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Diabetes, Obesity & Metabolism Aug 2021To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation... (Meta-Analysis)
Meta-Analysis
AIM
To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes.
METHODS
Medline, Embase and the Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation: C-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNFα), plasminogen activator inhibitor-1, interleukin-6, leptin; and of oxidative stress: malondialdehyde (MDA); 8-iso-prostaglandin F2α; and 8-hydroxy-2'-deoxyguanosine (8-OHdG).
RESULTS
We included 40 eligible RCTs (n = 6749) with a median follow-up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m and diabetes duration 7.46 years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference -0.54 mg/L [-0.75, -0.34]; standard mean difference [SMD] -0.39 [-0.62, -0.15]; SMD -0.84 [-1.61, -0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not.
CONCLUSIONS
There is strong evidence supporting clinically relevant anti-inflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and the development of medications seeking to target the cardioprotective properties of GLP-1RAs.
Topics: Biomarkers; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Inflammation; Male; Middle Aged; Oxidative Stress; Randomized Controlled Trials as Topic
PubMed: 33830637
DOI: 10.1111/dom.14399 -
Journal of Medicinal Food Nov 2023The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines,... (Review)
Review
The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines, of the articles found in the past 11 years on the gastroprotective role of fruit extracts in gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). Scientific articles published between 2010 and 2020 were included in this systematic review, including and models, to define the gastroprotective role of fruit extracts. Studies were selected by Rayyan using PubMed, Web of Science, Scopus, and Science Direct databases. The keywords for the search strategy were: "gastric injury," "gastric ulcer," "fruit," "indomethacin," and "aspirin." Twenty-two articles with animal models of gastric ulcers were included. The NSAIDs used were aspirin and indomethacin. To know the damage caused by these, the ulceration index and biomarkers, such as aggressive/defensive factors involved in the gastric ulceration process, were measured. Most studies have shown that fruit extracts have antiulcer activity, with the most abundant metabolites being flavonoids, followed by terpenes and alkaloids. Possible antiulcer activities such as antioxidant, cytoprotective, gastric acid antisecretory, anti-inflammatory, or angiogenesis stimulant were declared, manifested mainly as a reduction of lipid peroxidation products, an increase in antioxidant enzymes and prostaglandins, and by the formation of a protective film through protein precipitation in the ulcer area. This systematic review demonstrates the importance of fruit extracts as gastric protectors.
Topics: Rats; Animals; Stomach Ulcer; Antioxidants; Fruit; Gastric Mucosa; Plant Extracts; Rats, Wistar; Anti-Ulcer Agents; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Aspirin
PubMed: 37902784
DOI: 10.1089/jmf.2023.0005 -
Journal of Assisted Reproduction and... Feb 2024Although significant improvements in assisted reproductive technology (ART) outcomes have been accomplished, a critical question remains: which embryo is most likely to... (Review)
Review
PURPOSE
Although significant improvements in assisted reproductive technology (ART) outcomes have been accomplished, a critical question remains: which embryo is most likely to result in a pregnancy? Embryo selection is currently based on morphological and genetic criteria; however, these criteria do not fully predict good-quality embryos and additional objective criteria are needed. The cumulus cells are critical for oocyte and embryo development. This systematic review assessed biomarkers in cumulus-oocyte complexes and their association with successful IVF outcomes.
METHODS
A comprehensive search was conducted using PubMed, Embase, Scopus, and Web of Science from inception until November 2022. Only English-language publications were included. Inclusion criteria consisted of papers that evaluated genetic biomarkers associated with the cumulus cells (CCs) in humans and the following three outcomes of interest: oocyte quality, embryo quality, and clinical outcomes, including fertilization, implantation, pregnancy, and live birth rates.
RESULTS
The search revealed 446 studies of which 42 met eligibility criteria. Nineteen studies correlated genetic and biochemical biomarkers in CCs with oocyte quality. A positive correlation was reported between oocyte quality and increased mRNA expression in CCs of genes encoding for calcium homeostasis (CAMK1D), glucose metabolism (PFKP), extracellular matrix (HAS2, VCAN), TGF-β family (GDF9, BMP15), and prostaglandin synthesis (PTGS2). Nineteen studies correlated genetic and biochemical biomarkers in CCs with embryo quality. A positive correlation was reported between embryo quality and increased mRNA expression in CCs of genes encoding for extracellular matrix (HAS2), prostaglandin synthesis (PTGS2), steroidogenesis (GREM1), and decreased expression of gene encoding for hormone receptor (AMHR2). Twenty-two studies assessed genetic and biochemical biomarkers in CCs with clinical outcomes. Increased expression of genes encoding for extracellular matrix (VCAN), and TGF-β family (GDF9, BMP15) were positively correlated with pregnancy rate.
