Proteomics and Metabolomics in Biomedicine, 2nd Volume

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12 pages, 1331 KiB

Open AccessArticle

Development of an LC–TOF/MS Method to Quantify Camrelizumab in Human Serum

by Li Song, Yan Liang, Yilin Li, Tingting Guo, Hui Li and Shuxuan Liang

Molecules 2024, 29(20), 4862; https://doi.org/10.3390/molecules29204862 - 14 Oct 2024

Viewed by 632

Abstract

With the advantages of a high specificity, a long half-life, and a high safety, the use of antibody biologic drugs, including camrelizumab, has been rapidly increasing in clinical practice. Camrelizumab, an immune checkpoint inhibitor and humanized monoclonal antibody, is used to treat several advanced solid cancers. Measuring its concentration supports personalized dosage adjustments, influences treatment decisions for patients, strengthens the control of disease activity through therapeutic drug monitoring, and helps evaluate and prevent drug interactions in combination therapy. Because antibodies are present in complex biological matrices, quantifying monoclonal antibody drugs is challenging, and must rely on precise, selective, and reliable analytical methods. In this study, a quadrupole time-of-flight mass spectrometry TripleTOF 6600+ (AB SCIEX, Framingham, MA, USA) system equipped with a Turbo V ion source was used for the qualitative analysis of monoclonal antibodies using the data-dependent acquisition (IDA) MS/MS mode, followed by quantitative analysis using a targeted MRMHR workflow. This method showed a good linear relationship within the range of 4–160 μg/mL, with a correlation coefficient of R² ≥ 0.996. It demonstrated an acceptable accuracy (88.95–101.18%) and precision (≤15%). Furthermore, the lower limit of quantification was found to be 4 μg/mL, with the lowest detection limit of 0.3217 μg/mL, indicating that this method is rapid, accurate, and reliable for the quantitative analysis of camrelizumab in human serum. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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12 pages, 4636 KiB

Open AccessArticle

Circulating Factors as Potential Biomarkers of Cardiovascular Damage Progression Associated with Type 2 Diabetes

by Giovanni Sartore, Francesco Piarulli, Eugenio Ragazzi, Alice Mallia, Stefania Ghilardi, Massimo Carollo, Annunziata Lapolla and Cristina Banfi

Proteomes 2024, 12(4), 29; https://doi.org/10.3390/proteomes12040029 - 11 Oct 2024

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Abstract

Background: Diabetes, particularly type 2 diabetes (T2D), is linked with an increased risk of developing coronary heart disease (CHD). The present study aimed to evaluate potential circulating biomarkers of CHD by adopting a targeted proteomic approach based on proximity extension assays (PEA). Methods: The study was based on 30 patients with both T2D and CHD (group DC), 30 patients with T2D without CHD (group DN) and 29 patients without diabetes but with a diagnosis of CHD (group NC). Plasma samples were analyzed using PEA, with an Olink Target 96 cardiometabolic panel expressed as normalized protein expression (NPX) units. Results: Lysosomal Pro-X carboxypeptidase (PRCP), Liver carboxylesterase 1 (CES1), Complement C2 (C2), and Intercellular adhesion molecule 3 (ICAM3) were lower in the DC and NC groups compared with the DN groups. Lithostathine-1-alpha (REG1A) and Immunoglobulin lambda constant 2 (IGLC2) were found higher in the DC group compared to DN and NC groups. ROC analysis suggested a significant ability of the six proteins to distinguish among the three groups (whole model test p < 0.0001, AUC 0.83–0.88), with a satisfactory discriminating performance in terms of sensitivity (77–90%) and specificity (70–90%). A possible role of IGLC2, PRCP, and REG1A in indicating kidney impairment was found, with a sensitivity of 92% and specificity of 83%. Conclusions: The identified panel of six plasma proteins, using a targeted proteomic approach, provided evidence that these parameters could be considered in the chronic evolution of T2D and its complications. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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17 pages, 7241 KiB

