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Biomolecules Mar 2022RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination... (Review)
Review
RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination of Adenosine (A) to Inosine (I) or Cytidine (C) to Uridine (U) is the most common type of mammalian RNA editing. It occurs as a nuclear co- and/or post-transcriptional event catalyzed by ADARs (Adenosine deaminases acting on RNA) and APOBECs (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like genes). RNA editing may modify the structure, stability, and processing of a transcript. This review focuses on RNA editing in psychiatric, neurological, neurodegenerative (NDs), and autoimmune brain disorders in humans and rodent models. We discuss targeted studies that focus on RNA editing in specific neuron-enriched transcripts with well-established functions in neuronal activity, and transcriptome-wide studies, enabled by recent technological advances. We provide comparative editome analyses between human disease and corresponding animal models. Data suggest RNA editing to be an emerging mechanism in disease development, displaying common and disease-specific patterns. Commonly edited RNAs represent potential disease-associated targets for therapeutic and diagnostic values. Currently available data are primarily descriptive, calling for additional research to expand global editing profiles and to provide disease mechanistic insights. The potential use of RNA editing events as disease biomarkers and available tools for RNA editing identification, classification, ranking, and functional characterization that are being developed will enable comprehensive analyses for a better understanding of disease(s) pathogenesis and potential cures.
Topics: Adenosine; Adenosine Deaminase; Animals; Brain; Brain Diseases; Mammals; Neurodegenerative Diseases; RNA; RNA Editing
PubMed: 35327657
DOI: 10.3390/biom12030465 -
Frontiers in Immunology 2022Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently...
Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently treated, therapies for progression are scarce and suboptimal, and biomarkers to predict the disease course are insufficient. Cure or preventive measures for MS require knowledge of core pathological events at the site of the tissue damage. Novelties in systems biology have emerged and paved the way for a more fine-grained understanding of key pathological pathways within the CNS, but they have also raised questions still without answers. Here, we systemically review the power of tissue and single-cell/nucleus CNS omics and discuss major gaps of integration into the clinical practice. Systemic search identified 49 transcriptome and 11 proteome studies of the CNS from 1997 till October 2021. Pioneering molecular discoveries indicate that MS affects the whole brain and all resident cell types. Despite inconsistency of results, studies imply increase in transcripts/proteins of semaphorins, heat shock proteins, myelin proteins, apolipoproteins and HLAs. Different lesions are characterized by distinct astrocytic and microglial polarization, altered oligodendrogenesis, and changes in specific neuronal subtypes. In all white matter lesion types, are highly expressed, and STAT6- and TGFβ-signaling are increased. In the grey matter lesions, TNF-signaling seems to drive cell death, and especially -expressing neurons may be susceptible to neurodegeneration. The vast heterogeneity at both cellular and lesional levels may underlie the clinical heterogeneity of MS, and it may be more complex than the current disease phenotyping in the clinical practice. Systems biology has not solved the mystery of MS, but it has discovered multiple molecules and networks potentially contributing to the pathogenesis. However, these results are mostly descriptive; focused functional studies of the molecular changes may open up for a better interpretation. Guidelines for acceptable quality or awareness of results from low quality data, and standardized computational and biological pipelines may help to overcome limited tissue availability and the "snap shot" problem of omics. These may help in identifying core pathological events and point in directions for focus in clinical prevention.
Topics: Brain; Humans; Multiple Sclerosis; Proteome; Transcriptome; White Matter
PubMed: 35309325
DOI: 10.3389/fimmu.2022.761225 -
Effects of Hazelnut Consumption on Cardiometabolic Risk Factors and Acceptance: A Systematic Review.International Journal of Environmental... Mar 2022Despite being rich sources of monounsaturated fat and a number of vitamins, minerals, and phytonutrients, hazelnuts have received less attention than some other nut... (Review)
Review
Despite being rich sources of monounsaturated fat and a number of vitamins, minerals, and phytonutrients, hazelnuts have received less attention than some other nut types. A qualitative systematic review was carried out to determine the effects of hazelnut consumption on acceptance and markers of cardiometabolic health, including blood lipids and lipoproteins, apolipoproteins A1 and B100, body weight and composition, blood pressure, glycemia, antioxidant status, oxidative stress, inflammation, and endothelial function. In total, 22 intervention studies (25 publications) met our inclusion criteria. The findings indicate some improvements in cardiometabolic risk factors; however, limitations in study design mean interpretation is problematic. The inclusion of hazelnuts in the diet did not adversely affect body weight and composition. Acceptance of hazelnuts remained stable over time confirming nut consumption guidelines are feasible and sustainable. Future studies using more robust study designs in a variety of populations are required to draw more definitive conclusions on the health benefits of hazelnut consumption.
