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Antioxidants (Basel, Switzerland) Mar 2024Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis,... (Review)
Review
Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis, necroptosis, and autophagy. It is characterized by the accumulation of intracellular iron, overproduction of reactive oxygen species, depletion of glutathione, and extensive lipid peroxidation of lipids in the cell membrane. It was discovered that ferroptosis is interconnected with many diseases, such as neurodegenerative diseases, ischemia/reperfusion injury, cancer, and chronic kidney disease. Polyphenols, plant secondary metabolites known for many bioactivities, are being extensively researched in the context of their influence on ferroptosis which resulted in a great number of publications showing the need for a systematic review. In this review, an extensive literature search was performed. Databases (Scopus, Web of Science, PubMed, ScienceDirect, Springer) were searched in the time span from 2017 to November 2023, using the keyword "ferroptosis" alone and in combination with "flavonoid", "phenolic acid", "stilbene", "coumarin", "anthraquinone", and "chalcone"; after the selection of studies, we had 311 papers and 143 phenolic compounds. In total, 53 compounds showed the ability to induce ferroptosis, and 110 compounds were able to inhibit ferroptosis, and out of those compounds, 20 showed both abilities depending on the model system. The most researched compounds are shikonin, curcumin, quercetin, resveratrol, and baicalin. The most common modes of action are in the modulation of the Nrf2/GPX4 and Nrf2/HO-1 axis and the modulation of iron metabolism.
PubMed: 38539867
DOI: 10.3390/antiox13030334 -
Frontiers in Neuroscience 2024Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent...
Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies.
INTRODUCTION
Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT).
METHODS
We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design.
RESULTS
Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with (phylum Firmicutes) and positively correlated with sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition.
DISCUSSION
Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior.
SYSTEMATIC REVIEW REGISTRATION
https://clinicaltrials.gov/, CRD42020158734.
PubMed: 38516317
DOI: 10.3389/fnins.2024.1341656 -
Frontiers in Neuroscience 2024Cerebral ischaemic stroke is a common disease that poses a serious threat to human health. Butyrate is an important metabolite of intestinal microorganisms. Recent...
INTRODUCTION
Cerebral ischaemic stroke is a common disease that poses a serious threat to human health. Butyrate is an important metabolite of intestinal microorganisms. Recent studies have shown that butyrate has a significant protective effect in animal models of cerebral ischaemic injury.
OBJECTIVE
The aim of this study was to evaluate the protective effect of butyrate on cerebral ischaemic stroke by meta-analysis, aiming to provide a scientific basis for the clinical application of butyrate in patients with cerebral ischaemia.
MATERIALS AND METHODS
A systematic search was conducted for all relevant studies published before 23 January 2024, in PubMed, Web of Science, Cochrane Library, and Embase. Methodological quality was assessed using Syrcle's risk of bias tool for animal studies. Data were analysed using Rev Man 5.3 software.
RESULTS
A total of nine studies were included, and compared with controls, butyrate significantly increased BDNF levels in the brain (SMD = 2.33, 95%CI = [1.20, 3.47], < 0.005) and P-Akt expression (SMD = 3.53, 95% CI = [0.97, 6.10], < 0.05). Butyrate also decreased IL-β levels in the brain (SMD = -2.02, 95% CI = [-3.22, -0.81], < 0.005), TNF-α levels (SMD = -0.86, 95% CI = [-1.60, -0.12], < 0.05), and peripheral vascular IL-1β levels (SMD = -2.10, 95%CI = [-3.59, -0.61], < 0.05). In addition, butyrate reduced cerebral infarct volume (MD = -11.29, 95%CI = [-17.03, -5.54], < 0.05), mNSS score (MD = -2.86, 95%CI = [-4.12, -1.60], < 0.005), foot fault score (MD = -7.59, 95%CI = [-9.83, -5, 35], < 0.005), and Morris water maze time (SMD = -2.49, 95%CI = [-4.42, -0.55], < 0.05).
CONCLUSION
The results of this study indicate that butyrate has a protective effect on cerebral ischaemic stroke in animal models, and the mechanism is related to reducing inflammation and inhibiting apoptosis. It provides an evidence-based basis for the future clinical development of butyrate in the treatment of ischaemic stroke.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, CRD42023482844.