CONCLUSION
Genetic biomarkers from cumulus cells were associated with oocyte quality (CAMK1D, PFKP, HAS2, VCAN, GDF-9, BMP-15, PTGS2), embryo quality (GREM1, PTGS2, HAS2), and pregnancy rate (GDF9, BMP15, VCAN). These results might help guide future studies directed at tests of cumulus cells to devise objective criteria to predict IVF outcomes.
Topics: Pregnancy; Female; Humans; Cumulus Cells; Cyclooxygenase 2; Oocytes; Fertilization in Vitro; Reproductive Techniques, Assisted; Genetic Markers; RNA, Messenger; Transforming Growth Factor beta; Prostaglandins
PubMed: 37947940
DOI: 10.1007/s10815-023-02984-9 -
The Cochrane Database of Systematic... Aug 2016Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric... (Review)
Review
BACKGROUND
Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review.
OBJECTIVES
To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 12 May 2016.
SELECTION CRITERIA
All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment.
DATA COLLECTION AND ANALYSIS
Both authors independently selected trials, assessed trial quality and extracted data.
MAIN RESULTS
The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival.
AUTHORS' CONCLUSIONS
Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
Topics: Abdominal Pain; Adult; Child; Cystic Fibrosis; Dietary Fats; Gastric Acid; Gastrointestinal Agents; Histamine H2 Antagonists; Humans; Intestinal Absorption; Pancreas; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 27546383
DOI: 10.1002/14651858.CD003424.pub4 -
Journal of Nutritional Science 2021Dietary -3 polyunsaturated fatty acids (PUFAs) present beneficial effects on counteracting inflammation status, displaying a critical anti-inflammatory role and... (Meta-Analysis)
Meta-Analysis Review
Effect of -3 long-chain polyunsaturated fatty acid intake on the eicosanoid profile in individuals with obesity and overweight: a systematic review and meta-analysis of clinical trials.
Dietary -3 polyunsaturated fatty acids (PUFAs) present beneficial effects on counteracting inflammation status, displaying a critical anti-inflammatory role and maintaining physiological homeostasis in obesity. The primary objective of this systematic review was to evaluate the effect of -3 PUFAs intake on the eicosanoid profile of people with obesity and overweight. The search strategy on Embase, Scopus, PubMed, Web of Science, Cochrane Library, Google Scholar and ProQuest was undertaken until November 2019 and updated January 2021. The effect size of -3 PUFAs on prostaglandins was estimated by Glass's, type 1 in a random-effect model for the meta-analysis. Seven clinical trials met the eligible criteria and a total of 610 subjects were included in this systematic review, and four of seven studies were included in meta-analysis. The intake of -3 PUFAs promoted an overall reduction in serum pro-inflammatory eicosanoids. Additionally, -3 PUFAs intake significantly decreased the arachidonic acid COX-derived PG eicosanoid group levels (Glass's Δ -0⋅35; CI -0⋅62, -0⋅07, 31⋅48). Subgroup analyses showed a higher effect on periods up to 8 weeks (Glass's Δ -0⋅51; CI -0⋅76, -0⋅27) and doses higher than 0⋅5 g of -3 PUFAs (Glass's Δ -0⋅46; CI -0⋅72, -0⋅27). Dietary -3 PUFAs intake contributes to reduce pro-inflammatory eicosanoids of people with obesity and overweight. Subgroup's analysis showed that -3 PUFAs can reduce the overall arachidonic acid COX-derived PG when adequate dose and period are matched.
