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13 pages, 17127 KiB

Open AccessArticle

Utilizing Proteomic Approaches to Uncover the Neuroprotective Effects of ACE Inhibitors: Implications for Alzheimer’s Disease Treatment

by Ming-Hui Yang, Tzu-Chuan Ho, Chin-Chuan Chang, Yuh-Shan Su, Cheng-Hui Yuan, Kuo-Pin Chuang and Yu-Chang Tyan

Molecules 2023, 28(16), 5938; https://doi.org/10.3390/molecules28165938 - 08 Aug 2023

Cited by 1 | Viewed by 1069

Abstract

Two types of angiotensin-converting enzyme (ACE) inhibitors, lisinopril and benazepril HCl, were tested in neuroblastoma cells and found to upregulate low-density lipoprotein-receptor-related protein 1B (LRP1B) and 14-3-3 protein zeta/delta. Additionally, benazepril HCl was found to increase the expression of calreticulin. The upregulation of [...] Read more.

Two types of angiotensin-converting enzyme (ACE) inhibitors, lisinopril and benazepril HCl, were tested in neuroblastoma cells and found to upregulate low-density lipoprotein-receptor-related protein 1B (LRP1B) and 14-3-3 protein zeta/delta. Additionally, benazepril HCl was found to increase the expression of calreticulin. The upregulation of these proteins by ACE inhibitors may contribute to the amelioration of cognitive deficits in Alzheimer’s disease/dementia, as well as the clinically observed deceleration of functional decline in Alzheimer’s patients. This discovery suggests that the supplementation of ACE inhibitors may promote neuronal cell survival independently of their antihypertensive effect. Overall, these findings indicate that ACE inhibitors may be a promising avenue for developing effective treatments for Alzheimer’s disease. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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12 pages, 540 KiB

Open AccessArticle

A Study of the Relationship between Phthalate Exposure and the Occurrence of Adult Asthma in Taiwan

by Tsai-Hui Duh, Chih-Jen Yang, Chien-Hung Lee and Ying-Chin Ko

Molecules 2023, 28(13), 5230; https://doi.org/10.3390/molecules28135230 - 05 Jul 2023

Cited by 1 | Viewed by 815

Abstract

Although phthalate esters contribute to airway remodeling by increasing bronchial cells’ migration and proliferation, the relationship between human exposure to phthalates and asthma is not understood. We measured phthalate exposure in the human body and evaluated its effect on asthma. Asthma (n [...] Read more.

Although phthalate esters contribute to airway remodeling by increasing bronchial cells’ migration and proliferation, the relationship between human exposure to phthalates and asthma is not understood. We measured phthalate exposure in the human body and evaluated its effect on asthma. Asthma (n = 123) and asthma-free (n = 139) participants were, respectively, recruited from an asthma clinic and the community in Taiwan. The urine levels of six phthalate metabolites were determined by liquid chromatography tandem mass spectrometry. Compared with the controls, male asthma patients had higher means of mono-(2-ethylhexyl) phthalate (MEHP) (116.3 nmol/g), monobutyl phthalate (MBP) (850.3 nmol/g) and monoethyl phthalate (MEP) (965.8 nmol/g), and female patients had greater MBP (2902.4 nmol/g). Each 10-fold increase in the level of these phthalate metabolites was correspondingly associated with a 5.0-, 5.8-, 4.2- and 5.3-fold risk of contracting asthma. Male asthma patients were identified to have a higher proportion of MEHP exposure (32.5%) than the controls (25.3%). In asthma patients, an increase in urine MEHP levels and the total phthalate metabolite concentration were notably linked to increased risks of emergency room visits and being hospitalized. For the occurrence and acute clinical events of adult asthma, phthalate exposures and MEHP retention may contribute to higher risks of contracting this respiratory disorder. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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10 pages, 1433 KiB

Open AccessFeature PaperArticle

Investigation of New Psychoactive Substances (NPS), Other Illicit Drugs, and Drug-Related Compounds in a Taiwanese Wastewater Sample Using High-Resolution Mass-Spectrometry-Based Targeted and Suspect Screening

by Yuan-Chih Chen, Jen-Yi Hsu, Chih-Wei Chang, Pin-Yu Chen, Yung-Chieh Lin, I-Lin Hsu, Chiau-Jun Chu, Yen-Ping Lin and Pao-Chi Liao

Molecules 2023, 28(13), 5040; https://doi.org/10.3390/molecules28135040 - 28 Jun 2023

Cited by 1 | Viewed by 1403

Abstract

The proliferation of new psychoactive substances (NPSs) in recent years has posed a significant challenge to public health. Traditional monitoring methods have proven insufficient in tracking these constantly evolving substances, leading to the development of alternative approaches such as wastewater-based epidemiology (WBE). The [...] Read more.

