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Cardiovascular Drugs and Therapy Feb 2021Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists....
BACKGROUND
Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists. Specifically, new drugs are needed for non-responding or statin-intolerant subjects or patients considered at very high risk for cardiovascular events even though are already on treatment with the best standard of care.
RESULTS AND CONCLUSIONS
Besides, genetic and epidemiological studies and Mendelian randomization analyses have strengthened the linear correlation between the concentration of low-density lipoprotein cholesterol (LDL-C) and the incidence of cardiovascular events and highlighted various novel therapeutic targets. This review describes the novel strategies to reduce the levels of LDL-C, non-HDL-C, triglyceride, apolipoprotein B, and Lp(a), focusing on those developed using biotechnology-based strategies.
Topics: Antibodies, Monoclonal, Humanized; Apolipoproteins B; Cholesterol, LDL; Clinical Trials as Topic; Dyslipidemias; Genetic Therapy; Humans; Hypolipidemic Agents; Lysophospholipids; Oligonucleotides, Antisense; RNA, Small Interfering; Triglycerides
PubMed: 32519066
DOI: 10.1007/s10557-020-07017-6 -
International Journal of Molecular... Jul 2023The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are... (Review)
Review
The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are influenced by memory bias and under-reporting. In recent years, phosphatidylethanol (PEth) in blood has emerged as a marker of unhealthy alcohol use. This systematic review aims to investigate the molecular characteristics of PEth and summarize the last ten years of published literature and its use compared to structured questionnaires. A systematic search was performed, adhering to PRISMA guidelines, through "MeSH" and "free-text" protocols in the databases PubMed, SCOPUS, and Web of Science. The inclusion criteria were as follows: PEth was used for detecting unhealthy alcohol consumption in the general population and quantified in blood through liquid chromatography coupled to mass spectrometry, with full texts in the English language. Quality assessment was performed using the JBI critical appraisal checklist. Twelve papers were included (0.79% of total retrieved records), comprising nine cross-sectional studies and three cohort studies. All studies stratified alcohol exposure and quantified PEth 16:0/18:1 through liquid chromatography coupled to mass spectrometry (LC-MS) in liquid blood or dried blood spots (DBS) with lower limits of quantitation (LLOQ) ranging from 1.7 ng/mL to 20 ng/mL. A correlation between blood PEth level and the amount of alcohol ingested in the previous two weeks was generally observed. PEth interpretative cut-offs varied greatly among the included records, ranging from 4.2 ng/mL to 250 ng/mL, with sensitivity and specificity in the ranges of 58-100% and 64-100%, respectively. Although the biomarker seems promising, further research elucidating the variability in PEth formation and degradation, as well as the molecular mechanisms behind that variability, are necessary.
Topics: Humans; Alcoholism; Cross-Sectional Studies; Alcohol Drinking; Glycerophospholipids; Ethanol; Biomarkers
PubMed: 37569551
DOI: 10.3390/ijms241512175 -
Journal of Dairy Science Jan 2023Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species... (Review)
Review
Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models.
Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species associated with dairy consumption mediate this relationship. This scoping review aimed to identify the existing literature in animal and human trials investigating the impact of dairy products, including milk, yogurt, and cheese as well as dairy-derived PL supplementation on PL and its species in the circulation, summarizing the characteristics of these studies and identifying research gaps. A systematic search was conducted across 3 databases (PubMed, Scopus, and Web of Science) in March 2021. Of 2,427 identified references, 15 studies (7 humans and 8 animal studies) met the eligibility criteria and were included in the final narrative synthesis. The evidence base was heterogeneous, involving a variety of clinical and preclinical studies, metabolically healthy or obese/diabetic participants or animal models, and displayed mixed findings. Circulating postprandial concentrations of total PL were elevated acutely but unchanged after longer intervention with dairy products. The PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL, which may be related to increased fecal excretion; however, certain phosphatidylcholine (PC) or lysophosphatidylcholine species were increased in circulation by interventions. These include several PC species with 32 to 38 total carbons in addition to the dairy biomarkers C15:0 and C17:0. The results of this scoping review demonstrate a small body of literature indicating that dairy products can influence blood concentrations of PC and lysophosphatidylcholine species in both rodents and humans without alteration of total PL and PC. There is a lack of well-designed trials in humans and animals that explore the potential differences between individual dairy foods on PL species. In addition, trials to understand the bioactive properties of PC and lysophosphatidylcholine species on cardiometabolic risk are needed.
