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International Journal of Molecular... May 2021Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of...
Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of obesity because it negatively modulates the hypothalamic control of food intake due to metaflammation and lipotoxicity. The use of animal models, such as rodents, in conjunction with in vitro models of hypothalamic cells, can enhance the understanding of hypothalamic functions related to the control of energy balance, thereby providing knowledge about the impact of diet on the hypothalamus, in addition to targets for the development of new drugs that can be used in humans to decrease body weight. Recently, sphingolipids were described as having a lipotoxic effect in peripheral tissues and the central nervous system. Specifically, lipid overload, mainly from long-chain saturated fatty acids, such as palmitate, leads to excessive ceramide levels that can be sensed by the hypothalamus, triggering the dysregulation of energy balance control. However, no systematic review has been undertaken regarding studies of sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), the hypothalamus, and obesity. This review confirms that ceramides are associated with hypothalamic dysfunction in response to metaflammation, endoplasmic reticulum (ER) stress, and lipotoxicity, leading to insulin/leptin resistance. However, in contrast to ceramide, S1P appears to be a central satiety factor in the hypothalamus. Thus, our work describes current evidence related to sphingolipids and their role in hypothalamic energy balance control. Hypothetically, the manipulation of sphingolipid levels could be useful in enabling clinicians to treat obesity, particularly by decreasing ceramide levels and the inflammation/endoplasmic reticulum stress induced in response to overfeeding with saturated fatty acids.
Topics: Animals; Ceramides; Diet, High-Fat; Endoplasmic Reticulum Stress; Energy Metabolism; Fatty Acids; Humans; Hypothalamus; Insulin Resistance; Leptin; Lysophospholipids; Obesity; Signal Transduction; Sphingolipids; Sphingosine
PubMed: 34069652
DOI: 10.3390/ijms22105357 -
Cells May 2021Fibroblastic reticular cells (FRCs), usually found and isolated from the T cell zone of lymph nodes, have recently been described as much more than simple structural...
Fibroblastic reticular cells (FRCs), usually found and isolated from the T cell zone of lymph nodes, have recently been described as much more than simple structural cells. Originally, these cells were described to form a conduit system called the "reticular fiber network" and for being responsible for transferring the lymph fluid drained from tissues through afferent lymphatic vessels to the T cell zone. However, nowadays, these cells are described as being capable of secreting several cytokines and chemokines and possessing the ability to interfere with the immune response, improving it, and also controlling lymphocyte proliferation. Here, we performed a systematic review of the several methods employed to investigate the mechanisms used by fibroblastic reticular cells to control the immune response, as well as their ability in determining the fate of T cells. We searched articles indexed and published in the last five years, between 2016 and 2020, in PubMed, Scopus, and Cochrane, following the PRISMA guidelines. We found 175 articles published in the literature using our searching strategies, but only 24 articles fulfilled our inclusion criteria and are discussed here. Other articles important in the built knowledge of FRCs were included in the introduction and discussion. The studies selected for this review used different strategies in order to access the contribution of FRCs to different mechanisms involved in the immune response: 21% evaluated viral infection in this context, 13% used a model of autoimmunity, 8% used a model of GvHD or cancer, 4% used a model of Ischemic-reperfusion injury (IRI). Another four studies just targeted a particular signaling pathway, such as MHC II expression, FRC microvesicles, FRC secretion of IL-15, FRC network, or ablation of the lysophosphatidic acid (LPA)-producing ectoenzyme autotaxin. In conclusion, our review shows the strategies used by several studies to isolate and culture fibroblastic reticular cells, the models chosen by each one, and dissects their main findings and implications in homeostasis and disease.
