1,721,268 research outputs found
In vivo and in vitro evaluation of post-translational LDL apoprotein B modification induced by homocysteine
No full textCovalent alterations of LDL by acetylation, oxidation or glycation, increase lipoprotein uptake and cholesterol deposition within cultured cells. Besides, oxidized or glycated LDL induce lipid peroxidation in cultured cells. N-homocysteinylation of LDL has been described as proatherogeinc event since Hcy-N-LDL show a cytotoxic effect that is likely related to an increase in lipid peroxidation and oxidative damage of endothelial cells and multimeric aggregation. Despite the plentiful data about the other covalent modification of LDL the S-homocysteynilation of lipoprotein has been at now slightly studied. By this work we propose the first method able to measure simultaneously all thiols linked to LDL apoprotein. This allows us to investigate on the levels of thiols bound to LDL in a group of healthy subjects to define the normal range of this thiol in vivo. Besides we describe the ability of Hcy to bind LDL in vitro also displacing the other thiols linked to apoprotein. Moreover for the first time we show the citotoxic effect of LDL on endothelial cells demonstrated by the decrease proliferation and viability of cells incubated with homocysteinylated LDL. Even though the mechanism by which Hcy-S-LDL exert their toxic effect still remains to be elucidated, our data suggest that intracellular ROS production stimulated after incubation with Hcy-S-LDL may have some relevance
The diagnostic role of the systemic inflammation index in patients with immunological diseases: a systematic review and meta-analysis
No full textThe identification of novel, easily measurable biomarkers of inflammation might enhance the diagnosis and management of immunological diseases (IDs). We conducted a systematic review and meta-analysis to investigate an emerging biomarker derived from the full blood count, the systemic inflammation index (SII), in patients with IDs and healthy controls. We searched Scopus, PubMed, and Web of Science from inception to 12 December 2023 for relevant articles and evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 16 eligible studies, patients with IDs had a significantly higher SII when compared to controls (standard mean difference, SMD = 1.08, 95% CI 0.75 to 1.41, p < 0.001; I-2 = 96.2%, p < 0.001; moderate certainty of evidence). The pooled area under the curve (AUC) for diagnostic accuracy was 0.85 (95% CI 0.82-0.88). In subgroup analysis, the effect size was significant across different types of ID, barring systemic lupus erythematosus (p = 0.20). In further analyses, the SII was significantly higher in ID patients with active disease vs. those in remission (SMD = 0.81, 95% CI 0.34-1.27, p < 0.001; I-2 = 93.6%, p < 0.001; moderate certainty of evidence). The pooled AUC was 0.74 (95% CI 0.70-0.78). Our study suggests that the SII can effectively discriminate between subjects with and without IDs and between ID patients with and without active disease. Prospective studies are warranted to determine whether the SII can enhance the diagnosis of IDs in routine practice. (PROSPERO registration number: CRD42023493142)
A systematic review and meta-analysis of neopterin in rheumatic diseases
No full textIntroduction Novel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs). We assessed the available evidence regarding the pathophysiological role of neopterin, the oxidation product of 7,8-dihydroneopterin, a pteridine generated in macrophages activated by interferon-gamma, by conducting a systematic review and meta-analysis of studies reporting its concentrations in biological fluids in RD patients and healthy controls.Methods We searched electronic databases for relevant articles published between inception and 31 August 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system, respectively.Results In 37 studies, when compared to healthy controls, RD patients had significantly higher concentrations of neopterin both in plasma or serum (standard mean difference, SMD=1.31, 95% CI 1.01 to 1.61; p<0.001; moderate certainty of evidence) and in the urine (SMD=1.65, 95% CI 0.86 to 2.43, p<0.001; I2 = 94.2%, p<0.001; low certainty of evidence). The results were stable in sensitivity analysis. There were non-significant associations in meta-regression and subgroup analysis between the effect size and age, male to female ratio, year of publication, sample size, RD duration, C-reactive