5 research outputs found
Data_Sheet_2_Serum proteomic biomarker investigation of vascular depression using data-independent acquisition: a pilot study.docx
BackgroundVascular depression (VaD) is a depressive disorder closely associated with cerebrovascular disease and vascular risk factors. It remains underestimated owing to challenging diagnostics and limited information regarding the pathophysiological mechanisms of VaD. The purpose of this study was to analyze the proteomic signatures and identify the potential biomarkers with diagnostic significance in VaD.MethodsDeep profiling of the serum proteome of 35 patients with VaD and 36 controls was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Functional enrichment analysis of the quantified proteins was based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Reactome databases. Machine learning algorithms were used to screen candidate proteins and develop a protein-based model to effectively distinguish patients with VaD.ResultsThere were 29 up-regulated and 31 down-regulated proteins in the VaD group compared to the controls (|log2FC| ≥ 0.26, p ≤ 0.05). Enrichment pathways analyses showed that neurobiological processes related to synaptic vesicle cycle and axon guidance may be dysregulated in VaD. Extrinsic component of synaptic vesicle membrane was the most enriched term in the cellular components (CC) terms. 19 candidate proteins were filtered for further modeling. A nomogram was developed with the combination of HECT domain E3 ubiquitin protein ligase 3 (HECTD3), Nidogen-2 (NID2), FTO alpha-ketoglutarate-dependent dioxygenase (FTO), Golgi membrane protein 1 (GOLM1), and N-acetylneuraminate lyase (NPL), which could be used to predict VaD risk with favorable efficacy.ConclusionThis study offers a comprehensive and integrated view of serum proteomics and contributes to a valuable proteomics-based diagnostic model for VaD.</p
Data_Sheet_1_Serum proteomic biomarker investigation of vascular depression using data-independent acquisition: a pilot study.xlsx
BackgroundVascular depression (VaD) is a depressive disorder closely associated with cerebrovascular disease and vascular risk factors. It remains underestimated owing to challenging diagnostics and limited information regarding the pathophysiological mechanisms of VaD. The purpose of this study was to analyze the proteomic signatures and identify the potential biomarkers with diagnostic significance in VaD.MethodsDeep profiling of the serum proteome of 35 patients with VaD and 36 controls was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Functional enrichment analysis of the quantified proteins was based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Reactome databases. Machine learning algorithms were used to screen candidate proteins and develop a protein-based model to effectively distinguish patients with VaD.ResultsThere were 29 up-regulated and 31 down-regulated proteins in the VaD group compared to the controls (|log2FC| ≥ 0.26, p ≤ 0.05). Enrichment pathways analyses showed that neurobiological processes related to synaptic vesicle cycle and axon guidance may be dysregulated in VaD. Extrinsic component of synaptic vesicle membrane was the most enriched term in the cellular components (CC) terms. 19 candidate proteins were filtered for further modeling. A nomogram was developed with the combination of HECT domain E3 ubiquitin protein ligase 3 (HECTD3), Nidogen-2 (NID2), FTO alpha-ketoglutarate-dependent dioxygenase (FTO), Golgi membrane protein 1 (GOLM1), and N-acetylneuraminate lyase (NPL), which could be used to predict VaD risk with favorable efficacy.ConclusionThis study offers a comprehensive and integrated view of serum proteomics and contributes to a valuable proteomics-based diagnostic model for VaD.</p
Image_1_Serum proteomic biomarker investigation of vascular depression using data-independent acquisition: a pilot study.TIF
