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Metabolites Sep 2021Lung cancer continues to be a significant burden worldwide and remains the leading cause of cancer-associated mortality. Two considerable challenges posed by this... (Review)
Review
Lung cancer continues to be a significant burden worldwide and remains the leading cause of cancer-associated mortality. Two considerable challenges posed by this disease are the diagnosis of 61% of patients in advanced stages and the reduced five-year survival rate of around 4%. Noninvasively collected samples are gaining significant interest as new areas of knowledge are being sought and opened up. Metabolomics is one of these growing areas. In recent years, the use of metabolomics as a resource for the study of lung cancer has been growing. We conducted a systematic review of the literature from the past 10 years in order to identify some metabolites associated with lung cancer. More than 150 metabolites have been associated with lung cancer-altered metabolism. These were detected in different biological samples by different metabolomic analytical platforms. Some of the published results have been consistent, showing the presence/alteration of specific metabolites. However, there is a clear variability due to lack of a full clinical characterization of patients or standardized patients selection. In addition, few published studies have focused on the added value of the metabolomic profile as a means of predicting treatment response for lung cancer. This review reinforces the need for consistent and systematized studies, which will help make it possible to identify metabolic biomarkers and metabolic pathways responsible for the mechanisms that promote tumor progression, relapse and eventually resistance to therapy.
PubMed: 34564447
DOI: 10.3390/metabo11090630 -
Journal of Translational Medicine May 2020Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) is a complex illness that has an unknown aetiology. It has been... (Review)
Review
BACKGROUND
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) is a complex illness that has an unknown aetiology. It has been proposed that metabolomics may contribute to the illness pathogenesis of CFS/ME/SEID. In metabolomics, the systematic identification of measurable changes in small molecule metabolite products have been identified in cases of both monogenic and heterogenic diseases. Therefore, the aim of this systematic review was to evaluate if there is any evidence of metabolomics contributing to the pathogenesis of CFS/ME/SEID.
METHODS
PubMed, Scopus, EBSCOHost (Medline) and EMBASE were searched using medical subject headings terms for Chronic Fatigue Syndrome, metabolomics and metabolome to source papers published from 1994 to 2020. Inclusion and exclusion criteria were used to identify studies reporting on metabolites measured in blood and urine samples from CFS/ME/SEID patients compared with healthy controls. The Joanna Briggs Institute Checklist was used to complete a quality assessment for all the studies included in this review.
RESULTS
11 observational case control studies met the inclusion criteria for this review. The primary outcome of metabolite measurement in blood samples of CFS/ME/SEID patients was reported in ten studies. The secondary outcome of urine metabolites was measured in three of the included studies. No studies were excluded from this review based on a low-quality assessment score, however there was inconsistency in the scientific research design of the included studies. Metabolites associated with the amino acid pathway were the most commonly impaired with significant results in seven out of the 10 studies. However, no specific metabolite was consistently impaired across all of the studies. Urine metabolite results were also inconsistent.
CONCLUSION
The findings of this systematic review reports that a lack of consistency with scientific research design provides little evidence for metabolomics to be clearly defined as a contributing factor to the pathogenesis of CFS/ME/SEID. Further research using the same CFS/ME/SEID diagnostic criteria, metabolite analysis method and control of the confounding factors that influence metabolite levels are required.
Topics: Case-Control Studies; Fatigue Syndrome, Chronic; Humans; Metabolomics
PubMed: 32404171
DOI: 10.1186/s12967-020-02356-2 -
Journal of Clinical Medicine May 2020The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but... (Review)
Review
The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.