Topics: Animals; Humans; Dairy Products; Diabetes Mellitus, Type 2; Diet; Liver; Lysophosphatidylcholines; Milk; Models, Animal; Phosphatidylcholines; Students; Yogurt
PubMed: 36400621
DOI: 10.3168/jds.2022-21938 -
Advances in Nutrition (Bethesda, Md.) Feb 2024Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating... (Review)
Review
The Relationship of Circulating Choline and Choline-Related Metabolite Levels with Health Outcomes: A Scoping Review of Genome-Wide Association Studies and Mendelian Randomization Studies.
Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating choline metabolites can help identify new determinants of choline metabolism, requirements, and their link to disease endpoints. We conducted a scoping review to identify studies assessing the association of genetic polymorphisms on circulating choline and choline-related metabolite concentrations and subsequent associations with health outcomes. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement scoping review extension. Literature was searched to September 28, 2022, in 4 databases: Embase, MEDLINE, Web of Science, and the Biological Science Index. Studies of any duration in humans were considered. Any genome-wide association study (GWAS) investigating genetic variant associations with circulating choline and/or choline-related metabolites and any Mendelian randomization (MR) study investigating the association of genetically predicted circulating choline and/or choline-related metabolites with any health outcome were considered. Qualitative evidence is presented in summary tables. From 1248 total reviewed articles, 53 were included (GWAS = 27; MR = 26). Forty-two circulating choline-related metabolites were tested in association with genetic variants in GWAS studies, primarily trimethylamine N-oxide, betaine, sphingomyelins, lysophosphatidylcholines, and phosphatidylcholines. MR studies investigated associations between 52 total unique choline metabolites and 66 unique health outcomes. Of these, 47 significant associations were reported between 16 metabolites (primarily choline, lysophosphatidylcholines, phosphatidylcholines, betaine, and sphingomyelins) and 27 health outcomes including cancer, cardiovascular, metabolic, bone, and brain-related outcomes. Some articles reported significant associations between multiple choline types and the same health outcome. Genetically predicted circulating choline and choline-related metabolite concentrations are associated with a wide variety of health outcomes. Further research is needed to assess how genetic variability influences choline metabolism and whether individuals with lower genetically predicted circulating choline and choline-related metabolite concentrations would benefit from a dietary intervention or supplementation.
Topics: Humans; Choline; Betaine; Genome-Wide Association Study; Sphingomyelins; Mendelian Randomization Analysis; Lysophosphatidylcholines; Phosphatidylcholines; Polymorphism, Single Nucleotide
PubMed: 38128611
DOI: 10.1016/j.advnut.2023.100164 -
Lipids in Health and Disease May 2024Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction,... (Review)
Review
Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography-tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice.
Topics: Humans; Prognosis; Neoplasms; Lipidomics; Biomarkers, Tumor; Mass Spectrometry; Female; Lipids; Male; Breast Neoplasms; Prostatic Neoplasms; Lysophospholipids; Colorectal Neoplasms
PubMed: 38796445
DOI: 10.1186/s12944-024-02121-0 -
International Journal of Molecular... Nov 2017The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years,... (Review)
Review
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.
