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International Journal of Molecular... May 2023Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus of biomedical research for decades. To this... (Review)
Review
Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well-accepted biomarkers in kidney disease. With their known blind spot in the early stages of kidney impairment and their diagnostic limitations, there is a need for better and more specific biomarkers. With the rise in large-scale analyses of the thousands of peptides in serum or urine samples using mass spectrometry techniques, hopes for biomarker development are high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and the identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review that strictly follows the PRISMA guidelines, we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. The Web of Science database (all databases) was searched on 17 October 2022, using the search terms "marker *" OR biomarker * AND "renal disease" OR "kidney disease" AND "proteome *" OR "peptid *" AND "urin *". English, full-text, original articles on humans published within the last 5 years were included, which had been cited at least five times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA, and studies on exosomal vesicles were excluded, focusing on urinary peptide biomarkers. The described search led to the identification of 3668 articles and the application of inclusion and exclusion criteria, as well as abstract and consecutive full-text analyses of three independent authors to reach a final number of 62 studies for this manuscript. The 62 manuscripts encompassed eight established single peptide biomarkers and several proteomic classifiers, including CKD273 and IgAN237. This review provides a summary of the recent evidence on single peptide urinary biomarkers in CKD, while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies, hopefully resulting in the routine clinical applicability of new biomarkers.
Topics: Humans; Proteomics; Renal Insufficiency, Chronic; Kidney; Peptides; Biomarkers
PubMed: 37298105
DOI: 10.3390/ijms24119156 -
Chemical Research in Toxicology Mar 2023The introduction of synthetic nicotine by the tobacco industry, also promoted as tobacco-free nicotine, presented new challenges for analytical chemists working in... (Review)
Review
The introduction of synthetic nicotine by the tobacco industry, also promoted as tobacco-free nicotine, presented new challenges for analytical chemists working in tobacco regulatory science to develop and optimize new methods to assess new nicotine parameters, namely enantiomer ratio and source. We conducted a systematic literature review of the available analytical methods to detect the nicotine enantiomer ratio and the source of nicotine using PubMed and Web of Science databases. Methods to detect nicotine enantiomers included polarimetry, nuclear magnetic resonance, and gas and liquid chromatography. We also covered methods developed to detect the source of nicotine either indirectly via determining the nicotine enantiomer ratio or the detection of tobacco-specific impurities or directly using the isotope ratio enrichment analysis by nuclear magnetic resonance (site-specific natural isotope fractionation and site-specific peak intensity ratio) or accelerated mass spectrometry. This review presents an accessible summary of all these analytical methods.
Topics: Nicotine; Mass Spectrometry; Chromatography, Liquid
PubMed: 36897818
DOI: 10.1021/acs.chemrestox.2c00310 -
MedRxiv : the Preprint Server For... Feb 2023Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to...
AIMS
Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development.
METHODS
This systematic review was registered with Open Science Framework (DOI 10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria.
RESULTS
A total of 13 studies met our inclusion criteria, resulting in the identification of 251 unique proteins, with 27 (11%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found a subset of 3 proteins (C3, KNG1 & CFAH), 6 proteins (C3, C4A, APOA4, C4B, A2AP & BTD) and 7 proteins (C3, CLUS, APOA4, C6, A2AP, C1R & CFAI) have consistent regulation between multiple studies in samples from individuals at pre-seroconversion, post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development.
CONCLUSIONS
Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.
PubMed: 36865103
DOI: 10.1101/2023.02.21.23286132 -
Life (Basel, Switzerland) Jan 2023Mass spectrometry imaging is a sensitive method for detecting molecules in tissues in their native form. Lipids mainly act as energy stores and membrane constituents,... (Review)
Review
Mass spectrometry imaging is a sensitive method for detecting molecules in tissues in their native form. Lipids mainly act as energy stores and membrane constituents, but they also play a role in lipid signaling. Previous studies have suggested an important role of lipids in implantation; therefore, our aim was to investigate the lipid changes during this period based on the available literature. The systematic literature search was performed on Ovid MEDLINE, Cochrane Library, Embase, and LILACS. We included studies about lipid changes in the early embryonal stage of healthy mammalian development published as mass spectrometry imaging. The search retrieved 917 articles without duplicates, and five articles were included in the narrative synthesis of the results. Two articles found a different spatial distribution of lipids in the early bovine embryo and receptive uterus. Three articles investigated lipids in mice in the peri-implantation period and found a different spatial distribution of several glycerophospholipids in both embryonic and maternal tissues. Although only five studies from three different research groups were included in this systematic review, it is clear that the spatial distribution of lipids is diverse in different tissues and their distribution varies from day to day. This may be a key factor in successful implantation, but further studies are needed to elucidate the exact mechanism.
