serum concentration. In the future, single-molecule scale analysis of peptide biomarkers using a powerful nanopore coupled with machine learning will facilitate the identification and quantification of other clinically relevant biomarkers from biofluids.

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“…When a patient experiences heart failure, as the severity of the condition increases, their cardiac volume load or pressure load will also increase, and the concentration of BNP in the blood will correspondingly increase [ 12 ]. Therefore, BNP levels in heart failure patients will increase with the severity of the disease and BNP is a sensitive indicator for diagnosing heart failure and can independently predict the elevation of left ventricular end-diastolic pressure, serving as a better indicator for predicting the condition of heart failure [ 16 ]. In the 2004 American expert consensus, the value of NT-pro-BNP was also affirmed and NT-pro-BNP < 300 pg/ml can exclude heart failure, with a negative predictive value of 99% [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of continuous positive airway pressure on NT-pro-BNP in obstructive sleep apnea patients: a meta-analysis

Wang

et al. 2023

BMC Pulm Med

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Background N-terminal probrain natriuretic peptide (NT-pro-BNP) and BNP are well-known markers for the diagnosis and prognostic of heart failure. Until now, it was not clear whether BNP levels are influenced by events occurring within Obstructive sleep apnea–hypopnea syndrome (OSAHS) with continuous positive airway pressure (CPAP). Methods A thorough search in PubMed, EMBASE, Google Scholar, and Web of Science databases up to October 24, 2022, and a meta-analysis aimed to explore further accurate estimates of the effects of BNP on OSAHS after CPAP treatment to assess the strength of the evidence. Results The forest plot outcome indicated that CPAP therapy did not change the BNP level in patients with OSAHS, with a weighted mean difference (WMD) of -0.47 (95% CI: -1.67 to 2.62; P = 0.53] based on the random effect model because of high significant heterogeneity (I2 = 80%) among the studies. Subgroup analysis also explored the changes in BNP levels in patients with OSAHS. Begg’s test (P = 0.835) and Egger’s test (P = 0.245) suggested significant negative publication bias. Conclusion Our meta-analysis suggests that CPAP therapy does not change the BNP level in patients with OSAHS; therefore, it is not accurate to use BNP level as an index to evaluate heart function in patients with OSAHS, but more related research should be conducted.

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Nanopore discrimination and sensitive plasma detection of multiple natriuretic peptides: The representative biomarker of human heart failure

Cited by 8 publications

References 54 publications

Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis

Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis

Identification of Conformational Variants for Bradykinin Biomarker Peptides from a Biofluid Using a Nanopore and Machine Learning

Efficacy of continuous positive airway pressure on NT-pro-BNP in obstructive sleep apnea patients: a meta-analysis

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