Topics: Animals; Autoimmunity; Cell Proliferation; Cytokines; Fibroblasts; Homeostasis; Humans; Immunophenotyping; Lymph; Lymph Nodes; Lymphatic Vessels; Lymphocytes; Lysophospholipids; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Neoplasms; Reticulin; T-Lymphocytes
PubMed: 34068712
DOI: 10.3390/cells10051150 -
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 -
Journal of Alternative and... Apr 2021To examine the evidence for efficacy of phosphatidylserine for symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Medline, Cochrane Library, and... (Meta-Analysis)
Meta-Analysis
To examine the evidence for efficacy of phosphatidylserine for symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Medline, Cochrane Library, and ClinicalTrials.gov were searched from inception through August 2020. Studies of any design that assessed phosphatidylserine supplementation for children aged ≤18 years with a diagnosis of ADHD were included in the systematic review; only randomized clinical trials were included in the meta-analysis. Standardized mean differences and 95% confidence intervals (CIs) were calculated, and the heterogeneity of the studies was estimated using . The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Four studies met the inclusion criteria for the narrative review ( = 344) and three for the meta-analysis ( = 216). Results of the meta-analysis showed a statistically significant effect of 200-300 mg/day of phosphatidylserine on symptoms of inattention relative to placebo (effect size [ES] 0.36; 95% CI: 0.07 to 0.64; = 0.01). The effects of phosphatidylserine on overall symptoms of ADHD (ES 0.76; 95% CI: -0.07 to 1.60; = 0.07) and hyperactivity-impulsivity (ES 0.24; 95% CI: -0.04 to 0.53; = 0.09) were not statistically significant. Preliminary evidence suggests that phosphatidylserine may be effective for reducing symptoms of inattention in children with ADHD, although the quality of the evidence is low and additional research in this area is warranted.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Humans; Integrative Medicine; Phosphatidylserines; Randomized Controlled Trials as Topic
PubMed: 33539192
DOI: 10.1089/acm.2020.0432 -
Talanta Feb 2021Stimulated by the increased recognition of phosphatidylethanol (PEth) as sensitive direct marker of alcohol intake, the Ghent University's Laboratory of Toxicology and...
BACKGROUND
Stimulated by the increased recognition of phosphatidylethanol (PEth) as sensitive direct marker of alcohol intake, the Ghent University's Laboratory of Toxicology and the National Institute of Criminalistics and Criminology combined their efforts to develop a quantitative method. To facilitate implementation the focus was on the use of a sampling technique which allows quick and easy blood collection, without the need of dedicated personnel at any place/any time. In the meantime the cooperation of the two labs should also allow to initiate a Belgian network of laboratories capable of quantifying PEth.
METHODS
Dried blood microsamples were collected via volumetric absorptive microsampling (VAMS). PEth 16:0/18:1 was quantified after liquid-liquid extraction using two independent isotope dilution - liquid chromatography - tandem mass spectrometry methods. A systematic review of the entire process at both sites was performed before the final method comparison using samples from 59 routine toxicology cases collected within a one-year time interval.
RESULTS
Initial differences between both laboratories were solved by focusing on important methodological aspects: (i) trueness verification of the calibration protocol focusing on the primary material, preparation of the stock solutions and adequate equilibration of calibrators and QCs, and (ii) verification of comparability of results obtained with different m/z transitions. Several of these aspects could only be verified by critically assessing spiked and native samples. After a final validation good average comparability of the two methods was observed. The average bias was -0.4%, with 85% of the differences within 20%. Moreover, the methods proved to be reproducible and robust within a one-year time interval.
CONCLUSION
This study is the first to develop a quantitative volumetric absorptive microsampling based method for PEth measurements, in addition it is the first to perform a systematic comparison of PEth measurements between two laboratories. From the discussion on the encountered pitfalls it is clear that also on a global scale, more efforts are needed to improve interlaboratory agreement.
Topics: Chromatography, Liquid; Dried Blood Spot Testing; Glycerophospholipids; Humans; Tandem Mass Spectrometry
PubMed: 33303146
DOI: 10.1016/j.talanta.2020.121694 -
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 -
Thrombosis and Haemostasis Apr 2020The aim of the study is to perform a systematic review on the recent available evidence on antiphosphatidylserine/prothrombin (aPS/PT) antibodies and their...