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Comparative Proteomics and Metabonomics Analysis of Different Diapause Stages Revealed a New Regulation Mechanism of Diapause in Loxostege sticticalis (Lepidoptera: Pyralidae)

by Lijun Shao, Fangzheng Yue, Jinfu Fan, Qin Su, Hairui Liu, Quanyi Zhang and Linbo Xu

Molecules 2024, 29(15), 3472; https://doi.org/10.3390/molecules29153472 - 25 Jul 2024

Viewed by 1058

Abstract

Histone acetylation is an important epigenetic mechanism that has been shown to play a role in diapause regulation. To explore the physiological and molecular mechanisms of histone deacetylase in the diapause process, LC-MS/MS analysis was used to perform TMT proteomic and metabolomic analysis on non-diapause (ND), pre-diapause (PreD), diapause (D), cold treatment (CT), and post-diapause (RD) stages of the meadow moth. A total of 5367 proteins were identified by proteomics, including 1179 differentially expressed proteins. We found 975 (602 up-regulated and 373 down-regulated), 997 (608 up-regulated and 389 down-regulated), 1119 (726 up-regulated and 393 down-regulated), 1179 (630 up-regulated and 549 down-regulated), 94 (51 up-regulated and 43 down-regulated), 111 (63 up-regulated and 48 down-regulated), 533 (243 up-regulated and 290 down-regulated), 58 (31 up-regulated and 27 down-regulated), and 516 (228 up-regulated and 288 down-regulated) proteins in ND and PreD, ND and D, ND and CT, ND and RD, PreD and D, PreD and CT, PreD and RD, D and CT, D and RD, and CT and RD stages, respectively. A total of 1255 differentially expressed metabolites were annotated by metabolomics. Through KEGG analysis and time series analysis of differentially expressed metabolites, we found that phospholipids were annotated in significantly different modules, demonstrating their important role in the diapause process of the meadow moth. Using phospholipids as an indicator for weighted gene co-expression network analysis, we analyzed the most relevant differentially expressed proteins in the module and found that ribosomal 40s and 60s subunits were the most relevant proteins for diapause. Because there have been studies that have shown that histone deacetylase is associated with the diapause of meadow moths, we believe that histone deacetylase regulates the 40s and 60s subunits of ribosomes, which in turn affects the diapause of meadow moths. This finding expands our understanding of the regulation of meadow moth diapause and provides new insights into its control mechanism. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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15 pages, 2633 KiB

Open AccessArticle

Lipidomics Analysis Unravels Aberrant Lipid Species and Pathways Induced by Zinc Oxide Nanoparticles in Kidney Cells

by Boyun Kim, Gaeun Kim, Hyun Pyo Jeon and Jewon Jung

Int. J. Mol. Sci. 2024, 25(8), 4285; https://doi.org/10.3390/ijms25084285 - 12 Apr 2024

Cited by 3 | Viewed by 1142

Abstract

Zinc oxide nanoparticles (ZnO NPs) are widely used in versatile applications, from high technology to household products. While numerous studies have examined the toxic gene profile of ZnO NPs across various tissues, the specific lipid species associated with adverse effects and potential biomarkers remain elusive. In this study, we conducted a liquid chromatography-mass spectrometry based lipidomics analysis to uncover potential lipid biomarkers in human kidney cells following treatment with ZnO NPs. Furthermore, we employed lipid pathway enrichment analysis (LIPEA) to elucidate altered lipid-related signaling pathways. Our results demonstrate that ZnO NPs induce cytotoxicity in renal epithelial cells and modulate lipid species; we identified 64 lipids with a fold change (FC) > 2 and p < 0.01 with corrected p < 0.05 in HK2 cells post-treatment with ZnO NPs. Notably, the altered lipids between control HK2 cells and those treated with ZnO NPs were associated with the sphingolipid, autophagy, and glycerophospholipid pathways. This study unveils novel potential lipid biomarkers of ZnO NP nanotoxicity, representing the first lipidomic profiling of ZnO NPs in human renal epithelial cells. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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14 pages, 768 KiB