Topics: Arachidonic Acid; Clinical Trials as Topic; Eicosanoids; Fatty Acids, Omega-3; Humans; Obesity; Overweight
PubMed: 34367628
DOI: 10.1017/jns.2021.46 -
Prostaglandins & Other Lipid Mediators Dec 2022Conjugated Linoleic Acid (CLA) are thought to pose beneficial effects on inflammatory responses and oxidative stress (OS). Thus, the present systematic review and... (Meta-Analysis)
Meta-Analysis Review
Conjugated Linoleic Acid (CLA) are thought to pose beneficial effects on inflammatory responses and oxidative stress (OS). Thus, the present systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the net effects of CLA supplementation on various OS parameters and antioxidant enzymes. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched for publications on CLA supplementation effects on OS parameters up to March 2021. The data extracted from eligible studies were expressed as standardized mean difference with 95% confidence intervals and then combined into meta-analysis using the random-effects model. Overall, 11 RCTs (enrolling 586 participants) met the inclusion criteria and were included in meta-analysis; however, since those trials evaluated different OS parameters, meta-analysis was carried out considering different sets for each parameter separately. According to our results, CLA supplementation significantly increases 8-iso-PGF urinary concentration (SMD: 2; 95% CI: 0.74, 3.27; I = 87.7%). On contrary, the intervention does not seem to change 15-keto-dihydro-PGF urinary concentration, nor the serum levels of CAT, SOD, GPx and MDA. Taken all together, CLA supplementation does not appear to have substantial effects on OS markers in general; albeit due to relatively small sample size and high level of heterogeneity between studies, the obtained findings should be interpreted with caution. Further large well-designed RCTs, investigating the impact of CLA and including various groups of patients, are still needed.
Topics: Linoleic Acids, Conjugated; Antioxidants; Dietary Supplements; Randomized Controlled Trials as Topic; Oxidative Stress
PubMed: 35914666
DOI: 10.1016/j.prostaglandins.2022.106666 -
CNS & Neurological Disorders Drug... 2022Multiple sclerosis (MS) is an inflammatory neurodegenerative disease characterized by destruction of oligodendrocytes, immune cell infiltration and demyelination....
BACKGROUND AND OBJECTIVE
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease characterized by destruction of oligodendrocytes, immune cell infiltration and demyelination. Inflammation plays a significant role in MS, and the inflammatory mediators such as eicosanoids, leukotrienes, and superoxide radicals are involved in pro-inflammatory responses in MS. In this systematic review, we tried to define and discuss all the findings of in vivo animal studies and human clinical trials on the potential association between arachidonic acid (AA) pathway and multiple sclerosis.
METHODS
A systematic literature search across Pubmed, Scopus, Embase and Cochrane database was conducted. This systematic review was performed according to PRISMA guidelines.
RESULTS
A total of 146 studies were included, of which 34 were conducted on animals, 58 on humans, and 60 studies reported the role of different compounds that target AA mediators or their corresponding enzymes/receptors, and can have a therapeutic effect in MS. These results suggest that eicosanoids have significant roles in Experimental Autoimmune Encephalomyelitis (EAE) and MS. The data from animal and human studies elucidated that PGI, PGFI, PGDI, isoprostanes, PGEI, PLAI, and LTs are increased in MS. PLAI inhibition modulates the progression of the disease. PGE1 analogues can be a useful option in the treatment of MS.
CONCLUSION
All studies reported the beneficial effects of COX and LOX inhibitors in MS. The hybrid compounds, such as COX-2 inhibitors/TP antagonists and 5-LOX inhibitors, can be an innovative approach for multiple sclerosis treatment. Future work in MS should shed light on synthesizing new compounds targeting the arachidonic acid pathway.
Topics: Animals; Arachidonic Acid; Eicosanoids; Encephalomyelitis, Autoimmune, Experimental; Humans; Inflammation; Multiple Sclerosis
PubMed: 32842948
DOI: 10.2174/1871527319666200825164123 -
Prostaglandins & Other Lipid Mediators Feb 2007According to current literature, infective processes greatly modify both vascular hemodynamics and anti-oxidant properties of affected tissues, causing a change in... (Review)
Review
According to current literature, infective processes greatly modify both vascular hemodynamics and anti-oxidant properties of affected tissues, causing a change in homeostasis that regulates the correct functioning of all cells responsible for the physiological and metabolic balance of various organs. As a consequence, the response to the infection that has caused the change is also likely to be weaker and, in the case of septic shock, ineffective. In this review, we will take into consideration these mechanisms and then focus on a group of vasodilator drugs (prostacyclin and its analogs) which, though have been used for over 20 years mainly to treat obstructive vascular diseases, have such hemodynamic and anti-inflammatory properties which prevent homeostatic changes. It is obvious that prostacyclin does not definitively have anti-infective characteristics; however, in association with anti-infective drugs (antibiotics, etc.), the effectiveness of the latter appears improved, at least in some circumstances. Similarly, the fact that prostacyclin and its analogs have a cytoprotective effect on the liver and reduce the ischemia-reperfusion damage following liver transplant is not a novelty and evidence that they improve hepatic hemodynamics suggests their use in those pathologies characterized by possible reduced perfusion or ascertained ischemia of the liver.
