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Neuroscience and Biobehavioral Reviews Jul 2024H-Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique that can be used to quantify the concentrations of metabolites in the brain in vivo. MRS findings in... (Meta-Analysis)
Meta-Analysis Review
H-Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique that can be used to quantify the concentrations of metabolites in the brain in vivo. MRS findings in the context of autism are inconsistent and conflicting. We performed a systematic review and meta-analysis of MRS studies measuring glutamate and gamma-aminobutyric acid (GABA), as well as brain metabolites involved in energy metabolism (glutamine, creatine), neural and glial integrity (e.g. n-acetyl aspartate (NAA), choline, myo-inositol) and oxidative stress (glutathione) in autism cohorts. Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes. Overall, we find significantly lower concentrations of GABA and NAA in autism, indicative of disruptions to the balance between excitation/inhibition within brain circuits, as well as neural integrity. Further analysis found these alterations are most pronounced in autistic children and in limbic brain regions relevant to autism phenotypes. Additionally, we show how study outcome varies due to demographic and methodological factors , emphasising the importance of conforming with standardised consensus study designs and transparent reporting.
Topics: Humans; Autistic Disorder; Magnetic Resonance Spectroscopy; Brain; gamma-Aminobutyric Acid; Glutamic Acid
PubMed: 38796123
DOI: 10.1016/j.neubiorev.2024.105728 -
Asian Journal of Surgery May 2024The gut microbiome is the entirety of microorganisms and their genomes residing in the gut, characterised by diversity, stability, and resilience. Disrupted gut... (Review)
Review
The gut microbiome is the entirety of microorganisms and their genomes residing in the gut, characterised by diversity, stability, and resilience. Disrupted gut microbiome has been implicated in multiple disease entities. The aim of this paper is to summarise the rapidly evolving contemporary evidence of gut dysbiosis on the development and progression of abdominal aortic aneurysm (AAA), discuss possible mechanisms, and explore potential microbiota-targeted interventions and prognostic markers for AAA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using PubMed, ScienceDirect, Web of Science, Ovid, Embase. Search terms of "microbiome" OR "dysbiosis" OR "microorganism"; AND "aneurysm" OR "dilatation" OR "aorta" were used. Study endpoints included effects of microbiota on AAA formation, effects of specific type of bacteria and its metabolite on AAA formation, and pre- or post-treatment by novel small-molecules/inhibitors. From May to August 2023, a total of twelve animal studies and eight human studies were included. Akkermansia muciniphila, Lactobacillus acidophilus and species from the Bacteroidetes phylum were associated with lower AAA incidence in both animal and human studies, while Proteobacteria phylum, Campylobacter, Fusobacterium and Faecalibacterium prausnitzii were found to be in abundance in the AAA group and were associated with larger aneurysms. The diversity of gut microbiota was inversely correlated with AAA diameter. Three important mechanisms were identified: including trimethylamine N-oxide pathway, butyric acid pathway, and aberrant tryptophan metabolism. With our expanding knowledge of the downstream pathogenic mechanisms of gut dysbiosis, novel therapeutics such as short-chain fatty acids and spermidine, as well as prognostic biomarkers such as TMAO have yielded promising preclinical results. In conclusion, there is strong evidence corroborating the role of gut dysbiosis in the pathogenesis of AAA, wherein its therapeutic and prognostic potential deserves further exploration.
PubMed: 38772822
DOI: 10.1016/j.asjsur.2024.05.058 -
Progress in Neuro-psychopharmacology &... Jul 2024Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics.
METHODS
A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines.
RESULTS
A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10, 95%CI = -16.08 to -8.58 × 10 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5.
CONCLUSIONS
Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.
Topics: Humans; Pregnancy; Anticonvulsants; Female; Pregnancy Complications; Levetiracetam; Lamotrigine; Epilepsy; Oxcarbazepine
PubMed: 38762161
DOI: 10.1016/j.pnpbp.2024.111030 -
Psychoneuroendocrinology Aug 2024Allopregnanolone (ALLO) is a metabolite of progesterone and a neuroactive steroid hormone. As a positive allosteric modulator of gamma-aminobutyric acid (GABA)...