Open AccessReview

Proteoform Analysis of the Human Olfactory System: A Window into Neurodegenerative Diseases

by Eqrem Rusi, Fiorenza Pennacchia, Wael Abu Ruqa, Giuseppina Talarico, Giuseppe Bruno, Antonio Minni and Christian Barbato

Proteomes 2024, 12(1), 9; https://doi.org/10.3390/proteomes12010009 - 21 Mar 2024

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Abstract

Background: Very little is known about the proteome of the human olfactory system and how diseases associated with olfactory dysfunctions can affect it. With this review, we try to summarize the existing literature on the use of this technique for a better understanding of the neurodegenerative disease process. Methods: We used the PubMed database and found different articles which were then selected independently by three authors. Results: We found 157 articles, of which, after careful selection, only 30 were analyzed in this review. We presented all the associations identified between the protein/pathway alterations neurodegenerative diseases and SARS-CoV-2 infection. Conclusions: We think that the proteome of the olfactory system through blood, saliva, and mucus analysis could be a new way to better understand, diagnose, and finally treat neurodegenerative diseases. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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14 pages, 6239 KiB

Open AccessArticle

Proteomic Profiling of Early Secreted Proteins in Response to Lipopolysaccharide-Induced Vascular Endothelial Cell EA.hy926 Injury

by Worawat Songjang, Nitchawat Paiyabhroma, Noppadon Jumroon, Arunya Jiraviriyakul, Nitirut Nernpermpisooth, Porrnthanate Seenak, Sarawut Kumphune, Siriwan Thaisakun, Narumon Phaonakrop, Sittiruk Roytrakul and Panyupa Pankhong

Biomedicines 2023, 11(11), 3065; https://doi.org/10.3390/biomedicines11113065 - 15 Nov 2023

Cited by 4 | Viewed by 2404

Abstract

Sepsis is a crucial public health problem with a high mortality rate caused by a dysregulated host immune response to infection. Vascular endothelial cell injury is an important hallmark of sepsis, which leads to multiple organ failure and death. Early biomarkers to diagnose sepsis may provide early intervention and reduce risk of death. Damage-associated molecular patterns (DAMPs) are host nuclear or cytoplasmic molecules released from cells following tissue damage. We postulated that DAMPs could potentially be a novel sepsis biomarker. We used an in vitro model to determine suitable protein–DAMPs biomarkers for early sepsis diagnosis. Low and high lipopolysaccharide (LPS) doses were used to stimulate the human umbilical vein endothelial cell line EA.hy926 for 24, 48, and 72 h. Results showed that cell viability was reduced in both dose-dependent and time-dependent manners. Cell injury was corroborated by a significant increase in lactate dehydrogenase (LDH) activity within 24 h in cell-conditioned medium. Secreted protein–DAMPs in the supernatant, collected at different time points within 24 h, were characterized using shotgun proteomics LC-MS/MS analysis. Results showed that there were 2233 proteins. Among these, 181 proteins from the LPS-stimulated EA.hy926 at 1, 12, and 24 h were significantly different from those of the control. Twelve proteins were up-regulated at all three time points. Furthermore, a potential interaction analysis of predominant DAMPs-related proteins using STITCH 5.0 revealed the following associations with pathways: response to stress; bacterium; and LPS (GO:0080134; 0009617; 0032496). Markedly, alpha-2-HS-glycoprotein (AHSG or fetuin-A) and lactotransferrin (LTF) potentially presented since the first hour of LPS stimulation, and were highly up-regulated at 24 h. Taken together, we reported proteomic profiling of vascular endothelial cell-specific DAMPs in response to early an in vitro LPS stimulation, suggesting that these early damage-response protein candidates could be novel early biomarkers associated with sepsis. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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17 pages, 3059 KiB