PubMed: 38486971
DOI: 10.3389/fnins.2024.1304906 -
International Journal of Surgery... Mar 2024The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this... (Meta-Analysis)
Meta-Analysis
Exhaled breath and urinary volatile organic compounds (VOCs) for cancer diagnoses, and microbial-related VOC metabolic pathway analysis: a systematic review and meta-analysis.
BACKGROUND
The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this study was to assess the diagnostic potential of exhaled breath and urinary VOCs in cancer detection. As VOCs are indicative of tumor and human metabolism, our work also sought to investigate the metabolic pathways linked to the development of cancerous tumors.
MATERIALS AND METHODS
An electronic search was performed in the PubMed database. Original studies on VOCs within exhaled breath and urine for cancer detection with a control group were included. A meta-analysis was conducted using a bivariate model to assess the sensitivity and specificity of the VOCs for cancer detection. Fagan's nomogram was designed to leverage the findings from our diagnostic analysis for the purpose of estimating the likelihood of cancer in patients. Ultimately, MetOrigin was employed to conduct an analysis of the metabolic pathways associated with VOCs in relation to both human and/or microbiota.
RESULTS
The pooled sensitivity, specificity and the area under the curve for cancer screening utilizing exhaled breath and urinary VOCs were determined to be 0.89, 0.88, and 0.95, respectively. A pretest probability of 51% can be considered as the threshold for diagnosing cancers with VOCs. As the estimated pretest probability of cancer exceeds 51%, it becomes more appropriate to emphasize the 'ruling in' approach. Conversely, when the estimated pretest probability of cancer falls below 51%, it is more suitable to emphasize the 'ruling out' approach. A total of 14, 14, 6, and 7 microbiota-related VOCs were identified in relation to lung, colorectal, breast, and liver cancers, respectively. The enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in the aforementioned tumor types.
CONCLUSIONS
The analysis of exhaled breath and urinary VOCs showed promise for cancer screening. In addition, the enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in four tumor types, namely lung, colorectum, breast and liver. These findings hold significant implications for the prospective clinical application of multiomics correlation in disease management and the exploration of potential therapeutic targets.
Topics: Humans; Volatile Organic Compounds; Prospective Studies; Breath Tests; Liver Neoplasms; Metabolic Networks and Pathways
PubMed: 38484261
DOI: 10.1097/JS9.0000000000000999 -
Frontiers in Nutrition 2024Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome...
BACKGROUND
Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome (MetS), while dietary SM supplementation may maintain lipid metabolism and prevent or alleviate MetS. Therefore, we hypothesized that dietary SM supplementation is beneficial for human health.
AIMS
In order to examine the impacts of dietary SM on metabolic indexes in adults without MetS, we performed a meta-analysis to test our hypothesis.
METHODS
A comprehensive search was performed to retrieve randomized controlled trials that were conducted between 2003 and 2023 to examine the effects of dietary SM supplementation on metabolic parameters in the Cochrane Library, PubMed, Web of Science, Embase, and ClinicalTrials.gov databases. RevMan 5.4 and Stata 14.0 software were used for meta-analysis, a sensitivity analysis, the risk of bias, and the overall quality of the resulted evidence.
RESULTS
Eventually, 10 articles were included in this meta-analysis. Dietary SM supplementation did not affect the endline blood SM level. When compared to the control, SM supplementation reduced the blood total cholesterol level [MD: -12.97, 95% CI: (-14.57, -11.38), < 0.00001], low-density lipoprotein cholesterol level [MD: -6.62, 95% CI: (-10.74, -2.49), = 0.002], and diastolic blood pressure [MD: -3.31; 95% CI (-4.03, -2.58), < 0.00001] in adults without MetS. The supplementation also increased high-density lipoprotein level [MD:1.41, 95% CI: (0.94, 1.88), < 0.00001] and muscle fiber conduction velocity [MD: 95% 1.21 CI (0.53, 1.88), = 0.0005]. The intake of SM had no effect on the blood phospholipids and lyso-phosphatidylcholine, but slightly decreased phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol concentrations. Dietary SM supplementation reduced insulin level [MD: -0.63; 95% CI (-0.96, -0.31), = 0.0001] and HOMA-IR [MD: -0.23; 95% CI (-0.31, -0.16), < 0.00001] without affecting blood levels of glucose and inflammatory cytokines.