BACKGROUND
Allopregnanolone (ALLO) is a metabolite of progesterone and a neuroactive steroid hormone. As a positive allosteric modulator of gamma-aminobutyric acid (GABA) receptors, ALLO seems to have antidepressant and anxiolytic effects, and was therefore approved as a specific medication for the treatment of postpartum depression in 2019. Despite the growing number of publications investigating ALLO levels, results on the biological and psychological correlates in the peripartum period remain inconsistent, possibly due to methodological challenges regarding measurement. To date, however, there is no systematic review examining the correlates, concentrations, and challenges in measuring ALLO in peripartum women.
METHOD
A systematic literature search of PubMed and PsycINFO was conducted in August 2023. Original research articles that measured ALLO concentrations in peripartum women were included. Reports were excluded if they were not original research, included non-human subjects, did not include peripartum women, did not include ALLO measurement as an outcome, included (pharmacological) interventions, constituted method validations, or used the same cohort as another study.
RESULTS
The literature search yielded 234 articles, and two articles were identified from other sources. After full-text screening, 19 articles (N = 1401) met the inclusion criteria, of which seven focused on biological correlates of ALLO and 12 on mood correlates. Of the latter, six found no association between ALLO and mood, four found a negative association, and two found a positive association. Overall, the results show an increase in ALLO levels during pregnancy and a decrease after birth, with levels then remaining low until six months postpartum. ALLO was most commonly measured in blood plasma and by gas chromatography-mass spectrometry (GC-MS). A significant matrix effect was found for blood serum and a significant method effect for radioimmunoassays (RIAs). A significant effect of time of measurement was found.
CONCLUSION
ALLO measurement shows method and matrix effects. ALLO levels are higher when measured in serum compared to in plasma, and when measured using RIA compared to other methods. Time of measurement, study design, and standardization of measurement also influence the reliability of measurement and the interpretation of results.
Topics: Humans; Pregnanolone; Female; Peripartum Period; Pregnancy; Depression, Postpartum; Adult
PubMed: 38759520
DOI: 10.1016/j.psyneuen.2024.107081 -
Revista de Saude Publica 2024To identify the prevalence of contamination by pesticides and their metabolites in the milk of lactating mothers in Latin America.
OBJECTIVE
To identify the prevalence of contamination by pesticides and their metabolites in the milk of lactating mothers in Latin America.
METHODS
In this systematic review, the PubMed, LILACS, Embase, and Scopus databases were searched up to January 2022 to identify observational studies. The Mendeley software was used to manage these references. The risk of bias assessment was evaluated according to the checklist for prevalence studies and writing design, by the Prisma guidelines.
RESULTS
This study retrieved 1835 references and analyzed 49 studies. 69.38% of the analyzed studies found a 100% prevalence of breast milk contamination by pesticides among their sample. Main pesticides include dichlorodiphenyltrichloroethane (DDT) and its isomers (75.51%), followed by the metabolite dichlorodiphenyldichloroethylene (DDE) (69.38%) and hexachlorocyclohexane (HCH) (46.93%). This study categorized most (65.30%) studies as having a low risk of bias.
CONCLUSIONS
This review shows a high prevalence of pesticide contamination in the breast milk of Latin American women. Further investigations should be carried out to assess contamination levels in breast milk and the possible effects of these substances on maternal and child health.
Topics: Humans; Milk, Human; Female; Latin America; Lactation; Pesticides; Pesticide Residues; Prevalence; DDT; Maternal Exposure
PubMed: 38747867
DOI: 10.11606/s1518-8787.2024058005446 -
Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
International Journal of Molecular... Apr 2024Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body... (Review)
Review
Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body temperature, and immune response. In this review, we highlight the relevance of the different mediators that control adipose tissue activity through a systematic review of the main players present in white and brown adipose tissues. Among them, inflammatory mediators secreted by the adipose tissue, such as classical adipokines and more recent ones, elements of the immune system infiltrated into the adipose tissue (certain cell types and interleukins), as well as the role of intestinal microbiota and derived metabolites, have been reviewed. Furthermore, anti-obesity mediators that promote the activation of beige adipose tissue, e.g., myokines, thyroid hormones, amino acids, and both long and micro RNAs, are exhaustively examined. Finally, we also analyze therapeutic strategies based on those mediators that have been described to date. In conclusion, novel regulators of obesity, such as microRNAs or microbiota, are being characterized and are promising tools to treat obesity in the future.