Open AccessArticle

Metabolic Fingerprints of Effective Fluoxetine Treatment in the Prefrontal Cortex of Chronically Socially Isolated Rats: Marker Candidates and Predictive Metabolites

by Dragana Filipović, Julica Inderhees, Alexandra Korda, Predrag Tadić, Markus Schwaninger, Dragoš Inta and Stefan Borgwardt

Int. J. Mol. Sci. 2023, 24(13), 10957; https://doi.org/10.3390/ijms241310957 - 30 Jun 2023

Cited by 4 | Viewed by 1718

Abstract

The increasing prevalence of depression requires more effective therapy and the understanding of antidepressants’ mode of action. We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography–high resolution mass spectrometry. The behavioral phenotype was assessed by the forced swim test. To analyze the metabolomics data, we employed univariate and multivariate analysis and biomarker capacity assessment using the receiver operating characteristic (ROC) curve. We also identified the most predictive biomarkers using a support vector machine with linear kernel (SVM-LK). Upregulated myo-inositol following CSIS may represent a potential marker of depressive phenotype. Effective fluoxetine treatment reversed depressive-like behavior and increased sedoheptulose 7-phosphate, hypotaurine, and acetyl-L-carnitine contents, which were identified as marker candidates for fluoxetine efficacy. ROC analysis revealed 4 significant marker candidates for CSIS group discrimination, and 10 for fluoxetine efficacy. SVM-LK with accuracies of 61.50% or 93.30% identified a panel of 7 or 25 predictive metabolites for depressive-like behavior or fluoxetine effectiveness, respectively. Overall, metabolic fingerprints combined with the ROC curve and SVM-LK may represent a new approach to identifying marker candidates or predictive metabolites for ongoing disease or disease risk and treatment outcome. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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12 pages, 1162 KiB

Open AccessArticle

LC/MS-Based Untargeted Metabolomics Study in Women with Nonalcoholic Steatohepatitis Associated with Morbid Obesity

by Laia Bertran, Jordi Capellades, Sonia Abelló, Joan Durán-Bertran, Carmen Aguilar, Salomé Martinez, Fàtima Sabench, Xavier Correig, Oscar Yanes, Teresa Auguet and Cristóbal Richart

Int. J. Mol. Sci. 2023, 24(12), 9789; https://doi.org/10.3390/ijms24129789 - 6 Jun 2023

Cited by 1 | Viewed by 2090

Abstract

This study investigated the importance of a metabolomic analysis in a complex disease such as nonalcoholic steatohepatitis (NASH) associated with obesity. Using an untargeted metabolomics technique, we studied blood metabolites in 216 morbidly obese women with liver histological diagnosis. A total of 172 patients were diagnosed with nonalcoholic fatty liver disease (NAFLD), and 44 were diagnosed with normal liver (NL). Patients with NAFLD were classified into simple steatosis (n = 66) and NASH (n = 106) categories. A comparative analysis of metabolites levels between NASH and NL demonstrated significant differences in lipid metabolites and derivatives, mainly from the phospholipid group. In NASH, there were increased levels of several phosphatidylinositols and phosphatidylethanolamines, as well as isolated metabolites such as diacylglycerol 34:1, lyso-phosphatidylethanolamine 20:3 and sphingomyelin 38:1. By contrast, there were decreased levels of acylcarnitines, sphingomyelins and linoleic acid. These findings may facilitate identification studies of the main pathogenic metabolic pathways related to NASH and may also have a possible applicability in a panel of metabolites to be used as biomarkers in future algorithms of the disease diagnosis and its follow-up. Further confirmatory studies in groups with different ages and sexes are necessary. Full article

(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)

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Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	3.9	5.2	2013	15.3 Days	CHF 2600
International Journal of Molecular Sciences ijms	4.9	8.1	2000	18.1 Days	CHF 2900
Metabolites metabolites	3.4	5.7	2011	13.9 Days	CHF 2700
Molecules molecules	4.2	7.4	1996	15.1 Days	CHF 2700
Proteomes proteomes	4.0	6.5	2013	34.2 Days	CHF 1800

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