OBJECTIVE
The aim of the study is to perform a systematic review on the recent available evidence on antiphosphatidylserine/prothrombin (aPS/PT) antibodies and their association with clinical manifestations of the antiphospholipid syndrome (APS).
METHODS
A detailed literature search was applied to Ovid MEDLINE, In-Process and Other Non-Indexed Citation 2012 to present and to abstract from EULAR and ACR/ARHP Annual Meetings (2012-2019).
RESULTS
Data from 2,901 patients, 587 diseases controls and 559 healthy controls included in 15 retrieved studies was analyzed. The patient population included 1,219 patients classified as APS according to the Sidney criteria, 285 patients with isolated persistently positive antiphospholipid antibodies (aPL) and 1,397 patients with a clinical suspicion of APS. Twelve studies, including 1,888 patients, analyzed the association between aPS/PT antibodies and thrombosis. We observed a statistically significant association between aPS/PT IgG/IgM positivity and thrombotic events (mean odds ratio [OR]: 6.8 [95% CI: 3.18-16.4], < 0.05), confirmed when analyzing aPS/PT IgG (mean OR: 6.7 [95% CI: 3.04-21.6], < 0.05) and aPS/PT IgM (mean OR: 4.35 [95% CI: 1.54-17.77], 0.05) separately. Seven studies, including 1,388 patients, evaluated the association between aPS/PT antibodies and PM. When pooled together, we found a statistically significant association between any PM and aPS/PT IgG/IgM positivity (mean OR: 10.6 [95% CI: 3.54-35.38], 0.05), particularly aPS/PT IgG positivity (mean OR: 6.7 [95% CI: 3.04-21.6], 0.05).
CONCLUSION
Our results highlight the strong association between aPS/PT and the clinical manifestations of APS. With the available level of evidence, aPS/PT testing can be considered as a robust test applicable in the investigation of patients suspected for APS, also beyond the research settings.
Topics: Animals; Antiphospholipid Syndrome; Autoantibodies; Humans; Phosphatidylserines; Prothrombin; Seroepidemiologic Studies; Thrombosis
PubMed: 32185783
DOI: 10.1055/s-0040-1705115 -
The British Journal of Nutrition Dec 2019Little is known about the association between dietary choline intake and mortality. We evaluated the link between choline consumption and overall as well as... (Meta-Analysis)
Meta-Analysis
Dietary choline is positively related to overall and cause-specific mortality: results from individuals of the National Health and Nutrition Examination Survey and pooling prospective data.
Little is known about the association between dietary choline intake and mortality. We evaluated the link between choline consumption and overall as well as cause-specific mortality by using both individual data and pooling prospective studies by meta-analysis and systematic review. Furthermore, adjusted means of cardiometabolic risk factors across choline intake quartiles were calculated. Data from the National Health and Nutrition Examination Survey (1999-2010) were collected. Adjusted Cox regression was performed to determine the risk ratio (RR) and 95 % CI, as well as random-effects models and generic inverse variance methods to synthesise quantitative and pooling data, followed by a leave-one-out method for sensitivity analysis. After adjustments, we found that individuals consuming more choline had worse lipid profile and glucose homeostasis, but lower C-reactive protein levels (P < 0·001 for all comparisons) with no significant differences in anthropometric parameters and blood pressure. Multivariable Cox regression models revealed that individuals in the highest quartile (Q4) of choline consumption had a greater risk of total (23 %), CVD (33 %) and stroke (30 %) mortality compared with the first quartile (Q1) (P < 0·001 for all comparison). These results were confirmed in a meta-analysis, showing that choline intake was positively and significantly associated with overall (RR 1·12, 95 % CI 1·08, 1·17, I2 = 2·9) and CVD (RR 1·28, 95 % CI 1·17, 1·39, I2 = 9·6) mortality risk. In contrast, the positive association between choline consumption and stroke mortality became non-significant (RR 1·18, 95 % CI 0·97, 1·43, P = 0·092, I2 = 1·1). Our findings shed light on the potential adverse effects of choline intake on selected cardiometabolic risk factors and mortality risk.