CONCLUSION
Overall, dietary SM supplementation had a protective effect on blood lipid profiles and insulin level, but had limited impacts on other metabolic parameters in adults without MetS. More clinical trials and basic research are required.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42023438460.
PubMed: 38463938
DOI: 10.3389/fnut.2024.1363077 -
Redox Biology May 2024This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and... (Review)
Review
This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and excretion (ADME) of phenolic metabolites and its determinants. Human studies were included investigating the metabolism and bioavailability of (poly)phenols and reporting IIV. One hundred fifty-three studies met the inclusion criteria. Inter-individual differences were mainly related to gut microbiota composition and activity but also to genetic polymorphisms, age, sex, ethnicity, BMI, (patho)physiological status, and physical activity, depending on the (poly)phenol sub-class considered. Most of the IIV has been poorly characterised. Two major types of IIV were observed. One resulted in metabolite gradients that can be further classified into high and low excretors, as seen for all flavonoids, phenolic acids, prenylflavonoids, alkylresorcinols, and hydroxytyrosol. The other type of IIV is based on clusters of individuals defined by qualitative differences (producers vs. non-producers), as for ellagitannins (urolithins), isoflavones (equol and O-DMA), resveratrol (lunularin), and preliminarily for avenanthramides (dihydro-avenanthramides), or by quali-quantitative metabotypes characterized by different proportions of specific metabolites, as for flavan-3-ols, flavanones, and even isoflavones. Future works are needed to shed light on current open issues limiting our understanding of this phenomenon that likely conditions the health effects of dietary (poly)phenols.
Topics: Humans; Biological Availability; Phenols; Flavonoids; Isoflavones; Diet
PubMed: 38428187
DOI: 10.1016/j.redox.2024.103095 -
Journal of Cannabis Research Feb 2024The primary components driving the current commercial fascination with cannabis products are phytocannabinoids, a diverse group of over 100 lipophilic secondary... (Review)
Review
BACKGROUND
The primary components driving the current commercial fascination with cannabis products are phytocannabinoids, a diverse group of over 100 lipophilic secondary metabolites derived from the cannabis plant. Although numerous phytocannabinoids exhibit pharmacological effects, the foremost attention has been directed towards Δ-tetrahydrocannabinol (THC) and cannabidiol, the two most abundant phytocannabinoids, for their potential human applications. Despite their structural similarity, THC and cannabidiol diverge in terms of their psychotropic effects, with THC inducing notable psychological alterations. There is a clear need for accurate and rapid THC measurement methods that offer dependable, readily accessible, and cost-effective analytical information. This review presents a comprehensive view of the present state of alternative technologies that could potentially facilitate the creation of portable devices suitable for on-site usage or as personal monitors, enabling non-intrusive THC measurements.
METHOD
A literature survey from 2017 to 2023 on the development of portable technologies and commercial products to detect THC in biofluids was performed using electronic databases such as PubMed, Scopus, and Google Scholar. A systematic review of available literature was conducted using Preferred Reporting Items for Systematic. Reviews and Meta-analysis (PRISMA) guidelines.
RESULTS
Eighty-nine studies met the selection criteria. Fifty-seven peer-reviewed studies were related to the detection of THC by conventional separation techniques used in analytical laboratories that are still considered the gold standard. Studies using optical (n = 12) and electrochemical (n = 13) portable sensors and biosensors were also identified as well as commercially available devices (n = 7).
DISCUSSION
The landscape of THC detection technology is predominantly shaped by immunoassay tests, owing to their established reliability. However, these methods have distinct drawbacks, particularly for quantitative analysis. Electrochemical sensing technology holds great potential to overcome the challenges of quantification and present a multitude of advantages, encompassing the possibility of miniaturization and diverse modifications to amplify sensitivity and selectivity. Nevertheless, these sensors have considerable limitations, including non-specific interactions and the potential interference of compounds and substances existing in biofluids.
