-
Journal of Digestive Diseases Aug 2022To summarize the associations between potential causal factors and colorectal cancer (CRC) risk based on existing Mendelian randomization studies. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To summarize the associations between potential causal factors and colorectal cancer (CRC) risk based on existing Mendelian randomization studies.
METHODS
This systematic review and meta-analysis involved a literature search in Embase and Medline. All published articles using Mendelian randomization to explore potential causal factors of CRC were included. Studies that reported Mendelian randomization estimates of standard deviation changes in exposures were included in the meta-analysis. Subgroup analyses based on sex and anatomical sites were performed.
RESULTS
One hundred and ninety studies presented in 51 articles were included in systematic review, and 114 studies conducted in 32 articles were included in the meta-analysis. Adult body mass index, waist circumference, waist hip ratio, body height, body fat percentage, arm fat ratio, childhood obesity, lifetime cigarette consumption, short sleep, coffee consumption, and blood levels of vitamin B , arachidonic acid, stearic acid, and insulin-like growth factor binding protein 3 were positively associated with CRC risk. Conversely, acceleration-vector-magnitude physical activity, milk consumption, and blood levels of adiponectin, linoleic acid, α-linolenic acid, oleic acid, palmitoleic acid, interleukin-6 receptor subunit-α, and tumor necrosis factor were inversely associated with CRC risk.
CONCLUSIONS
Most obesity-related anthropometric characteristics, several unhealthy lifestyles, and blood levels of some micronutrients, fatty acids, and diabetes-related biomarkers were positively associated with CRC risk. In contrast, some lifestyles and blood levels of some fatty acids and inflammatory biomarkers were inversely associated with CRC risk. Future studies with more valid genetic variants are needed for factors with discrepancies between Mendelian randomization and epidemiological studies.
Topics: Child; Adult; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Colorectal Neoplasms; Pediatric Obesity; Risk Factors; Biomarkers; Fatty Acids; Genome-Wide Association Study
PubMed: 36169182
DOI: 10.1111/1751-2980.13130 -
Molecular Psychiatry Jul 2016The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies... (Meta-Analysis)
Meta-Analysis Review
The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication of these findings and to assess their specificity for ADHD.
Topics: Adult; Alleles; Attention Deficit Disorder with Hyperactivity; Biomarkers; Docosahexaenoic Acids; Dopamine Plasma Membrane Transport Proteins; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Male; Methylphenidate; Minisatellite Repeats; Nerve Tissue Proteins; Pharmacogenetics; Polymorphism, Genetic; Receptors, Dopamine D4
PubMed: 27217152
DOI: 10.1038/mp.2016.74 -
Nutrients Feb 2023Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasingly, studies have discovered that different fatty acids (Fas) are linked to colorectal cancer (CRC) risk.
METHODS
We systematically searched Embase and Medline databases to identify eligible studies that examined the associations of different types of Fas with CRC risk. The effect estimates and their 95% confidence intervals (Cis) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to examine the robustness of the study findings.
RESULTS
This study evaluated the associations of 28 dietary and 18 blood Fas with CRC risk by summarizing the most updated evidence from 54 observational and four Mendelian Randomization (MR) studies. The present findings suggested that high dietary intake of eicosapentaenoic acid (EPA), docosahexanoic acid (DHA), and docosapentaenoic acid (DPA) are related to low risk of CRC, while the -6/-3 PUFA ratio and trans-FA are related to high risk of CRC. The summary of all cohort studies found that a high intake of SFA and DHA was a protective factor for CRC, and a high intake of the -6/-3 PUFA ratio was a risk factor for CRC. In the subgroup analysis of cancer subsites, we found that the dietary intake of linoleic acid (LA) and trans-FA are risk factors, while DPA is a protective factor for colon cancer. High dietary DHA intake was associated with a lower risk of rectal cancer, while the dietary -6/-3 PUFA ratio was associated with a higher risk of rectal cancer. Meta-analysis of blood FA levels showed a significant reverse association between blood pentadecanoic acid and CRC risk, whilst other blood Fas showed no significant association with CRC risk. All included MR studies showed that high plasma arachidonic acid (AA) is associated with increased CRC risk.
CONCLUSIONS
Current evidence on the dietary intake and blood levels of Fas in relation to CRC risk is less consistent. Future studies are needed to investigate how the metabolism of Fas contributes to CRC development.