PubMed: 36676119
DOI: 10.3390/life13010169 -
Cureus Jan 2023Drug-facilitated sexual assault (DFSA) is a significant crime that is increasing in incidence. The employment of volatile substances such as chloroform and aromatic... (Review)
Review
Drug-facilitated sexual assault (DFSA) is a significant crime that is increasing in incidence. The employment of volatile substances such as chloroform and aromatic petroleum hydrocarbons in DFSAs is quite an unusual choice. The objective of this review is to explore the use of volatile substances in DFSAs. Using the PubMed database, a systematic review of the literature was conducted. Thereafter, citation searching was carried out within the included studies from the primary search. A total of five studies were eligible for inclusion. Chloroform was the drug used in the DFSA in three of the included studies, and aromatic hydrocarbons in the remaining two. Two of the offenders who employed chloroform possessed a unique way to access the drug: their degrees. The evidence found in the DFSA cases included a chloroform-scented scarf and a solvent-immersed cloth. Headspace gas chromatography-mass spectrometry, liquid chromatography-electrospray coupled tandem mass spectrometry, toxicology assays of blood and urine, and solvent or hydrocarbon gas chromatography flame-ionization detection followed by gas chromatography-mass spectrometry were among the investigations performed to detect the volatile substances. The implementation of stricter regulations on chloroform for employees in chemical industries and laboratories is recommended. In cases where the autopsy is unclear and there are conspicuous facial and airway injuries, it is prudent to collect an early sample for volatile substance analysis.
PubMed: 36628398
DOI: 10.7759/cureus.33430 -
Frontiers in Endocrinology 2022Primary aldosteronism (PA) is currently considered the most common cause of secondary and endocrine hypertension. Liquid chromatography-tandem mass spectrometry... (Meta-Analysis)
Meta-Analysis
Clinical diagnostic value of liquid chromatography-tandem mass spectrometry method for primary aldosteronism in patients with hypertension: A systematic review and meta-analysis.
BACKGROUND
Primary aldosteronism (PA) is currently considered the most common cause of secondary and endocrine hypertension. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a new detection technique has been gradually applied in the diagnosis of PA. However, the diagnostic value of LC-MS/MS methods for PA has not been systematically clinically validated. The aim was to access the diagnostic accuracy, sensitivity, and specificity of LC-MS/MS methods as screening tools in PA.
MATERIALS AND METHODS
A literature search of PubMed, Embase, Medline, Web of Science, Scopus, Science Direct, and Chinese databases was carried out to June 2022 with no language restriction. Data on sensitivity and specificity and other evaluation indicators were extracted and pooled with STATA and Meta-disc software. Heterogeneity was evaluated and meta-regression and subgroup analysis was performed to elucidate sources of heterogeneity.
RESULTS
12 studies of the diagnostic test were suitable and included in the meta-analysis. Pooled sensitivity, specificity, and diagnostic odds ratio were 0.89 (95% CI: 0.83-0.93), 0.87 (95% CI: 0.82-0.91), and 55 (95% CI: 28-110), respectively. Subgroup analysis assessed the diagnostic power of LC-MS/MS based on the type of detection index. ARR and PAC based on LC-MS/MS methods have the higher diagnostic value compared with other indices, diagnostic odds ratios were 121.65 (95% CI: 36.28-407.98) and 49.85 (95% CI: 24.87-99.93). There was considerable heterogeneity among studies.
CONCLUSION
LC-MS/MS methods had higher accuracy and reliability in the diagnosis of primary aldosteronism. LC-MS/MS-based ARR and PAC can be further promoted and applied in the diagnosis of primary aldosteronism.
Topics: Humans; Chromatography, Liquid; Reproducibility of Results; Tandem Mass Spectrometry; Hypertension; Hyperaldosteronism
PubMed: 36465649
DOI: 10.3389/fendo.2022.1032070 -
Life (Basel, Switzerland) Sep 2022Alcohol consumption during pregnancy, even at low doses, may damage the fetus. Pregnant women tend to underreport their alcohol consumption generating the need for... (Review)
Review
BACKGROUND
Alcohol consumption during pregnancy, even at low doses, may damage the fetus. Pregnant women tend to underreport their alcohol consumption generating the need for sensitive and specific biomarkers, among which PEth has emerged due to its high specificity and possibility to be measured in both maternal and neonatal blood. The aim of this study is to systematically review the latest 20 years of literature for depicting the state of the art, the limitations, and the prospects of PEth for estimating alcohol consumption during pregnancy.
MATERIALS AND METHODS
A systematic search, adhering to PRISMA guidelines, of the latest 20 years of literature through "MeSH" and "free-text" protocols in the databases PubMed, SCOPUS, and Web of Science, with time limits 1 January 2002-1 March 2022, was performed. The inclusion criteria were as follows: PEth used for detecting alcohol consumption during pregnancy, quantified in blood through liquid chromatography coupled to mass spectrometry, and full texts in the English language. Opinion papers, editorials, and narrative reviews were excluded.
RESULTS
Sixteen (16) papers were included in the present review (0.81% of total retrieved records). All the included records were original articles, of which there were seven prospective cohort/longitudinal studies, six cross-sectional studies, two observational-descriptive studies, and one retrospective study. All studies assayed PEth in at least one biological matrix; seven (7) studies quantified PEth in maternal blood, seven studies in newborn blood, and only two studies in both maternal and neonatal blood. In several included papers, PEth proved more sensitive than self-reports for identifying pregnant women with an active alcohol intake with the diagnostic efficiency improving with the increase of the maternal alcohol intake.