BackgroundVascular depression (VaD) is a depressive disorder closely associated with cerebrovascular disease and vascular risk factors. It remains underestimated owing to challenging diagnostics and limited information regarding the pathophysiological mechanisms of VaD. The purpose of this study was to analyze the proteomic signatures and identify the potential biomarkers with diagnostic significance in VaD.MethodsDeep profiling of the serum proteome of 35 patients with VaD and 36 controls was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Functional enrichment analysis of the quantified proteins was based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Reactome databases. Machine learning algorithms were used to screen candidate proteins and develop a protein-based model to effectively distinguish patients with VaD.ResultsThere were 29 up-regulated and 31 down-regulated proteins in the VaD group compared to the controls (|log2FC| ≥ 0.26, p ≤ 0.05). Enrichment pathways analyses showed that neurobiological processes related to synaptic vesicle cycle and axon guidance may be dysregulated in VaD. Extrinsic component of synaptic vesicle membrane was the most enriched term in the cellular components (CC) terms. 19 candidate proteins were filtered for further modeling. A nomogram was developed with the combination of HECT domain E3 ubiquitin protein ligase 3 (HECTD3), Nidogen-2 (NID2), FTO alpha-ketoglutarate-dependent dioxygenase (FTO), Golgi membrane protein 1 (GOLM1), and N-acetylneuraminate lyase (NPL), which could be used to predict VaD risk with favorable efficacy.ConclusionThis study offers a comprehensive and integrated view of serum proteomics and contributes to a valuable proteomics-based diagnostic model for VaD.</p
Image_2_Serum proteomic biomarker investigation of vascular depression using data-independent acquisition: a pilot study.TIF
BackgroundVascular depression (VaD) is a depressive disorder closely associated with cerebrovascular disease and vascular risk factors. It remains underestimated owing to challenging diagnostics and limited information regarding the pathophysiological mechanisms of VaD. The purpose of this study was to analyze the proteomic signatures and identify the potential biomarkers with diagnostic significance in VaD.MethodsDeep profiling of the serum proteome of 35 patients with VaD and 36 controls was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Functional enrichment analysis of the quantified proteins was based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Reactome databases. Machine learning algorithms were used to screen candidate proteins and develop a protein-based model to effectively distinguish patients with VaD.ResultsThere were 29 up-regulated and 31 down-regulated proteins in the VaD group compared to the controls (|log2FC| ≥ 0.26, p ≤ 0.05). Enrichment pathways analyses showed that neurobiological processes related to synaptic vesicle cycle and axon guidance may be dysregulated in VaD. Extrinsic component of synaptic vesicle membrane was the most enriched term in the cellular components (CC) terms. 19 candidate proteins were filtered for further modeling. A nomogram was developed with the combination of HECT domain E3 ubiquitin protein ligase 3 (HECTD3), Nidogen-2 (NID2), FTO alpha-ketoglutarate-dependent dioxygenase (FTO), Golgi membrane protein 1 (GOLM1), and N-acetylneuraminate lyase (NPL), which could be used to predict VaD risk with favorable efficacy.ConclusionThis study offers a comprehensive and integrated view of serum proteomics and contributes to a valuable proteomics-based diagnostic model for VaD.</p
Design, Synthesis, and Biological Evaluation of Mitochondria-Targeted Flavone–Naphthalimide–Polyamine Conjugates with Antimetastatic Activity
Approximately
90% of cancer-associated deaths result from disseminated tumors, indicating
the ineffectiveness of current therapies and the imperative need of
antimetastatic drugs. A novel pharmacophore with flavonoid and naphthalimide
moieties was constructed by using a fragment-based drug design and
a series of eight flavone–naphthalimide–polyamine conjugates
were synthesized. <i>In vitro</i> evaluation revealed that
compound <b>6c</b> with a homospermidine motif displayed better
cell selectivity between cancerous and normal liver cells than amonafide
did. The <i>in vivo</i> assays on two hepatocellular carcinoma
(HCC) models verified that <b>6c</b> potently suppressed pulmonary
metastasis with improved organ indexes compared to amonafide. Various
experiments showed that <b>6c</b> as a potential fluorescent
chemical probe could target the mitochondria. Preliminary investigation
into the mechanism of action of <b>6c</b> indicated that it
might harness a polyamine transporter for cell entrance, localize
in the mitochondria, selectively cause reactive oxygen species (ROS)
overproduction in hepatoma cells instead of normal liver cells, and
finally lead to HCC cell apoptosis and migration inhibition via multiple
ROS-mediated signaling pathways