protein, erythrocyte sedimentation rate, specific type of RD, presence of connective tissue disease, analytical method used, or biological matrix investigated (plasma vs. serum). By contrast, the effect size was significantly associated with the geographical area in studies assessing serum or plasma and with the type of RD in studies assessing urine.Discussion Pending additional studies that also focus on early forms of disease, our systematic review and meta-analysis supports the proposition that neopterin, a biomarker of inflammation and oxidative stress, can be useful for the identification of RDs. (PROSPERO registration number: CRD42023450209).Systematic review registration PROSPERO, identifier CRD4202345020
Effect of statin treatment on homocysteine concentrations: an updated systematic review and meta-analysis with meta-regression
No full textBackground and aims: Statins might exert atheroprotective effects through lowering the pro-atherogenic amino acid homocysteine. We addressed this issue by conducting an updated systematic review and meta-analysis of the effect of statins on circulating homocysteine. Methods: A systematic literature search was conducted in PubMed, Web of Science, and Scopus, from inception to July 2021. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies. Certainty of evidence was assessed using GRADE. Results: In 61 treatment arms in 2,218 patients (mean age 55 years, 52% males), statins significantly reduced homocysteine concentrations (weighted mean difference, WMD=-2.46 μmol/L, 95% CI -3.17 to -1.75 μmol/L, p<0.001; high certainty of evidence). Similar results were observed in a subgroup of 10 randomized placebo-controlled studies (WMD=-2.45 μmol/L, 95% CI -4.43 to -0.47 μmol/L, p=0.015). The extreme heterogeneity observed was virtually removed in a subgroup of 10 studies using fluorescence polarization immunoassay for homocysteine measurement. There was no publication bias. In sensitivity analysis, the pooled WMD values were not modified when individual studies were sequentially removed. In meta-regression, the WMD was significantly associated with proportion of males and publication year. Conclusions: Statins significantly lower homocysteine concentrations (PROSPERO registration number: CRD42021273963)
Transsulfuration and folate pathways in rheumatoid arthritis: A systematic review and meta-analysis
No full textBackground: Metabolomic assessment of the transsulfuration and folic acid biochemical pathways could lead to the identification of promising biomarkers of nitric oxide dysregulation and oxidative stress in rheumatoid arthritis (RA). Methods: We conducted a systematic review and meta-analysis of transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6 , and vitamin B12 ) metabolites in RA patients in remission and healthy controls. Electronic databases were searched from inception to 15 July 2023 for relevant articles. We assessed the risk of bias using the JBI checklist and the certainty of evidence using GRADE. Results: In 28 eligible studies, compared to controls, RA patients had significantly higher concentrations of homocysteine (standardized mean difference, SMD = 0.74, 95% CI 0.54-0.93, p < 0.001; low certainty of evidence) and methionine (SMD = 1.00, 95% CI 0.57-1.44, p < 0.001; low certainty) and lower concentrations of vitamin B6 (SMD = -6.62, 95% CI -9.65 to -3.60, p < 0.001; low certainty). By contrast, there were non-significant between-group differences in vitamin B12 and folic acid. In meta-regression and subgroup analysis, there were no associations between the effect size and several study and patient characteristics except for homocysteine (year of publication, C-reactive protein, triglycerides, and analytical method) and folic acid (biological matrix). Conclusions: The results of our study suggest that homocysteine, methionine, and vitamin B6 are promising biomarkers to assess nitric oxide dysregulation and oxidative stress in RA. (PROSPERO registration number: CRD42023461081)
The potential role of serum amyloid A as biomarker of rheumatic diseases: a systematic review and meta-analysis