Topics: Adult; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Choline; Diet; Ethnicity; Female; Glycerophospholipids; Humans; Lipids; Male; Middle Aged; Mortality; Nutrition Surveys; Odds Ratio; Socioeconomic Factors; Stroke
PubMed: 31288869
DOI: 10.1017/S0007114519001065 -
Critical Care (London, England) Feb 2019With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in pulmonary disease diagnosis. We aimed to review and summarize lung fluid biomarkers associated with acute respiratory distress syndrome diagnosis and mortality.
METHODS
After searching PubMed, Embase, Web of Science, and the Cochrane Library for articles published prior to January 11, 2018, we performed a meta-analysis on biomarkers for acute respiratory distress syndrome diagnosis in at-risk patients and those related to disease mortality. From the included studies, we then extracted the mean and standard deviation of the biomarker concentrations measured in the lung fluid, acute respiratory distress syndrome etiologies, sample size, demographic variables, diagnostic criteria, mortality, and protocol for obtaining the lung fluid. The effect size was measured by the ratio of means, which was then synthesized by the inverse-variance method using its natural logarithm form and transformed to obtain a pooled ratio and 95% confidence interval.
RESULTS
In total, 1156 articles were identified, and 49 studies were included. Increases in total phospholipases A2 activity, total protein, albumin, plasminogen activator inhibitor-1, soluble receptor for advanced glycation end products, and platelet activating factor-acetyl choline were most strongly associated with acute respiratory distress syndrome diagnosis. As for biomarkers associated with acute respiratory distress syndrome mortality, interleukin-1β, interleukin-6, interleukin-8, Kerbs von Lungren-6, and plasminogen activator inhibitor-1 were significantly increased in the lung fluid of patients who died. Decreased levels of Club cell protein and matrix metalloproteinases-9 were associated with increased odds for acute respiratory distress syndrome diagnosis, whereas decreased levels of Club cell protein and interleukin-2 were associated with increased odds for acute respiratory distress syndrome mortality.
CONCLUSIONS
This meta-analysis provides a ranking system for lung fluid biomarkers, according to their association with diagnosis or mortality of acute respiratory distress syndrome. The performance of biomarkers among studies shown in this article may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.
Topics: Antigens, Human Platelet; Biomarkers; Bronchoalveolar Lavage Fluid; Hepatocyte Growth Factor; Humans; Interleukin-8; Lung; Plasminogen Activator Inhibitor 1; Platelet Activating Factor; Receptor for Advanced Glycation End Products; Respiratory Distress Syndrome
PubMed: 30755248
DOI: 10.1186/s13054-019-2336-6 -
Scientific Reports Jan 2019An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested... (Meta-Analysis)
Meta-Analysis
An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested using different models of toxic demyelination such as cuprizone, ethidium bromide, or lysolecithin and some of the therapies already entered clinical trials. However, keeping track on all these possible new therapies and their efficacy has become difficult with the increasing number of studies. In this study, we aimed at summarizing the current evidence on such therapies through a systematic review and at providing an estimate of the effects of tested interventions by a meta-analysis. We show that 88 different therapies have been pre-clinically tested for remyelination. 25 of them (28%) entered clinical trials. Our meta-analysis also identifies 16 promising therapies which did not enter a clinical trial for MS so far, among them Pigment epithelium-derived factor, Plateled derived growth factor, and Tocopherol derivate TFA-12.We also show that failure in bench to bedside translation from certain therapies may in part be attributable to poor study quality. By addressing these problems, clinical translation might be smoother and possibly animal numbers could be reduced.
Topics: Animals; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Ethidium; Eye Proteins; Lysophosphatidylcholines; Mice; Multiple Sclerosis; Myelin Sheath; Nerve Growth Factors; Oligodendrocyte Precursor Cells; Oligodendroglia; Platelet-Derived Growth Factor; Remyelination; Serpins; Tocopherols
PubMed: 30696832
DOI: 10.1038/s41598-018-35734-4