Topics: Humans; Fatty Acids; Fatty Acids, Omega-3; Eating; Risk Factors; Colorectal Neoplasms; Rectal Neoplasms; Observational Studies as Topic
PubMed: 36771436
DOI: 10.3390/nu15030730 -
JPEN. Journal of Parenteral and Enteral... Sep 2015Acute respiratory disease syndrome (ARDS) is a common complication of critical illness, associated with significant morbidity, prolonged intensive care unit (ICU) and... (Meta-Analysis)
Meta-Analysis Review
Acute respiratory disease syndrome (ARDS) is a common complication of critical illness, associated with significant morbidity, prolonged intensive care unit (ICU) and hospital stay, and increased mortality. Inflammation plays a central role in ARDS, with inflammatory eicosanoid mediators produced from the ω-6 fatty acid arachidonic acid, such as leukotriene B4, being involved. The ω-3 fatty acids found in fish oil exert anti-inflammatory effects, including decreasing production of inflammatory eicosanoids from arachidonic acid. The ω-3 fatty acids are effective in models relevant to ARDS. Several randomized controlled trials of enteral formulas rich in ω-3 fatty acids, often in combination with other bioactive substances, have been conducted in patients with ARDS. Four of these trials reported marked clinical benefits, 2 reported no effect, and 1 reported a negative impact. A systematic review and meta-analysis of these 7 trials identified no overall effect on ventilator-free days or on ICU-free days. There was a small reduction in ICU length of stay and no overall effect on mortality. However, the authors formally identified that trials that used high fat in both treatment and control groups showed a significant reduction in mortality, while trials that used a high, or higher, fat treatment and a low-fat control group showed a trend toward an increase in mortality. It is concluded that differences in outcome reported among these studies largely relate to the relative fat contents of the treatment and control formulas. Further, it is concluded that high-fat enteral formulas should not be used in this patient group.
Topics: Critical Illness; Fatty Acids, Omega-3; Fish Oils; Humans; Inflammation; Intensive Care Units; Length of Stay; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome
PubMed: 25533963
DOI: 10.1177/0148607114565613 -
International Journal of Molecular... May 2023Arachidonic acid (AA) is a polyunsaturated fatty acid that is involved in male fertility. Human seminal fluid contains different prostaglandins: PGE (PGE and PGE), PGF,... (Review)
Review
Arachidonic acid (AA) is a polyunsaturated fatty acid that is involved in male fertility. Human seminal fluid contains different prostaglandins: PGE (PGE and PGE), PGF, and their specific 19-hydroxy derivatives, 18,19-dehydro derivatives of PGE and PGE. The objective of this study is to synthesize the available literature of in vivo animal studies and human clinical trials on the association between the AA pathway and male fertility. PGE is significantly decreased in the semen of infertile men, suggesting the potential for exploitation of PGE agonists to improve male fertility. Indeed, ibuprofen can affect male fertility by promoting alterations in sperm function and standard semen parameters. The results showed that targeting the AA pathways could be an attractive strategy for the treatment of male fertility.
Topics: Animals; Male; Humans; Semen; Arachidonic Acid; Prostaglandins E; Prostaglandins; Fertility
PubMed: 37175913
DOI: 10.3390/ijms24098207 -
Cerebrovascular Diseases Extra 2014Arachidonic acid (ARA) is a precursor of various lipid mediators. ARA metabolites such as thromboxane A2 cause platelet aggregation and vasoconstriction, thus may lead... (Review)
Review
BACKGROUND
Arachidonic acid (ARA) is a precursor of various lipid mediators. ARA metabolites such as thromboxane A2 cause platelet aggregation and vasoconstriction, thus may lead to atherosclerotic disease. It is unclear whether dietary ARA influences the ARA-derived lipid mediator balance and the risk for atherosclerotic diseases, such as cerebral ischemia. Considering the function of ARA in atherosclerosis, it is reasonable to focus on the atherothrombotic type of cerebral ischemia risk. However, no systematic reviews or meta-analyses have been conducted to evaluate the effect of habitual ARA exposure on cerebral ischemia risk. We aimed to systematically evaluate observational studies available on the relationship between ARA exposure and the atherothrombotic type of cerebral ischemia risk in free-living populations.