No full text: The identification of novel, robust biomarkers for the diagnosis of rheumatic diseases (RDs) and the presence of active disease might facilitate early treatment and the achievement of favourable long-term outcomes. We conducted a systematic review and meta-analysis of studies investigating the acute phase reactant, serum amyloid A (SAA), in RD patients and healthy controls to appraise its potential as diagnostic biomarker. We searched PubMed, Scopus, and Web of Science from inception to 10 April 2024 for relevant studies. We evaluated the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024537418). In 32 studies selected for analysis, SAA concentrations were significantly higher in RD patients compared to controls (SMD = 1.61, 95% CI 1.24-1.98, p < 0.001) and in RD patients with active disease compared to those in remission (SMD = 2.17, 95% CI 1.21-3.13, p < 0.001). Summary receiving characteristics curve analysis showed a good diagnostic accuracy of SAA for the presence of RDs (area under the curve = 0.81, 95% CI 0.78-0.84). The effect size of the differences in SAA concentrations between RD patients and controls was significantly associated with sex, body mass index, type of RD, and study country. Pending the conduct of prospective studies in different types of RDs, the results of this systematic review and meta-analysis suggest that SAA is a promising biomarker for the diagnosis of RDs and active disease
A systematic review and meta-analysis of the association between the neutrophil, lymphocyte, and platelet count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio and COVID-19 progression and mortality
No full textBackground and aims Severe manifestations of coronavirus disease 2019 (COVID-19) are associated with alterations in blood cells that regulate immunity, inflammation, and hemostasis. We conducted an updated systematic review and meta-analysis of the association between the neutrophil, lymphocyte, and platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), and COVID-19 progression and mortality. Methods A systematic literature search was conducted in PubMed, Web of Science, and Scopus for studies published between January 2020 and June 2022. Results In 71 studies reporting the investigated parameters within 48 hours of admission, higher NLR (HR 1.21, 95% CI 1.16 to 1.27, p < 0.0001), relative neutrophilia (HR 1.62, 95% CI 1.46 to 1.80, p < 0.0001), relative lymphopenia (HR 1.62, 95% CI 1.27 to 2.08, p < 0.001), and relative thrombocytopenia (HR 1.74, 95% CI 1.36 to 2.22, p < 0.001), but not PLR (p = 0.11), were significantly associated with disease progression and mortality. Between-study heterogeneity was large-to-extreme. The magnitude and direction of the effect size were not modified in sensitivity analysis. Conclusions NLR and neutrophil, lymphocyte, and platelet count significantly discriminate COVID-19 patients with different progression and survival outcomes. (PROSPERO registration number: CRD42021267875)
Systemic inflammation index, disease severity, and mortality in patients with COVID-19: a systematic review and meta-analysis
No full textIntroduction An excessive systemic pro-inflammatory state increases the risk of severe disease and mortality in patients with coronavirus disease 2019 (COVID-19). However, there is uncertainty regarding whether specific biomarkers of inflammation can enhance risk stratification in this group. We conducted a systematic review and meta-analysis to investigate an emerging biomarker of systemic inflammation derived from routine hematological parameters, the systemic inflammation index (SII), in COVID-19 patients with different disease severity and survival status.Methods A systematic literature search was conducted in PubMed, Web of Science, and Scopus, between the 1(st) of December 2019 and the 15(th) of March 2023. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation, respectively (PROSPERO registration number: CRD42023420517).Results In 39 studies, patients with a severe disease or non-survivor status had significantly higher SII values on admission compared to patients with a non-severe disease or survivor status (standard mean difference (SMD)=0.91, 95% CI 0.75 to 1.06, p<0.001; moderate certainty of evidence). The SII was also significantly associated with the risk of severe disease or death in 10 studies reporting odds ratios (1.007, 95% CI 1.001 to 1.014, p=0.032; very low certainty of evidence) and in six studies reporting hazard ratios (1.99, 95% CI 1.01 to 3.92, p=0.047; very low certainty of evidence). Pooled sensitivity, specificity, and area under the curve for severe disease or mortality were 0.71 (95% CI 0.67 to 0.75), 0.71 (95% CI 0.64 to 0.77), and 0.77 (95% CI 0.73 to 0.80), respectively. In meta-regression, significant correlations were observed between the SMD and albumin, lactate dehydrogenase, creatinine, and D-dimer.Discussion Our systematic review and meta-analysis has shown that the SII on admission is significantly associated with severe disease and mortality in patients with COVID-19. Therefore, this inflammatory biomarker derived from routine haematological parameters can be helpful for early risk stratification in this group