CONCLUSION
The foremost challenge in THC detection involves creating electrochemical sensors that are both stable and long-lasting while exhibiting exceptional selectivity, minimal non-specific interactions, and decreased susceptibility to matrix interferences. These aspects need to be resolved before these sensors can be successfully introduced to the market.
PubMed: 38414071
DOI: 10.1186/s42238-024-00216-0 -
Frontiers in Immunology 2024Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the release of mediators. However, the well-known underlying pathological mechanisms do not fully explain the whole variety of clinical and immunological presentations. We performed a systemic review of proteomic and metabolomic studies and analyzed the extracted data to improve our understanding and identify potential new biomarkers of anaphylaxis.
METHODS
Proteomic and metabolomic studies in both human subjects and experimental models were extracted and selected through a systematic search conducted on databases such as PubMed, Scopus, and Web of Science, up to May 2023.
RESULTS
Of 137 retrieved publications, we considered 12 for further analysis, including seven on proteome analysis and five on metabolome analysis. A meta-analysis of the four human studies identified 118 proteins with varying expression levels in at least two studies. Beside established pathways of mast cells and basophil activation, functional analysis of proteomic data revealed a significant enrichment of biological processes related to neutrophil activation and platelet degranulation and metabolic pathways of arachidonic acid and icosatetraenoic acid. The pathway analysis highlighted also the involvement of neutrophil degranulation, and platelet activation. Metabolome analysis across different models showed 13 common metabolites, including arachidonic acid, tryptophan and lysoPC(18:0) lysophosphatidylcholines.
CONCLUSION
Our review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions. These findings, derived from a limited number of publications, necessitate confirmation through human studies with larger sample sizes and could contribute to the development of new biomarkers for anaphylaxis.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024506246.
Topics: Humans; Anaphylaxis; Arachidonic Acid; Proteomics; Allergens; Biomarkers
PubMed: 38384462
DOI: 10.3389/fimmu.2024.1328212 -
Nutrients Jan 2024Over recent decades, a growing body of evidence has emerged linking the composition of the gut microbiota to sleep regulation. Interestingly, the prevalence of sleep... (Review)
Review
BACKGROUND
Over recent decades, a growing body of evidence has emerged linking the composition of the gut microbiota to sleep regulation. Interestingly, the prevalence of sleep disorders is commonly related to cardiometabolic comorbidities such as diabetes, impaired lipid metabolism, and metabolic syndrome (MetS). In this complex scenario, the role of the gut-brain axis as the main communicating pathway between gut microbiota and sleep regulation pathways in the brain reveals some common host-microbial biomarkers in both sleep disturbances and MetS. As the biological mechanisms behind this complex interacting network of neuroendocrine, immune, and metabolic pathways are not fully understood yet, the present systematic review aims to describe common microbial features between these two unrelated chronic conditions.
RESULTS
This systematic review highlights a total of 36 articles associating the gut microbial signature with MetS or sleep disorders. Specific emphasis is given to studies evaluating the effect of dietary patterns, dietary supplementation, and probiotics on MetS or sleep disturbances.
CONCLUSIONS
Dietary choices promote microbial composition and metabolites, causing both the amelioration and impairment of MetS and sleep homeostasis.
Topics: Humans; Metabolic Syndrome; Brain-Gut Axis; Probiotics; Diet; Gastrointestinal Microbiome; Dysbiosis
PubMed: 38337675
DOI: 10.3390/nu16030390 -
CNS Neuroscience & Therapeutics Feb 2024Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and... (Review)
Review
BACKGROUND AND OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS.
METHODS
A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS.
RESULTS
A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory.
CONCLUSIONS
The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.
Topics: Humans; Diffusion Tensor Imaging; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Frontotemporal Dementia; Magnetic Resonance Imaging; Hippocampus; Biomarkers; Neuropsychological Tests; Atrophy
PubMed: 38334254
DOI: 10.1111/cns.14578