The proliferation of new psychoactive substances (NPSs) in recent years has posed a significant challenge to public health. Traditional monitoring methods have proven insufficient in tracking these constantly evolving substances, leading to the development of alternative approaches such as wastewater-based epidemiology (WBE). The present study aims to utilize high-resolution mass spectrometry (HRMS)-based targeted and suspect screening to profile NPS, other illicit drugs, and drug-related compounds in a Taiwanese wastewater sample. For the targeted analysis, 8 out 18 standards of illicit drugs have been identified. The suspect screening approach based on approximately 3600 substances in the SWGDRUG library can further identify 92 compounds, including opiate analgesics, synthetic cathinones, phenylalkylamines derivatives, phenethylamine derivatives, tryptamine derivatives, steroids, and ephedrine-related compounds. Additionally, the presence of 5-methoxy-2-aminoindane (MEAI) in the wastewater indicates that drug dealers have recently sold this potential NPS to evade drug regulations. This study firstly reports the HRMS-based comprehensive profile of NPS, other illicit drugs, and drug-related compounds in Taiwan, which could be applied as biomarkers for estimating the consumption of drugs. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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10 pages, 1537 KiB

Open AccessArticle

Assisted Reductive Amination for Quantitation of Tryptophan, 5-Hydroxytryptophan, and Serotonin by Ultraperformance Liquid Chromatography Coupled with Tandem Mass Spectrometry

by Shih-Shin Liang, Po-Tsun Shen, Yu-Qing Liang, Yi-Wen Ke, Chieh-Wen Cheng and Yi-Reng Lin

Molecules 2023, 28(12), 4580; https://doi.org/10.3390/molecules28124580 - 06 Jun 2023

Viewed by 1490

Abstract

Herein, we used isotopic formaldehyde and sodium cyanoborohydride via reductive amination to label two methyl groups on primary amine to arrange the standards (h₂-formaldehyde-modified) and internal standards (ISs, d₂-formaldehyde-modified) of tryptophan and its metabolites, such as serotonin (5-hydroxytryptamine) [...] Read more.

Herein, we used isotopic formaldehyde and sodium cyanoborohydride via reductive amination to label two methyl groups on primary amine to arrange the standards (h₂-formaldehyde-modified) and internal standards (ISs, d₂-formaldehyde-modified) of tryptophan and its metabolites, such as serotonin (5-hydroxytryptamine) and 5-hydroxytryptophan. These derivatized reactions with a high yield are very satisfactory for manufacturing standards and ISs. This strategy will generate one or two methyl groups on amine to create different mass unit shifts with 14 vs. 16 or 28 vs. 32 in individual compounds for biomolecules with amine groups. In other words, multiples of two mass units shift are created using this derivatized method with isotopic formaldehyde. Serotonin, 5-hydroxytryptophan, and tryptophan were used as examples to demonstrate isotopic formaldehyde-generating standards and ISs. h₂-formaldehyde-modified serotonin, 5-hydroxytryptophan, and tryptophan are standards to construct calibration curves, and d₂-formaldehyde-modified analogs such as ISs spike into samples to normalize the signal of each detection. We utilized multiple reaction monitoring modes and triple quadrupole mass spectrometry to demonstrate the derivatized method suitable for these three nervous biomolecules. The derivatized method demonstrated a linearity range of the coefficient of determinations between 0.9938 to 0.9969. The limits of detection and quantification ranged from 1.39 to 15.36 ng/mL. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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17 pages, 2035 KiB

Open AccessArticle

Proteomic Signature of Extracellular Vesicles Associated with Colorectal Cancer

by Natalia Soloveva, Svetlana Novikova, Tatiana Farafonova, Olga Tikhonova and Victor Zgoda

Molecules 2023, 28(10), 4227; https://doi.org/10.3390/molecules28104227 - 22 May 2023

Cited by 1 | Viewed by 1972

Abstract

The proteins of extracellular vesicles (EVs) provide proteomic signatures that reflect molecular features of EV-producing cells, including cancer cells. Detection of cancer cell EV proteins is of great interest due to the development of novel predictive diagnostic approaches. Using targeted mass spectrometry with [...] Read more.