CONCLUSIONS
Further studies, performed on wider and well-stratified populations, are needed to drive any definitive conclusion. PEth is a promising marker for monitoring alcohol use in pregnancy; however, at the present time, its use is still limited mainly by the absence of a globally agreed interpretative cut-off, the paucity of data regarding its specificity/sensitivity, and the lack of standardization on the diagnostic efficiency of the different isoforms.
PubMed: 36294962
DOI: 10.3390/life12101528 -
Frontiers in Nutrition 2022Obesity treatment strategies mainly include outpatient lifestyle modification, drugs and bariatric surgery. Voluntary rehabilitative inpatient programs are gaining...
BACKGROUND
Obesity treatment strategies mainly include outpatient lifestyle modification, drugs and bariatric surgery. Voluntary rehabilitative inpatient programs are gaining relevance as potential alternative settings of care that focus on weight loss and prevention of weight regain through a multidisciplinary approach, but their prevalence is still limited due to the high costs.
AIM
Considering the lack of evidence in this area, the objective of this study is to systematically review the currently available literature on non-pharmacological and non-surgical inpatient programs aimed at weight loss, to clarify the efficacy and the characteristics of these interventions.
METHODS
Proper English language articles from 2000 to 2022 were searched on relevant databases. Quality assessment was performed by two different authors using and tools. Adult and pediatric studies were reviewed separately and their characteristics were systematically displayed.
RESULTS
36 articles were included (20 on adults, 16 on children, and adolescents) for a total of 5,510 individuals. The multidisciplinary approach was mainly comprehensive of a low-calorie diet, scheduled physical activity, and psychological support based on behavioral treatment. Educational and cooking sessions were present at a lower rate. Globally, inpatient weight loss programs showed a consistent efficacy in reducing body weight and inducing beneficial effects on quality of life, psychological well-being, eating behavior, physical performance, and fatigue. Follow-up data were scarce, but with a high percentage of patients regaining weight after a short period.
CONCLUSION
Weight loss inpatient rehabilitation is a promising area that has evidence of all-rounded success in the amelioration of several aspects related to obesity. Nevertheless, it appears to be quite inconsistent in preserving these benefits after the intervention. This might slow the innovation process in this area and preclude further investments from national healthcare. Personalized and enriched programs could show greater impact when focusing on the behavioral and educational aspects, which are crucial points, in particular in pediatrics, for setting up a long-lasting lifestyle modification. More studies are therefore necessary to evaluate long-term efficacy based on the different work-up models.
PubMed: 36245519
DOI: 10.3389/fnut.2022.963709 -
Nutrients Sep 2022Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a... (Review)
Review
Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell’s stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3−V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results.
Topics: Alanine; Biomarkers; Enterocolitis, Necrotizing; Gastrointestinal Microbiome; Histidine; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Perforation; Metabolome; RNA, Ribosomal, 16S
PubMed: 36145235
DOI: 10.3390/nu14183859 -
Metabolites Sep 2022The analysis of volatile organic compounds (VOCs) can provide important clinical information (entirely non-invasively); however, the exact extent to which VOCs from... (Review)
Review
The analysis of volatile organic compounds (VOCs) can provide important clinical information (entirely non-invasively); however, the exact extent to which VOCs from human skin can be signatures of health and disease is unknown. This systematic review summarises the published literature concerning the methodology, application, and volatile profiles of skin VOC studies. An online literature search was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis, to identify human skin VOC studies using untargeted mass spectrometry (MS) methods. The principal outcome was chemically verified VOCs detected from the skin. Each VOC was cross-referenced using the CAS number against the Human Metabolome and KEGG databases to evaluate biological origins. A total of 29 studies identified 822 skin VOCs from 935 participants. Skin VOCs were commonly sampled from the hand ( = 9) or forearm ( = 7) using an absorbent patch ( = 15) with analysis by gas chromatography MS ( = 23). Twenty-two studies profiled the skin VOCs of healthy subjects, demonstrating a volatolome consisting of aldehydes (18%), carboxylic acids (12%), alkanes (12%), fatty alcohols (9%), ketones (7%), benzenes and derivatives (6%), alkenes (2%), and menthane monoterpenoids (2%). Of the VOCs identified, 13% had putative endogenous origins, 46% had tentative exogenous origins, and 40% were metabolites from mixed metabolic pathways. This review has comprehensively profiled the human skin volatolome, demonstrating the presence of a distinct VOC signature of healthy skin, which can be used as a reference for future researchers seeking to unlock the clinical potential of skin volatolomics. As significant proportions of identified VOCs have putative exogenous origins, strategies to minimise their presence through methodological refinements and identifying confounding compounds are discussed.
PubMed: 36144228
DOI: 10.3390/metabo12090824