Topics: Body Weight; Cardiometabolic Risk Factors; Corylus; Diet; Lipids
PubMed: 35270573
DOI: 10.3390/ijerph19052880 -
BMJ Open Feb 2022Despite the uptake of nutrigenetic testing through direct-to-consumer services and healthcare professionals, systematic reviews determining scientific validity are...
OBJECTIVES
Despite the uptake of nutrigenetic testing through direct-to-consumer services and healthcare professionals, systematic reviews determining scientific validity are limited in this field. The objective of this review was to: retrieve, synthesise and assess the quality of evidence (confidence) for nutrigenetic approaches related to the effect of genetic variation on plasma lipid, lipoprotein and apolipoprotein responsiveness to omega-3 fatty acid intake.
DESIGN
A systematic review was conducted using three search engines (Embase, Web of Science and Medline) for articles published up until 1 August 2020. We aimed to systematically search, identify (select) and provide a narrative synthesis of all studies that assessed nutrigenetic associations/interactions for genetic variants (comparators) influencing the plasma lipid, lipoprotein and/or apolipoprotein response (outcomes) to omega-3 fatty acid intake (intervention/exposure) in humans-both paediatric and adult populations (population). We further aimed to assess the overall quality of evidence for specific priority nutrigenetic associations/interactions based on the following inclusion criteria: nutrigenetic associations/interactions reported for the same genetic variants (comparators) influencing the same plasma lipid, lipoprotein and/or apolipoprotein response (outcomes) to omega-3 fatty acid intake (intervention/exposure) in humans-both paediatric and adult populations (population) in at least two independent studies, irrespective of the findings. Risk of bias was assessed in individual studies. Evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach with a modification to further consider biological plausibility.
RESULTS
Out of 1830 articles screened, 65 met the inclusion criteria for the narrative synthesis (n=23 observational, n=42 interventional); of these, 25 met the inclusion criteria for GRADE evidence evaluation. Overall, current evidence is insufficient for gene-diet associations related to omega-3 fatty acid intake on plasma apolipoproteins, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol and LDL particle size. However, there is strong (GRADE rating: moderate quality) evidence to suggest that male -E4 carriers (rs429358, rs7412) exhibit significant triglyceride reductions in response to omega-3-rich fish oil with a dose-response effect. Moreover, strong (GRADE rating: high quality) evidence suggests that a 31-SNP nutrigenetic risk score can predict plasma triglyceride responsiveness to omega-3-rich fish oil in adults with overweight/obesity from various ethnicities.
CONCLUSIONS
Most evidence in this area is weak, but two specific nutrigenetic interactions exhibited strong evidence, with generalisability limited to specific populations.
PROSPERO REGISTRATION NUMBER
CRD42020185087.
Topics: Apolipoproteins; Child; Cholesterol; Fatty Acids, Omega-3; Humans; Lipoproteins; Male; Nutrigenomics; Triglycerides
PubMed: 35193914
DOI: 10.1136/bmjopen-2021-054417 -
Disease Markers 2022Rising studies indicate that the apolipoprotein E (APOE) gene is related to the susceptibility of ischemic stroke (IS). However, certain consensus is limited by the lack... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rising studies indicate that the apolipoprotein E (APOE) gene is related to the susceptibility of ischemic stroke (IS). However, certain consensus is limited by the lack of a large sample size of researches. This meta-analysis was performed to explore the potential association between the APOE gene and IS.
METHODS
To identify relevant case control studies in English publications by October 2020, we searched PubMed, Embase, Web of Science, and the Cochrane Library. Pooled odds ratios (ORs) with fixed- or random-effect models and corresponding 95% confidence intervals (CIs) were calculated to analyze potential associations.
RESULTS
A total of 55 researches from 32 countries containing 12207 IS cases and 27742 controls were included. The association between APOE gene 4 mutation and IS was confirmed (4 vs. 3 allele: pooled OR = 1.374, 95% CI, 1.214-1.556; 2/4 vs. 3/3: pooled OR = 1.233, 95% CI, 1.056-1.440; 3/4 vs. 3/3: pooled OR = 1.340, 95% CI, 1.165-1.542; 4/4 vs. 3/3: pooled OR = 1.833, 95% CI, 1.542-2.179; and APOE 4 carriers vs. non-4 carriers: pooled OR = 1.377; 95% CI, 1.203-1.576). Interestingly, APOE 4 mutation showed a dose-response correlation with IS risk (4/4 vs. 2/4: pooled OR = 1.625; 95% CI, 1.281-2.060; 4/4 vs. 3/4: pooled OR = 1.301; 95% CI, 1.077-1.571). Similar conclusions were drawn in the small artery disease (SAD) subtype, but not in large artery atherosclerosis (LAA) or in cardioaortic embolism (CE), by subgroup analysis.