The proteins of extracellular vesicles (EVs) provide proteomic signatures that reflect molecular features of EV-producing cells, including cancer cells. Detection of cancer cell EV proteins is of great interest due to the development of novel predictive diagnostic approaches. Using targeted mass spectrometry with stable-isotope-labeled peptide standards (SIS), we measured in this study the levels of 34 EV-associated proteins in vesicles and whole lysate derived from the colorectal cancer (CRC) cell lines Caco-2, HT29 and HCT116. We also evaluated the abundance of 13 EV-associated proteins (FN1, TLN1, ITGB3, HSPA8, TUBA4A, CD9, CD63, HSPG2, ITGB1, GNAI2, TSG101, PACSIN2, and CDC42) in EVs isolated from blood plasma samples from 11 CRC patients and 20 healthy volunteers. Downregulation of TLN1, ITGB3, and TUBA4A with simultaneous upregulation of HSPG2 protein were observed in cancer samples compared to healthy controls. The proteomic cargo of the EVs associated with CRC represents a promising source of potential prognostic markers. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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19 pages, 10590 KiB

Open AccessFeature PaperArticle

Identification of Protein Quality Markers in Toad Venom from Bufo gargarizans

by Meiyun Yang, Weiwei Huan, Guobing Zhang, Jie Li, Fengyan Xia, Rabia Durrani, Wei Zhao, Jidong Lu, Xinmeng Peng and Fei Gao

Molecules 2023, 28(8), 3628; https://doi.org/10.3390/molecules28083628 - 21 Apr 2023

Cited by 2 | Viewed by 1762

Abstract

Toad venom is a traditional Chinese medicine with high medicinal value. The existing quality evaluation standards of toad venom have obvious limitations because of the lack of research on proteins. Thus, it is necessary to screen suitable quality markers and establish appropriate quality [...] Read more.

Toad venom is a traditional Chinese medicine with high medicinal value. The existing quality evaluation standards of toad venom have obvious limitations because of the lack of research on proteins. Thus, it is necessary to screen suitable quality markers and establish appropriate quality evaluation methods for toad venom proteins to guarantee their safety and efficacy in clinical applications. SDS-PAGE, HPLC, and cytotoxicity assays were used to analyze differences in protein components of toad venom from different areas. Functional proteins were screened as potential quality markers by proteomic and bioinformatic analyses. The protein components and small molecular components of toad venom were not correlated in content. Additionally, the protein component had strong cytotoxicity. Proteomics analysis showed that 13 antimicrobial proteins, four anti-inflammatory and analgesic proteins, and 20 antitumor proteins were differentially expressed extracellular proteins. A candidate list of functional proteins was coded as potential quality markers. Moreover, Lysozyme C-1, which has antimicrobial activity, and Neuropeptide B (NPB), which has anti-inflammatory and analgesic activity, were identified as potential quality markers for toad venom proteins. Quality markers can be used as the basis of quality studies of toad venom proteins and help to construct and improve safe, scientific, and comprehensive quality evaluation methods. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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13 pages, 1926 KiB

Open AccessArticle

Untargeted Metabolomics Using UHPLC-HRMS Reveals Metabolic Changes of Fresh-Cut Potato during Browning Process

by Baohong Li, Yingjie Fu, Hui Xi, Shan Liu, Wuduo Zhao, Peng Li, Wu Fan, Dingzhong Wang and Shihao Sun

Molecules 2023, 28(8), 3375; https://doi.org/10.3390/molecules28083375 - 11 Apr 2023

Cited by 3 | Viewed by 1988

Abstract

Surface browning plays a major role in the quality loss of fresh-cut potatoes. Untargeted metabolomics were used to understand the metabolic changes of fresh-cut potato during the browning process. Their metabolites were profiled by ultra-high performance liquid chromatography coupled with high resolution mass [...] Read more.