Topics: Adult; Brain Neoplasms; Cell Movement; Disease Progression; GTP-Binding Proteins; Glioblastoma; Humans; Lysophospholipids; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Receptors, Lysosphingolipid; Sphingosine
PubMed: 29149079
DOI: 10.3390/ijms18112448 -
International Journal of Molecular... Jan 2024Lipids are a large group of natural compounds, together with proteins and carbohydrates, and are essential for various processes in the body. After death, the organism's... (Review)
Review
Lipids are a large group of natural compounds, together with proteins and carbohydrates, and are essential for various processes in the body. After death, the organism's tissues undergo a series of reactions that generate changes in some molecules, including lipids. This means that determining the lipid change profile can be beneficial in estimating the postmortem interval (PMI). These changes can also help determine burial sites and advance the localization of graves. The aim was to explore and analyze the decomposition process of corpses, focusing on the transformation of lipids, especially triglycerides (TGs) and fatty acids (FAs), and the possible application of these compounds as markers to estimate PMI and detect burial sites. A systematic review of 24 scientific articles from the last 23 years (2000-2023) was conducted. The results show that membrane glycerophospholipids (such as phosphatidylcholine and phosphatidylglycerol, among others) are the most studied, and the most promising results are obtained, with decreasing patterns as PMI varies. Fatty acids (FAs) are also identified as potential biomarkers owing to the variations in their postmortem concentration. An increase in saturated fatty acids (SFAs), such as stearic acid and palmitic acid, and a decrease in unsaturated fatty acids (UFAs), such as oleic acid and linoleic acid, were observed. The importance of intrinsic and extrinsic factors in decomposition is also observed. Finally, as for the burial sites, the presence of fatty acids and some sterols in burial areas of animal and human remains can be verified. In conclusion, glycerophospholipids and fatty acids are good markers for estimating PMI. It has been observed that there are still no equations for estimating the PMI that can be applied to forensic practice, as intrinsic and extrinsic factors are seen to play a vital role in the decomposition process. As for determining burial sites, the importance of soil and textile samples has been demonstrated, showing a direct relationship between saturated fatty acids, hydroxy fatty acids, and some sterols with decomposing remains.
Topics: Animals; Humans; Lipidomics; Fatty Acids; Cadaver; Phytosterols; Sterols; Glycerophospholipids
PubMed: 38256058
DOI: 10.3390/ijms25020984 -
Thrombosis Research Jun 2022Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) and thrombotic events. The association of... (Meta-Analysis)
Meta-Analysis Review
Prevalence of aPhosphatidylserine/prothrombin antibodies and association with antiphospholipid antibody profiles in patients with antiphospholipid syndrome: A systematic review and meta-analysis.
BACKGROUND
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) and thrombotic events. The association of aPLs with thrombotic events depends on the number of positive tests. Besides the three classical tests to classify APS, phosphatidylserine/prothrombin complex autoantibodies (aPS/PT) are increasingly used to better define this condition. The aim of this systematic review was to evaluate the prevalence of aPS/PT in general and according to antiphospholipid antibody profiles in patients with APS.
METHODS
A systematic search of PubMed, Web of Science, and the Cochrane Library from January 1990 to September 2021 was carried out according to PRISMA guidelines. Proportions and 95% confidence intervals (CIs) were calculated using random-effects model. Publication biases were evaluated via visualization of funnel plots along with Egger's and Begg's tests.
RESULTS
Twenty-one articles about the prevalence of aPS/PT in 1853 patients with APS were deemed eligible and analyzed according to the inclusion criteria. Pooled prevalence of aPS/PT IgG alone, IgM alone, and IgG/M were 50.0%, 45.0%, and 65.0%, respectively. No significant publication bias was detected from funnel plots or Egger's and Begg's tests. When the prevalence of aPS/PT was calculated in homogeneous aPLs, a much higher rate of pooled prevalence of aPS/PT IgG/M in patients positive for Lupus Anticoagulant (84.5%) and in those with triple positivity (83.4%) was found.