SUMMARY
The PubMed database was searched for articles registered up to June 24, 2014. We designed a PubMed search formula as follows: key words for humans AND brain ischemia AND study designs AND ARA exposure. Thirty-three articles were reviewed against predefined criteria. There were 695 bibliographies assessed from the articles that included both ARA and cerebral ischemia descriptions. Finally, we identified 11 eligible articles and categorized them according to their reporting and methodological quality. We used the Strengthening the Reporting of Observational Studies in Epidemiology Statement (STROBE) checklist to score the reporting quality. The methodological quality was qualitatively assessed based on the following aspects: subject selection, ARA exposure assessment, outcome diagnosis, methods for controlling confounders, and statistical analysis. We did not conduct a meta-analysis due to the heterogeneity among the studies. All eligible studies measured blood ARA levels as an indicator of exposure. Our literature search did not identify any articles that evaluated dietary ARA intake and tissue ARA as assessments of exposure. Seven of the 11 eligible articles were considered to be of low quality. No articles reported a dose-dependent positive association between an increased cerebral ischemia risk and ARA exposure. However, most studies did not assess the risk in each subtype of cerebral ischemia, thus various etiological types of cerebral ischemia risk were involved in their results.
KEY MESSAGES
We did not find a positive association between ARA exposure and cerebral ischemia risk. Eligible studies reported inconsistent findings: cerebral ischemia risk did not change or significantly decreased. We could not draw any conclusions due to the limited number of eligible high-quality studies. Further evidence from well-designed observational studies is required. Simultaneously, in order to develop effective preventive measures against cerebral ischemia, it is imperative to establish standardized definitions, nomenclatures, classifications, and diagnostic procedures.
PubMed: 26225134
DOI: 10.1159/000367588 -
European Journal of Translational... Sep 2022The aim of this study was to identify the efficacy of drug agents for pharmacological Treatment of Presbyopia. Published research papers were reviewed using the relevant...
The aim of this study was to identify the efficacy of drug agents for pharmacological Treatment of Presbyopia. Published research papers were reviewed using the relevant terms in PubMed, Science direct, Google scholar, Medline, Google patent, Ovid, Cochrane Database of Systematic Reviews, Scopus. In the initial search, 2270 records were obtained. By removing duplicate articles and all articles that did not meet the inclusion criteria or were inappropriate due to indirect relevance to the subject, 44 studies were selected. It should be noted that all studies had inclusion criteria. There are a number of topical pharmacological agents available for treating presbyopia such as FOV Tears and PresbiDrop. They consist of parasympathetic agent and non-steroidal anti-inflammatory drugs (NSAIDs), to contract the ciliary and pupil muscle and restore the accommodation. Another example of topical pharmacological agent is EV06. It is a lens-softening eye drop which can affect the rigid lens in presbyopia. Currently there is no pharmacological agent available to treat presbyopia. Although there are limited number of peer-reviewed articles available, the outcome for future agents under investigation are promising.
PubMed: 36121117
DOI: 10.4081/ejtm.2022.10781 -
Metabolomics : Official Journal of the... Aug 2023Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic... (Review)
Review
INTRODUCTION
Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC.
OBJECTIVES
To summarize and consolidate the available evidence on metabolomics and HNC in plasma/serum, saliva, and urine.
METHODS
A systematic search of experimental research was executed using PubMed and Web of Science. Available data on areas under the curve was extracted. Metabolic pathway enrichment analysis were performed to identify metabolic pathways altered in HNC. Fifty-four studies were eligible for data extraction (33 performed in plasma/serum, 15 in saliva and 6 in urine).
RESULTS
Metabolites with high discriminatory performance for detection of HNC included single metabolites and combination panels of several lysoPCs, pyroglutamate, glutamic acid, glucose, tartronic acid, arachidonic acid, norvaline, linoleic acid, propionate, acetone, acetate, choline, glutamate and others. The glucose-alanine cycle and the urea cycle were the most altered pathways in HNC, among other pathways (i.e. gluconeogenesis, glycine and serine metabolism, alanine metabolism, etc.). Specific metabolites that can potentially serve as complementary less- or non-invasive biomarkers, as well as metabolic pathways integrating the data from the available studies, are presented.
CONCLUSION
The present work highlights utility of metabolite-based biomarkers for risk assessment, early detection, and prognostication of HNC, as well as facilitates incorporation of available metabolomics studies into multi-omics data integration and big data analytics for personalized health.