A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases
No full textThere is an increasing interest in the pathophysiological role of the kynurenine pathway of tryptophan metabolism in the regulation of immune function and inflammation. We sought to address the link between this pathway and the presence rheumatic diseases (RD) by conducting a systematic review and meta-analysis of studies reporting the plasma or serum concentrations of tryptophan, kynurenine, and other relevant metabolites in RD patients and healthy controls. We searched electronic databases for relevant articles published between inception and the 30th of June 2023. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system. In 24 studies selected for analysis, compared to controls, RD patients had significantly lower tryptophan (standard mean difference, SMD= -0.71, 95% CI -1.03 to -0.39, p<0.001; I-2 = 93.6%, p<0.001; low certainty of evidence), and higher kynurenine (SMD=0.69, 95% CI 0.35 to 1.02, p<0.001; I2 = 93.2%, p<0.001; low certainty), kynurenine to tryptophan ratios (SMD=0.88, 95% CI 0.55 to 1.21, p<0.001; I-2 = 92.9%, p<0.001; moderate certainty), 3-hydroxykynurenine (SMD=0.74, 95% CI 0.30 to 1.18, p=0.001; I-2 = 87.7%, p<0.001; extremely low certainty), and quinolinic acid concentrations (SMD=0.71, 95% CI 0.31 to 1.11, p<0.001; I-2 = 88.1%, p<0.001; extremely low certainty). By contrast, there were non-significant between-group differences in kynurenic acid, 3-hydroxyanthranilic acid, kynurenic acid to kynurenine ratio, or quinolinic acid to kynurenine acid ratio. In meta-regression, the SMD of tryptophan, kynurenine, and kynurenine to tryptophan ratio were not associated with age, publication year, sample size, RD duration, C-reactive protein, or use of anti-rheumatic drugs and corticosteroids. In subgroup analysis, the SMD of tryptophan, kynurenine, and kynurenine to tryptophan ratio was significant across different types of RD, barring rheumatoid arthritis. Therefore, we have observed significant alterations in tryptophan, kynurenine, 3-hydroxykynurenine, and quinolinic acid concentrations in RD patients. Further research is warranted to determine whether these biomarkers can be useful for diagnosis and management in this patient group. (PROSPERO registration number: CRD CRD42023443718)
A systematic review and meta-analysis of circulating adhesion molecules in rheumatoid arthritis
No full textBackground: The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We investigated this issue by conducting a systematic review and meta-analysis of cell adhesion molecules in RA patients. Methods: We searched electronic databases from inception to 31 July 2023 for case-control studies assessing the circulating concentrations of immunoglobulin-like adhesion molecules (vascular cell, VCAM-1, intercellular, ICAM-1, and platelet endothelial cell, PECAM-1, adhesion molecule-1) and selectins (E, L, and P selectin) in RA patients and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively. Results: In 39 studies, compared to controls, RA patients had significantly higher concentrations of ICAM-1 (standard mean difference, SMD = 0.81, 95% CI 0.62-1.00, p < 0.001; I2 = 83.0%, p < 0.001), VCAM-1 (SMD = 1.17, 95% CI 0.73-1.61, p < 0.001; I2 = 95.8%, p < 0.001), PECAM-1 (SMD = 0.82, 95% CI 0.57-1.08, p < 0.001; I2 = 0.0%, p = 0.90), E-selectin (SMD = 0.64, 95% CI 0.42-0.86, p < 0.001; I2 = 75.0%, p < 0.001), and P-selectin (SMD = 1.06, 95% CI 0.50-1.60, p < 0.001; I2 = 84.8%, p < 0.001), but not L-selectin. In meta-regression and subgroup analysis, significant associations were observed between the effect size and use of glucocorticoids (ICAM-1), erythrocyte sedimentation rate (VCAM-1), study continent (VCAM-1, E-selectin, and P-selectin), and matrix assessed (P-selectin). Conclusions: The results of our study support a significant role of cell adhesion molecules in mediating the interplay between RA and atherosclerosis. Further studies are warranted to determine whether the routine use of these biomarkers can facilitate the detection and management of early atherosclerosis in this patient group. PROSPERO Registration Number: CRD42023466662
- …