PubMed: 32403255
DOI: 10.3390/jcm9051420 -
Expert Reviews in Molecular Medicine Apr 2022Preterm birth (PTB) is one of the leading causes of deaths in infants under the age of five. Known risk factors of PTB include genetic factors, lifestyle choices or... (Review)
Review
Preterm birth (PTB) is one of the leading causes of deaths in infants under the age of five. Known risk factors of PTB include genetic factors, lifestyle choices or infection. Identification of omic biomarkers associated with PTB could aid clinical management of women at high risk of early labour and thereby reduce neonatal morbidity. This systematic literature review aimed to identify and summarise maternal omic and multi-omic (genomics, transcriptomics, proteomics and metabolites) biomarker studies of PTB. Original research articles were retrieved from three databases: PubMed, Web of Science and Science Direct, using specified search terms for each omic discipline. PTB studies investigating genomics, transcriptomics, proteomics or metabolomics biomarkers prior to onset of labour were included. Data were collected and reviewed independently. Pathway analyses were completed on the biomarkers from non-targeted omic studies using Reactome pathway analysis tool. A total of 149 omic studies were identified; most of the literature investigated proteomic biomarkers. Pathway analysis identified several cellular processes associated with the omic biomarkers reported in the literature. Study heterogeneity was observed across the research articles, including the use of different gestation cut-offs to define PTB. Infection/inflammatory biomarkers were identified across majority of papers using a range of targeted and non-targeted approaches.
PubMed: 35379367
DOI: 10.1017/erm.2022.13 -
Investigative Ophthalmology & Visual... Aug 2021Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with...
PURPOSE
Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with diabetes still develop DR despite appropriate glycemic and blood pressure control, highlighting the pressing need to identify useful biomarkers for risk stratification. The purpose of this review is to systematically summarize potential metabolic biomarkers and pathways of DR, which could facilitate developing an understanding of the disease mechanisms, as well as new therapeutic measures.
METHODS
We searched PubMed and Web of Science for relevant metabolomics studies on humans published before September 30, 2020. Information regarding authors, title, publication date, study subjects, analytical platforms, methods of statistical analysis, biological samples, directions of change of potential metabolic biomarkers, and predictive values of metabolic biomarker panels was extracted, and the quality of the studies was assessed. Pathway analysis, including enrichment analysis and topology analysis, was derived from integrating differential metabolites using MetaboAnalyst 3.0, based on the Kyoto Encyclopedia of Genes and Genomes and Human Metabolome Database.
RESULTS
We found nine studies focused on the identification of potential biomarkers. Repeatedly identified metabolites including l-glutamine, l-lactic acid, pyruvic acid, acetic acid, l-glutamic acid, d-glucose, l-alanine, l-threonine, citrulline, l-lysine, and succinic acid were found to be potential biomarkers of DR. It was observed that l-glutamine and citrulline changed in all biological samples. Dysregulation of metabolic pathways involved amino acid and energy metabolism.
CONCLUSIONS
This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.
Topics: Biomarkers; Diabetic Retinopathy; Humans; Metabolic Networks and Pathways; Metabolome; Metabolomics
PubMed: 34347011
DOI: 10.1167/iovs.62.10.4 -
Journal of Cancer 2020Breast cancer (BC) remains the most frequent type of cancer in females worldwide. However, the pathogenesis of BC is still under the cloud, along with the huge challenge... (Review)
Review
Breast cancer (BC) remains the most frequent type of cancer in females worldwide. However, the pathogenesis of BC is still under the cloud, along with the huge challenge of early diagnosis, which is widely acknowledged as the key to a successful therapy. Metabolomics, a newborn innovative technique in recent years, has demonstrated great potential in cancer-related researches. The aim of this review is to look back on clinical and cellular metabolomic studies in the diagnosis of BC over the past decade, and provide a systematic summary of metabolic biomarkers and pathways related to BC diagnosis.
PubMed: 32201524
DOI: 10.7150/jca.37604 -
Pharmaceuticals (Basel, Switzerland) Oct 2021Pharmacometabolomics (PMx) studies aim to predict individual differences in treatment response and in the development of adverse effects associated with specific drug... (Review)
Review
Pharmacometabolomics (PMx) studies aim to predict individual differences in treatment response and in the development of adverse effects associated with specific drug treatments. Overall, these studies inform us about how individuals will respond to a drug treatment based on their metabolic profiles obtained before, during, or after the therapeutic intervention. In the era of precision medicine, metabolic profiles hold great potential to guide patient selection and stratification in clinical trials, with a focus on improving drug efficacy and safety. Metabolomics is closely related to the phenotype as alterations in metabolism reflect changes in the preceding cascade of genomics, transcriptomics, and proteomics changes, thus providing a significant advance over other omics approaches. Nuclear Magnetic Resonance (NMR) is one of the most widely used analytical platforms in metabolomics studies. In fact, since the introduction of PMx studies in 2006, the number of NMR-based PMx studies has been continuously growing and has provided novel insights into the specific metabolic changes associated with different mechanisms of action and/or toxic effects. This review presents an up-to-date summary of NMR-based PMx studies performed over the last 10 years. Our main objective is to discuss the experimental approaches used for the characterization of the metabolic changes associated with specific therapeutic interventions, the most relevant results obtained so far, and some of the remaining challenges in this area.