CONCLUSIONS
These observations reveal that specific APOE 4 mutation was significantly associated with the risk of IS in a dose-dependent manner, while APOE 4 mutation was related to SAD subtype onset without a cumulative effect.
Topics: Apolipoprotein E4; Humans; Ischemic Stroke; Polymorphism, Genetic; Risk Factors
PubMed: 35154509
DOI: 10.1155/2022/1407183 -
Frontiers in Aging Neuroscience 2021Possession of one or two e4 alleles of the apolipoprotein E () gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity...
INTRODUCTION
Possession of one or two e4 alleles of the apolipoprotein E () gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently.
METHOD
We conducted a systematic review and meta-analysis of studies which assessed differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function in healthy adults. Searches were carried out in PubMed, SCOPUS, Web of Science and PsycInfo.
RESULTS
Thirty studies were included from 4,896 papers screened. Carriers of the e4 allele gained the same benefit from physical activity as non-carriers on most outcomes. For brain activation, e4 carriers appeared to gain a greater benefit from physical activity on task-related and resting-state activation and resting-state functional connectivity compared to non-carriers. analysis identified possible compensatory mechanisms allowing e4 carriers to maintain cognitive function.
DISCUSSION
Though there is evidence suggesting physical activity may benefit e4 carriers differently compared to non-carriers, this may vary by the specific brain health outcome, perhaps limited to brain activation. Further research is required to confirm these findings and elucidate the mechanisms.
PubMed: 35153725
DOI: 10.3389/fnagi.2021.815439 -
Acta Neuropathologica Communications Jan 2022The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain...
Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature.
BACKGROUND
The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain controversial. Some studies suggest that moderate to severe TBI is sufficient to promote tau pathology; however, others suggest that it is simply a consequence of aging. We therefore conducted a systematic narrative review of the literature addressing whether a single moderate to severe head injury leads to long-term development of tauopathy in both humans and animal models.
METHODS
Studies considered for inclusion in this review assessed a single moderate to severe TBI, assessed tau pathology at long-term timepoints post-injury, comprised experimental or observational studies, and were peer-reviewed and published in English. Databases searched included: PUBMED, NCBI-PMC, EMBASE, Web of Science, Academic Search Premiere, and APA Psychnet. Search results were uploaded to Covidence®, duplicates were removed, and articles underwent an abstract and full-text screening process. Data were then extracted and articles assessed for risk of bias.
FINDINGS
Of 4,150 studies screened, 26 were eligible for inclusion, of which 17 were human studies, 8 were preclinical animal studies, and 1 included both human and preclinical animal studies. Most studies had low to moderate risk of bias. Most human and animal studies (n = 12 and 9, respectively) suggested that a single moderate to severe TBI resulted in greater development of long-term tauopathy compared to no history of head injury. This conclusion should be interpreted with caution, however, due to several limitations: small sample sizes; inconsistencies in controlling for confounding factors that may have affected tau pathology (e.g., family history of dementia or neurological illnesses, apolipoprotein E genotype, etc.), inclusion of mostly males, and variation in reporting injury parameters.
INTERPRETATION
Results indicate that a single moderate to severe TBI leads to greater chronic development of tauopathy compared to no history of head injury. This implies that tau pathology induced may not be transient, but can progressively develop over time in both humans and animal models. Targeting these tau changes for therapeutic intervention should be further explored to elucidate if disease progression can be reversed or mitigated.
Topics: Animals; Brain; Brain Injuries, Traumatic; Disease Models, Animal; Humans; Tauopathies
PubMed: 35101132
DOI: 10.1186/s40478-022-01311-0 -
European Journal of Nutrition Jun 2022Oat supplementation interventions (OSIs) may have a beneficial effect on cardiovascular disease (CVD) risk. However, dietary background can modulate such effect. This... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Oat supplementation interventions (OSIs) may have a beneficial effect on cardiovascular disease (CVD) risk. However, dietary background can modulate such effect. This systematic review assesses the effects of OSIs on CVD risk markers among adults, accounting for different dietary backgrounds or control arms.
METHODS
We included randomized clinical trials (RCTs) that assessed the effect of oat, oat beta-glucan-rich extracts or avenanthramides on CVD risk markers.
