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Frontiers in Immunology 2021Psoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of autoimmune diseases. However, there is currently a lack of comprehensive evidence of the effectiveness of S1P on psoriasis.
OBJECTIVE
To assess the efficacy and possible mechanism of S1P and its signal modulators in the treatment of psoriasis-like dermatitis.
METHODS
Six databases were searched through May 8, 2021, for studies reporting S1P and its signal modulators. Two reviewers independently extracted information from the enrolled studies. Methodological quality was assessed using SYRCLE's risk of bias tool. RevMan 5.3 software was used to analyze the data. For clinical studies, the Psoriasis Area and Severity Index score were the main outcomes. For preclinical studies, we clarified the role of S1P and its regulators in psoriasis in terms of phenotype and mechanism.
RESULTS
One randomized double-blind placebo-controlled trial and nine animal studies were included in this study. The pooled results showed that compared with control treatment, S1P receptor agonists [mean difference (MD): -6.80; 95% confidence interval (CI): -8.23 to -5.38; p<0.00001], and sphingosine kinase 2 inhibitors (MD: -0.95; 95% CI: -1.26 to -0.65; p<0.00001) alleviated psoriasis-like dermatitis in mice. The mechanism of S1P receptor agonists in treating psoriasis might be related to a decrease in the number of white blood cells, topical lymph node weight, interleukin-23 mRNA levels, and percentage of CD3 T cells (p<0.05). Sphingosine kinase 2 inhibitors ameliorated psoriasis in mice, possibly by reducing spleen weight and cell numbers (p<0.05).
CONCLUSIONS
S1P receptor agonists and sphingosine kinase 2 inhibitors could be potential methods for treating psoriasis by decreasing immune responses and inflammatory factors.
Topics: Animals; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Lysophospholipids; Mice; Phosphotransferases (Alcohol Group Acceptor); Psoriasis; Randomized Controlled Trials as Topic; Receptors, Lysosphingolipid; Software; Sphingosine
PubMed: 34992595
DOI: 10.3389/fimmu.2021.759276 -
Nutrition Reviews May 2022Atherosclerosis is a disease of chronic inflammation. Recent research has identified 2 novel inflammatory biomarkers: platelet-activating factor (PAF) and...
CONTEXT
Atherosclerosis is a disease of chronic inflammation. Recent research has identified 2 novel inflammatory biomarkers: platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Diet has been proposed as a mediator of inflammation, but to date, the focus for these novel biomarkers has been on individual foods and nutrients rather than overall dietary patterns.
OBJECTIVE
To systematically review the literature on the association between dietary patterns and PAF and Lp-PLA2.
DATA SOURCES
The PubMed, Embase, CINAHL, and Cochrane CENTRAL literature databases were searched.
DATA ANALYSIS
Study quality was evaluated using the Quality Criteria Checklist. Sixteen studies (n = 4 observational and n = 12 interventional) were included and assessed for associations between dietary patterns and PAF and Lp-PLA2.
CONCLUSION
Study quality varied from neutral (n = 10) to positive (n = 6). Mediterranean, heart healthy, and vegetarian dietary patterns were associated with improved levels of PAF and Lp-PLA2. Conversely, Western dietary patterns were less favorable. A range of well-established, healthier dietary patterns may lower inflammation and the risk of atherosclerosis. More well-designed studies are needed to confirm these findings and identify other dietary patterns that improve inflammation.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Atherosclerosis; Biomarkers; Humans; Inflammation; Platelet Activating Factor
PubMed: 34651191
DOI: 10.1093/nutrit/nuab051 -
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 -
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 -
Cancer Medicine Feb 2023Cutaneous adverse effects (AEs) are common following the phosphoinositide-3-kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K... (Meta-Analysis)
Meta-Analysis Review
Risk of cutaneous adverse events in cancer patients treated with phosphatidylinositol-3-kinase inhibitors: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Cutaneous adverse effects (AEs) are common following the phosphoinositide-3-kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K inhibitor-related cutaneous AEs.
METHODS
The protocol was submitted to the PROSPERO registry. We searched ClinicalTrials.gov and international databases up to July 29, 2022. Meta-analysis was conducted by using risk ratios (RRs) with 95% confidence intervals (CIs).
RESULTS
Fourteen randomized controlled trials (RCTs) comprising 3877 patients were analyzed in this study. Compared with control arms, PI3K inhibitors showed a significant increase in the risk of all-grade rash, high-grade rash, and serious rash events (RR 2.29, 95% CI 1.58-3.31, p < 0.00001; RR 9.34, 95% CI 4.21-20.69, p < 0.00001; RR 5.11, 95% CI 2.11-12.36, p = 0.0003). The overall incidences of all-grade rash and high-grade rash were 26.2% (592/2257) and 4.4% (66/1487). Subgroup analyses of all-grade rash according to cancer types and PI3K inhibitor assignations identified the significant associations. PI3K inhibitors also significantly increased the risk of pruritus and dry skin (RR 1.63, 95% CI 1.14-2.33, p = 0.007; RR 3.34, 95% CI 2.30-4.85, p < 0.00001), with incidences of 13.4% (284/2115) and 9.8% (141/1436) in the treatment group.
CONCLUSION
There is a significantly increased risk of some cutaneous AEs in patients using PI3K inhibitors. Advance intervention is recommended in case of severe and life-threatening events. Further research is required to investigate the risk factors and pathogenesis.
Topics: Humans; Randomized Controlled Trials as Topic; Neoplasms; Phosphoinositide-3 Kinase Inhibitors; Exanthema; Phosphatidylinositol 3-Kinases; Phosphatidylinositols
PubMed: 35986570
DOI: 10.1002/cam4.5153 -
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 -
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 -
BMC Cancer Sep 2022Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC. METHODS: Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies.
RESULTS
The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I = 35%) and shorter median OS (-8.4 [-13.4, -3.5], I = 58%, N = 1,545). Findings were similar for PFS rates at 6 months (odds ratio [95% CI]: 0.74 [0.59, 0.94], I = 42%, N = 3,160) and 12 months (0.76 [0.59, 0.99], I = 42%, N = 2,468) and directionally consistent but not statistically significant at 18 months (N = 1,726).
CONCLUSIONS
Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Disease-Free Survival; Female; Humans; Mutation; Phosphatidylinositol 3-Kinases; Phosphatidylinositols; Receptor, ErbB-2
PubMed: 36131248
DOI: 10.1186/s12885-022-10078-5 -
Frontiers in Endocrinology 2023Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that...
Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that present mainly as hyperglycemia. Here, we present two case reports of diabetes mellitus caused by the use of tremelimumab and apalutamide, respectively, in cancer treatment, and a comprehensive, comparative review of the literature on these forms of diabetes. Case 1 presented with diabetic ketoacidosis and was diagnosed with ICI-related diabetes mellitus and treated with insulin. Case 2 was diagnosed with PI3Ki-related diabetes mellitus, and her blood glucose level returned to normal with the use of metformin and dapagliflozin. We systematically searched the PubMed database for articles on ICI- and PI3Ki-related diabetes mellitus and characterized the differences in clinical features and treatment between these two forms of diabetes.
Topics: Female; Humans; Antineoplastic Agents; Diabetes Mellitus; Diabetic Ketoacidosis; Hyperglycemia; Immune Checkpoint Inhibitors; Phosphatidylinositols
PubMed: 37732122
DOI: 10.3389/fendo.2023.1236946