Topics: Humans; Alanine; Body Fluids; Glucose; Head and Neck Neoplasms; Metabolomics
PubMed: 37644353
DOI: 10.1007/s11306-023-02038-2 -
Advances in Medical Sciences Mar 2018Rheumatoid arthritis is characterized by the production of eicosanoids, cytokines, adhesion molecules, infiltration of T and B lymphocytes in the synovium and oxygen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rheumatoid arthritis is characterized by the production of eicosanoids, cytokines, adhesion molecules, infiltration of T and B lymphocytes in the synovium and oxygen reduction accompanied by the cartilage degradation. Eicosanoids are responsible for the progressive destruction of cartilage and bone, however neither steroids, nor the non steroidal anti-inflammatory drugs (NSAIDs), cannot slow down cartilage and bone destruction providing only symptomatic improvement. The current rheumatoid arthritis treatment options include mainly the use of disease-modifying anti-rheumatic drugs, the corticosteroids, the NSAIDs and biological agents.
METHODS
PubMed, Cochrane, and Embase electronic database were used as the main sources for extracting several articles, reviews, original papers in English for further review and analysis on the implication of arachidonic acid metabolites with rheumatoid arthritis and different strategies of targeting arachidonic acid metabolites, different enzymes or receptors for improving the treatment of rheumatoid arthritis patients.
RESULTS
We first focused on the role of individual prostaglandins and leukotrienes, in the inflammatory process of arthritis, concluding with an outline of the current clinical situation of rheumatoid arthritis and novel treatment strategies targeting the arachidonic acid pathway.
CONCLUSIONS
Extended research is necessary for the development of these novel compounds targeting the eicosanoid pathway, by increasing the levels of anti-inflammatory eicosanoids (PGD,15dPGJ), by inhibiting the production of pro-inflammatory eicosanoids (PGE, LTB, PGI) involved in rheumatoid arthritis or also by developing dual compounds displaying both the COX-2 inhibitor/TP antagonist activity within a single compound.
Topics: Arthritis, Rheumatoid; Eicosanoids; Humans; Metabolic Networks and Pathways; Metabolome
PubMed: 28818745
DOI: 10.1016/j.advms.2017.06.004 -
The American Journal of Clinical... May 2023Preterm infants are at risk of long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Recent studies on high-dose DHA; n-3 LCPUFA in preterm infants suggested... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preterm infants are at risk of long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Recent studies on high-dose DHA; n-3 LCPUFA in preterm infants suggested potential positive effects on cognitive outcomes but raised concerns about some increased neonatal morbidities. These studies and recent recommendations for DHA supplementation generated controversy owing to the lack of balance between DHA and arachidonic acid (ARA; n-6 LCPUFA).
OBJECTIVES
To identify the effect of enteral supplementation of DHA, with and without ARA, on necrotizing enterocolitis (NEC) in very preterm infants.
METHODS
A systematic review of randomized and controlled trials compared enteral LCPUFAs with placebo or no supplementation in very preterm infants. We searched PubMed, Ovid-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINHAL databases from inception to July 2022. Data were extracted in duplicate using a structured proforma. A meta-analysis and metaregression with random-effects models were used. The interventions evaluated were DHA alone vs. that combined with ARA, source of DHA, dose, and supplement delivery methods. Methodological qualities and risk of bias were assessed using the Cochrane risk-of-bias tool.
RESULTS
Fifteen randomized clinical trials (RCTs) included 3963 very preterm infants with 217 cases of NEC. Supplementation with DHA alone increased NEC (2620 infants; RR: 1.56; 95% CI: 1.02, 2.39) with no evidence of heterogeneity (I = 0.0%, P = 0.46). Multiple metaregression revealed significant reduction in NEC when ARA was supplemented with DHA (aRR 0.42; 95% CI: 0.21, 0.88). The source of DHA, dose, and feeding type revealed no associations with NEC. Two RCTs supplemented high-dose DHA to lactating mothers. There was a significant increase in risk of NEC with this approach (1148 infants; RR: 1.92; 95% CI: 1.02, 3.61) with no evidence of heterogeneity (I = 0.0, P = 0.81).
CONCLUSIONS
Supplementation with DHA alone may increase risk of NEC. Concurrent supplementation with ARA needs to be considered when adding DHA to preterm infants' diet.
Topics: Infant; Infant, Newborn; Humans; Enterocolitis, Necrotizing; Infant, Premature; Dietary Supplements; Infant, Very Low Birth Weight; Infant, Premature, Diseases; Fatty Acids, Unsaturated
PubMed: 37137615
DOI: 10.1016/j.ajcnut.2023.01.007