Surface browning plays a major role in the quality loss of fresh-cut potatoes. Untargeted metabolomics were used to understand the metabolic changes of fresh-cut potato during the browning process. Their metabolites were profiled by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS). Data processing and metabolite annotation were completed by Compound Discoverer 3.3 software. Statistical analysis was applied to screen the key metabolites correlating with browning process. Fifteen key metabolites responsible for the browning process were putatively identified. Moreover, after analysis of the metabolic causes of glutamic acid, linolenic acid, glutathione, adenine, 12-OPDA and AMP, we found that the browning process of fresh-cut potatoes was related to the structural dissociation of the membrane, oxidation and reduction reaction and energy shortage. This work provides a reference for further investigation into the mechanism of browning in fresh-cut products. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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15 pages, 2458 KiB

Open AccessArticle

Discovering Hair Biomarkers of Alzheimer’s Disease Using High Resolution Mass Spectrometry-Based Untargeted Metabolomics

by Yu-Hsiang Su, Chih-Wei Chang, Jen-Yi Hsu, Shih-Wen Li, Pi-Shan Sung, Ru-Hsueh Wang, Chih-Hsing Wu and Pao-Chi Liao

Molecules 2023, 28(5), 2166; https://doi.org/10.3390/molecules28052166 - 25 Feb 2023

Cited by 1 | Viewed by 2097

Abstract

Hair may be a potential biospecimen to discover biomarkers for Alzheimer’s disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted [...] Read more.

Hair may be a potential biospecimen to discover biomarkers for Alzheimer’s disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted metabolomics approach. A total of 24 patients with AD and 24 age- and sex-matched cognitively healthy controls were recruited. The hair samples were collected 0.1-cm away from the scalp and further cut into 3-cm segments. Hair metabolites were extracted by ultrasonication with methanol/phosphate-buffered saline 50/50 (v/v) for 4 h. A total of 25 discriminatory chemicals in hair between the patients with AD and controls were discovered and identified. The AUC value achieved 0.85 (95% CI: 0.72~0.97) in patients with very mild AD compared to healthy controls using a composite panel of the 9 biomarker candidates, indicating high potential for the initiation or promotion phase of AD dementia in the early stage. A metabolic panel combined with the nine metabolites may be used as biomarkers for the early detection of AD. The hair metabolome can be used to reveal metabolic perturbations for biomarker discovery. Investigating perturbations of the metabolites will offer insight into the pathogenesis of AD. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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Review

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22 pages, 588 KiB

Open AccessReview

Experiences and Perspectives of GC-MS Application for the Search of Low Molecular Weight Discriminants of Schizophrenia

by Natalia Porozova, Elena Danilova, Igor Senshinov, Andreas Tsakalof and Alexander Nosyrev

Molecules 2023, 28(1), 324; https://doi.org/10.3390/molecules28010324 - 31 Dec 2022

Viewed by 1606

Abstract

Schizophrenia is one of the most severe chronic mental disorders that is currently diagnosed and categorized through subjective clinical assessment of complex symptoms. At present, there is a recognized need for an objective, unbiased clinical test for schizophrenia diagnosis at an early stage [...] Read more.

Schizophrenia is one of the most severe chronic mental disorders that is currently diagnosed and categorized through subjective clinical assessment of complex symptoms. At present, there is a recognized need for an objective, unbiased clinical test for schizophrenia diagnosis at an early stage and categorization of the disease. This can be achieved by assaying low-molecular-weight biomarkers of the disease. Here we give an overview of previously conducted research on the discovery of biomarkers of schizophrenia and focus on the studies implemented with the use of GC-MS and the least invasiveness of biological samples acquisition. The presented data demonstrate that GC-MS is a powerful instrumental platform for investigating dysregulated biochemical pathways implicated in schizophrenia pathogenesis. With this platform, different research groups suggested a number of low molecular weight biomarkers of schizophrenia. However, we recognize an inconsistency between the biomarkers or biomarkers patterns revealed by different groups even in the same matrix. Moreover, despite the importance of the problem, the number of relevant studies is limited. The intensification of the research, as well as the harmonization of the analytical procedures to overcome the observed inconsistencies, can be indicated as future directions in the schizophrenia bio-markers quest. Full article

(This article belongs to the Special Issue Mass Spectrometry in Biomarkers Discovery)

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