Topics: Humans; Animals; Obesity; Adipose Tissue; Adipokines; MicroRNAs; Gastrointestinal Microbiome; Adipose Tissue, Brown; Adipose Tissue, White; Inflammation Mediators; Energy Metabolism
PubMed: 38731880
DOI: 10.3390/ijms25094659 -
Heliyon May 2024Magnetic resonance spectroscopy (MRS) is an imaging technique used to measure metabolic changes in the tissue. Due to the lack of evidence, MRS is not a priority in...
BACKGROUND
Magnetic resonance spectroscopy (MRS) is an imaging technique used to measure metabolic changes in the tissue. Due to the lack of evidence, MRS is not a priority in diagnosing neurodegenerative diseases because it is a relatively specialized technique that requires specialized equipment and expertise to perform and interpret. This systematic review aimed to present a comprehensive collection of MRS results in the most common neurodegenerative diseases.
METHODS
A systematic search of four electronic databases (PubMed, Scopus, Web of Science, and ScienceDirect) was conducted for studies published from 2017 to 2022. Articles that provided specific biomarker levels were selected, and studies that assessed the diseases via treatment, featured MRS applying nuclei other than 1H, or compared different animal models were excluded.
RESULTS
A total of 25 articles, plus 3 articles for extra information in the introduction, were included in this review. Six of the most common neurodegenerative diseases, i.e., Alzheimer's and Parkinson's disease, Huntington chorea, ataxia, multiple sclerosis (MS), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) were examined via MRS. The changes and ratios of N-acetylaspartate (NAA) could be seen in all of these disorders, which could lead to early diagnosis. However, there are other biomarkers, such as Cr and Chon, which can give convincing results.
DISCUSSION
This observational study is the first synthesis of the latest evidence proving metabolic changes during neurodegenerative diseases using MRS as a diagnosis method. The findings indicate decreased N-acetylaspartate (NAA) and NAA/Cr ratios in Alzheimer's disease (AD), Parkinson's disease (PD), ataxias, and MS, reflecting neuronal loss or dysfunction. Increased choline and myo-inositol were noted in some studies, suggesting cell membrane turnover and neuroinflammation. Findings were less consistent for other metabolites like glutamate and gamma-aminobutyric acid. However, there were limitations due to the lack of studies on the same volumes of interest (VOIs) and the small number of participants.
PubMed: 38726104
DOI: 10.1016/j.heliyon.2024.e30521 -
Contemporary Clinical Dentistry 2024Urine as a biofluid has been rarely used as a diagnostic fluid in oral diseases. The article aims to systematically review the utility of human urinary carcinogen... (Review)
Review
AIM
Urine as a biofluid has been rarely used as a diagnostic fluid in oral diseases. The article aims to systematically review the utility of human urinary carcinogen metabolites as an approach for obtaining important information about tobacco and cancer.
MATERIALS AND METHODS
The following article reviews the use of urine and its metabolites as biomarkers in various lesions of the oral cavity including oral squamous cell carcinoma and as a screening method in evaluating tobacco and its components. A bibliographic comprehensive search was carried out in the main databases: PUBMED, SciELO, Google Scholar, VHL, and LILACS for articles that were published from 1985 to 2020. The inclusion criteria were "urinary metabolites," "oral cancer/HNSCC," "body fluids," "tobacco," and "metabolomics." A total of 55 articles were collected which included laboratory studies, systematic reviews, and literature of urinary metabolites in tobacco users.
RESULTS
Most of the studies carried out show accurate results with high sensitivity of urinary metabolite biomarkers in individuals with tobacco-based habits and lesions caused by them.
CONCLUSION
The review indicates that urinary metabolite analysis demonstrates its applicability for the diagnosis and prognosis of disease. Urine is a remarkable and useful biofluid for routine testing and provides an excellent resource for the discovery of novel biomarkers, with an advantage over tissue biopsy samples due to the ease and less invasive nature of collection.
PubMed: 38707674
DOI: 10.4103/ccd.ccd_23_21 -
Neurobiology of Disease Jul 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial... (Meta-Analysis)
Meta-Analysis
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.
Topics: Humans; Autism Spectrum Disorder; Biomarkers; DNA, Mitochondrial; Mitochondria; Mitochondrial Diseases
PubMed: 38703861
DOI: 10.1016/j.nbd.2024.106520