PubMed: 34681239
DOI: 10.3390/ph14101015 -
Developmental Neuroscience 2022Early life stress is commonly experienced by infants, especially preterm infants, and may impact their neurodevelopmental outcomes in their early and later lives.... (Review)
Review
Early life stress is commonly experienced by infants, especially preterm infants, and may impact their neurodevelopmental outcomes in their early and later lives. Mitochondrial function/dysfunction may play an important role underlying the linkage of prenatal and postnatal stress and neurodevelopmental outcomes in infants. This review aimed to provide insights on the relationship between early life stress and neurodevelopment and the mechanisms of mitochondrial function/dysfunction that contribute to the neuropathology of stress. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to develop this systematic review. PubMed, Scopus, PsycINFO, and Biosis databases were searched for primary research articles published between 2010 and 2021 that examined the relationships among mitochondrial function/dysfunction, infant stress, and neurodevelopment. Thirty studies were identified. There is evidence to support that mitochondrial function/dysfunction mediates the relationship between prenatal and postnatal stress and neurodevelopmental outcomes in infants. Maternal transgenerational transmission of mitochondrial bioenergetic patterns influenced prenatal stress induced neurodevelopmental outcomes and behavioral changes in infants. Multiple functionally relevant mitochondrial proteins, genes, and polymorphisms were associated with stress exposure. This is the first review of the role that mitochondrial function/dysfunction plays in the association between stress and neurodevelopmental outcomes in full-term and preterm infants. Although multiple limitations were found based on the lack of data on the influence of biological sex, and due to invasive sampling, and lack of longitudinal data, many genes and proteins associated with mitochondrial function/dysfunction were found to influence neurodevelopmental outcomes in the early life of infants.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Infant, Premature; Mitochondria; Stress, Physiological; Neurodevelopmental Disorders
PubMed: 35995037
DOI: 10.1159/000526491 -
Sleep and Biological Rhythms Jul 2023Obstructive Sleep Apnea (OSA) corresponds to episodes of complete or partial upper airway obstruction during sleep. The gold standard for diagnosing OSA is... (Review)
Review
Obstructive Sleep Apnea (OSA) corresponds to episodes of complete or partial upper airway obstruction during sleep. The gold standard for diagnosing OSA is polysomnography; however, metabolomics is an innovative and highly sensitive method that seeks to identify and quantify small molecules in biological systems. Identify the metabolites most frequently associated with obstructive sleep apnea in adults. The search for articles was conducted between October 2020 and August 2021, in electronic databases, such as MEDLINE/PubMed, Scielo, Embase, and Cochrane, through the combination of descriptors: obstructive sleep apnea, metabolomic, adult. This systematic review included all cross-sectional studies published, including human patients aged 18 years or older, of both genders who underwent type I or II polysomnography and metabolomics study. The search strategy selected 3697 surveys, and 4 of them were selected to be a part of this systematic review. Based on the analyzed surveys, it was found that all of them were able to diagnose OSA, reaching a sensitivity of 75-97%, and specificity that ranged from 72 to 100%; besides differentiating patients with OSA (severe, moderate, and mild) from simple snorers with a mean sensitivity of 77.2% and specificity of 66.25%. These findings suggest that, in addition to being used as a screening and diagnostic strategy for OSA, metabolomics has the potential to be used for severity stratification and to monitor the disease's progression.
PubMed: 38469078
DOI: 10.1007/s41105-023-00445-5 -
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