Topics: Animals; Endothelium, Vascular; Epoprostenol; Humans; Reperfusion Injury; Sepsis; Splanchnic Circulation
PubMed: 17259068
DOI: 10.1016/j.prostaglandins.2006.12.004 -
Chest Jun 2015This study aimed to determine whether inhaled prostaglandins are associated with improvement in pulmonary physiology or mortality in patients with ARDS and assess... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to determine whether inhaled prostaglandins are associated with improvement in pulmonary physiology or mortality in patients with ARDS and assess adverse effects.
METHODS
The following data sources were used: PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, reference lists, conference proceedings, and ClinicalTrials.gov. Studies selected included randomized controlled trials and nonrandomized studies. For data extraction, two reviewers independently screened titles and abstracts for eligibility. With regard to data synthesis, 25 studies (two RCTs) published over 21 years (1993-2014) were included. The PROSPERO registration number was CRD42014013180.
RESULTS
One randomized controlled trial showed no difference in the change in mean Pao2 to Fio2 ratio when comparing inhaled alprostadil to placebo: 141.2 (95% CI, 120.8-161.5) to 161.5 (95% CI, 134.6-188.3) vs 163.4 (95% CI, 140.8-186.0) to 186.8 (95% CI, 162.9-210.7), P = .21. Meta-analysis of the remaining studies demonstrated that inhaled prostaglandins were associated with improvement in Pao2 to Fio2 ratio (16 studies; 39.0% higher; 95% CI, 26.7%-51.3%), and Pao2 (eight studies; 21.4% higher; 95% CI, 12.2%-30.6%), and a decrease in pulmonary artery pressure (-4.8 mm Hg; 95% CI, -6.8 mm Hg to -2.8 mm Hg). Risk of bias and heterogeneity were high. Meta-regression found no association with publication year (P = .862), baseline oxygenation (P = .106), and ARDS etiology (P = .816) with the treatment effect. Hypotension occurred in 17.4% of patients in observational studies.
CONCLUSIONS
In ARDS, inhaled prostaglandins improve oxygenation and decrease pulmonary artery pressures and may be associated with harm. Data are limited both in terms of methodologic quality and demonstration of clinical benefit. The use of inhaled prostaglandins in ARDS needs further study.
Topics: Administration, Inhalation; Humans; Lung; Oxygen; Prostaglandins; Pulmonary Artery; Respiratory Distress Syndrome; Treatment Outcome
PubMed: 25742022
DOI: 10.1378/chest.14-3161 -
International Urology and Nephrology Nov 2016Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse... (Review)
Review
PURPOSE
Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium-associated renal disease.
METHODS
We conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium's effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers.
RESULTS
From a total of 3510 records, 71 pre-clinical studies and two relevant clinical studies were identified. Molecular alterations were reported in calcium signaling, inositol monophosphate, extracellular-regulated, prostaglandin, sodium/solute transport, G-protein-coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation-related pathways in lithium-associated renal disease. The majority of studies found that these mechanisms were implicated in NDI, while few studies had examined CKD.
DISCUSSION
Future studies will have to focus on (1) validating the present findings in human subjects and (2) examining CKD, which is the most clinically relevant lithium-associated renal effect. This will improve our understanding of lithium's biological effects, as well as inform a personalized medicine approach, which could lead to safer lithium prescribing and less renal adverse events.
Topics: Animals; Aquaporins; Calcium; Diabetes Insipidus, Nephrogenic; Humans; Lithium; Prostaglandins; Receptors, G-Protein-Coupled; Renal Insufficiency, Chronic; Signal Transduction; Sodium; Symporters; Vasopressins
PubMed: 27357223
DOI: 10.1007/s11255-016-1352-6