CONCLUSIONS
These data show a high rate of aPS/PT positivity in patients with APS (especially in those positive for LAC) but further studies are needed to ascertain whether this test might be useful in the laboratory classification criteria of APS.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Humans; Immunoglobulin G; Phosphatidylserines; Prevalence; Prothrombin; Thrombosis
PubMed: 35526513
DOI: 10.1016/j.thromres.2022.04.021 -
European Journal of Obstetrics,... Jun 2017Accurate and early identification of women at risk from alcohol consumption during pregnancy allows education and support programmes to be targeted at those most in... (Review)
Review
Accurate and early identification of women at risk from alcohol consumption during pregnancy allows education and support programmes to be targeted at those most in need. We aimed to conduct a systematic review to compare the efficacy of blood analysis and maternal self-report in detecting at risk women during pregnancy. This review investigated diagnostic accuracy. We searched four databases (Medline, Embase, Psychinfo and CINAHL) for relevant articles and conducted hand searches of recent issues of key journals in the field. No restriction was placed on inclusion in terms of publication date or language. Studies were deemed eligible if they were original research and included a direct comparison of the results of blood biomarker analysis and self-reported alcohol use for the detection of alcohol consumption in pregnant women. Quality appraisal of included studies was conducted using the QUADAS II tool. Eight studies met the inclusion criteria. Gamma-glutamyltransferase (GGT) was investigated in five studies, mean corpuscular volume (MCV) and phosphatidylethanol (PEth) in three studies and carbohydrate deficient transferrin (CDT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and whole blood associated acetaldehyde assay (WBAA) were each investigated in two studies. Although all of the studies were rated of good methodological quality, none of the biomarkers had both high sensitivity and specificity when compared to self-report. There was some evidence that a combination of biomarkers, or combining biomarkers with self-report, increases accuracy. In summary, the blood biomarkers examined were of limited use in screening for low and moderate alcohol consumption in pregnancy when compared to self-report. However, certain biomarkers, such and CDT and PEth may complement self-report and help improve the accuracy of diagnosis.
Topics: Alanine Transaminase; Alcohol Drinking; Aspartate Aminotransferases; Biomarkers; Erythrocyte Indices; Female; Glycerophospholipids; Humans; MEDLINE; Pregnancy; Self Report; Sensitivity and Specificity; Transferrin; gamma-Glutamyltransferase
PubMed: 28426943
DOI: 10.1016/j.ejogrb.2017.04.005 -
Ageing Research Reviews Jul 2021Aging affects the serum levels of various metabolites which may be involved in the pathogenesis of chronic diseases. The aim of this review article is to summarize the...
BACKGROUND
Aging affects the serum levels of various metabolites which may be involved in the pathogenesis of chronic diseases. The aim of this review article is to summarize the relationship between aging and alterations in the plasma phospholipids and sphingomyelins.
METHODS
PRISMA guidelines were employed during all steps. MEDLINE (PubMed), Scopus, Embase and Web of Sciences databases and Google Scholar were searched up to October 2020. Cohort studies investigating the relationship between aging and within-person changes in sphingomyelin (SM), phosphatidyl choline (PC), lyso PC (LPC) and phosphatidyl ethanolamine (PE) were included. Newcastle-Ottawa scale was used to assess the quality of included studies.
RESULTS
A total of 1425 studies were identified. After removing 610 duplicates and 723 irrelevant studies, full texts of 92 articles were evaluated. Of these 92, 6 studies (including data from 7 independent cohorts) met the inclusion criteria and are included in this review. All study populations were healthy and included both men and women. Results by sex were reported in 3 cohorts for PC, 5 cohorts for LPC, 3 cohorts for SM, and only 1 cohort for PE. In men, PC, SM, PE and LPC decreased with aging, although results for LPC were inconsistent. In women, LPC, SM, and PE increased age, whereas changes in PC were inconsistent.
CONCLUSION
Within-person serum levels of phospholipids and sphingomyelins, decrease during aging in men and increase in women. Notably, however, there were some inconsistencies across studies of LPC in men and of PC in women.
Topics: Aging; Female; Humans; Longitudinal Studies; Male; Phosphatidylcholines; Phospholipids; Sphingomyelins
PubMed: 33839333
DOI: 10.1016/j.arr.2021.101340