RESULTS
Seventy-four RCTs, including 4937 predominantly hypercholesterolemic, obese subjects, with mild metabolic disturbances, were included in the systematic review. Of these, 59 RCTs contributed to the meta-analyses. Subjects receiving an OSI, compared to control arms without oats, had improved levels of total cholesterol (TC) [weighted mean difference and (95% CI) - 0.42 mmol/L, (- 0.61; - 0.22)], LDL cholesterol [- 0.29 mmol/L, (- 0.37; - 0.20)], glucose [- 0.25 nmol/L, (- 0.36; - 0.14)], body mass index [- 0.13 kg/m, (- 0.26; - 0.01)], weight [- 0.94 kg, (- 1.84: - 0.05)], and waist circumference [- 1.06 cm, (- 1.85; - 0.27)]. RCTs on inflammation and/or oxidative stress markers were scarce and with inconsistent findings. RCTs comparing an OSI to heterogeneous interventions (e.g., wheat, eggs, rice, etc.), showed lowered levels of glycated haemoglobin, diastolic blood pressure, HDL cholesterol and apolipoprotein B. The majority of included RCTs (81.1%) had some concerns for risk of bias.
CONCLUSION
Dietary OSIs resulted in lowered levels of blood lipids and improvements in anthropometric parameters among participants with predominantly mild metabolic disturbances, regardless of dietary background or control. Further high-quality trials are warranted to establish the role of OSIs on blood pressure, glucose homeostasis and inflammation markers.
Topics: Adult; Avena; Biomarkers; Cardiovascular Diseases; Cholesterol; Dietary Supplements; Glucose; Humans; Inflammation; Randomized Controlled Trials as Topic
PubMed: 34977959
DOI: 10.1007/s00394-021-02763-1 -
Nutrition Reviews Apr 2022Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and...
CONTEXT
Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and lipoprotein subfractions.
OBJECTIVE
To systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms.
DATA SOURCES
Following PRISMA, all human and ex vivo studies with an alcohol intake up to 60 g/d were included from 8 databases.
DATA EXTRACTION
A total of 17 478 studies were screened, and data were extracted from 37 intervention and 77 observational studies.
RESULTS
Alcohol intake was positively associated with all HDL subfractions. A few studies found lower levels of small LDLs, increased average LDL particle size, and nonlinear relationships to apolipoprotein B-containing lipoproteins. Cholesterol efflux capacity and paraoxonase activity were consistently increased. Several studies had unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies.
CONCLUSIONS
Up to 60 g/d alcohol can cause changes in lipoprotein subfractions and related mechanisms that could influence cardiovascular health.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. 98955.
Topics: Alcohol Drinking; Apolipoproteins B; Cardiovascular Diseases; Cholesterol, HDL; Humans; Lipoproteins; Lipoproteins, LDL
PubMed: 34957513
DOI: 10.1093/nutrit/nuab102 -
Maturitas Jan 2022Menopause is accompanied by many metabolic changes, increasing the risk of cardiometabolic diseases. The impact of diet, as a modifiable lifestyle factor, on... (Review)
Review
OBJECTIVES
Menopause is accompanied by many metabolic changes, increasing the risk of cardiometabolic diseases. The impact of diet, as a modifiable lifestyle factor, on cardiovascular health in general populations has been well established. The purpose of this systematic review is to summarize the evidence on the effects of whole diet on lipid profile, glycemic indices, and blood pressure in postmenopausal women.
METHODS
Embase, Medline, Cochrane Central Register of Controlled Trials, and Google Scholar were searched from inception to February 2021. We included controlled clinical trials in postmenopausal women that assessed the effect of a whole-diet intervention on lipid profile, glycemic indices, and/or blood pressure. The risk of bias in individual studies was assessed using RoB 2 and ROBINS-I tools.
SUMMARY OF EVIDENCE
Among 2,134 references, 21 trials met all eligibility criteria. Overall, results were heterogenuous and inconsistent. Compared to control diets, some studies showed that participants experienced improvements in total cholesterol (TC), low-density lipoprotein cholesterol (LDL), systolic blood pressure (SBP), fasting blood sugar (FBS), and apolipoprotein A (Apo-A) after following fat-modified diets, but some adverse effects on triglycerides (TG), very low-density lipoprotein cholesterol (VLDL), lipoprotein(a) (Lp(a)), and high-density lipoprotein cholesterol (HDL) concentrations were also observed. A limited number of trials found some effects of the Paleolithic, weight-loss, plant-based, or energy-restricted diets, or of following American Heart Association recommendations on TG, TC, HDL, insulin, FBS, or insulin resistance.
CONCLUSION
Current evidence suggests that diet may affect levels of some lipid profile markers, glycemic indices, and blood pressure among postmenopausal women. However, due to the large heterogeneity in intervention diets, comparison groups, intervention durations, and population characteristics, findings are inconclusive. Further well-designed clinical trials are needed on dietary interventions to reduce cardiovascular risk in postmenopausal women.
Topics: Cardiovascular Diseases; Cholesterol, HDL; Diet; Female; Heart Disease Risk Factors; Humans; Postmenopause; Risk Factors; Triglycerides
PubMed: 34876248
DOI: 10.1016/j.maturitas.2021.10.001