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Frontiers in Immunology 2021B cells can contribute to immune-mediated disorders. Targeting CD20 has proved to be efficacious in several B cell-mediated immunopathologies, as illustrated by the use...
BACKGROUND
B cells can contribute to immune-mediated disorders. Targeting CD20 has proved to be efficacious in several B cell-mediated immunopathologies, as illustrated by the use of rituximab, the first anti-CD20 monoclonal antibody (mAb). Following rituximab, second- and third-generation anti-CD20 mAbs have been developed and tried in immune-mediated diseases, including obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab. However, their safety and efficacy has not been systematically reviewed.
OBJECTIVE
To evaluate safety and efficacy of obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics.
METHODS
The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 22 July 2021 concentrating on immune-mediated disorders.
RESULTS
The literature search identified 2220 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 27 articles were finally included in a narrative synthesis.
CONCLUSIONS
Obinutuzumab has shown promising results in a case series of patients with phospholipase A receptor-associated membranous nephropathy and mixed results in systemic lupus erythematosus. Ocrelizumab has been approved for the use in patients with relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis. Ocrelizumab was also tested in patients with rheumatoid arthritis, demonstrating promising results, and in systemic lupus erythematosus, revealing mixed results; however, in these conditions, its use was associated with increased risk of serious infections. Ofatumumab received approval for treating patients with relapsing-remitting multiple sclerosis. Moreover, ofatumumab showed promising results in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, rheumatoid arthritis, and systemic lupus erythematosus, as well as mixed results in phospholipase A receptor-associated membranous nephropathy. Ublituximab was assessed in relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder, with promising results, however, the included number of patients was too small to conclude. Veltuzumab was tested in patients with immune thrombocytopenia resulting in improved platelet counts.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD4201913421.
Topics: Antigens, CD20; Arthritis, Rheumatoid; Biological Products; Glomerulonephritis, Membranous; Humans; Immune System Diseases; Lupus Erythematosus, Systemic; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Phospholipases; Rituximab
PubMed: 35185862
DOI: 10.3389/fimmu.2021.788830 -
International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
Pathogens (Basel, Switzerland) Dec 2021Protozoal infection is a lingering public health issue of great concern, despite efforts to produce drugs and vaccines against it. Recent breakthrough research has... (Review)
Review
BACKGROUND
Protozoal infection is a lingering public health issue of great concern, despite efforts to produce drugs and vaccines against it. Recent breakthrough research has discovered alternative antiprotozoal agents encompassing the use of snake venoms and their components to cure these infections. This study collated the existing literature to examine the antiprotozoal effect of snake venoms and their fractions.
METHODS
We conducted a systematic review following the PRISMA guidelines. The PubMed and Embase databases were searched from their inception until 13 October 2021. Articles were screened at the title, abstract and full-text phases. Some additional studies were obtained through the manual search process.
RESULTS
We identified 331 studies via the electronic database and manual searches, of which 55 reporting the antiprotozoal effect of snake venoms and their components were included in the review. Around 38% of studies examined the effect of whole crude venoms, and a similar percentage evaluated the effect of a proportion of enzymatic phospholipase A2 (PLA2). In particular, this review reports around 36 PLA2 activities and 29 snake crude venom activities. We also report the notable phenomenon of synergism with PLA2 isoforms of . Importantly, limited attention has been given so far to the antiprotozoal efficacies of metalloproteinase, serine protease and three-finger toxins, although these venom components have been identified as significant components of the dominant venom families.
CONCLUSION
This study highlights the impact of snake venoms and their fractions on controlling protozoal infections and suggests the need to examine further the effectiveness of other venom components, such as metalloproteinase, serine protease and three-finger toxins. Future research questions in this field must be redirected toward synergism in snake venom components, based on pharmacological usage and in the context of toxicology. Ascertaining the effects of snake venoms and their components on other protozoal species that have not yet been studied is imperative.
PubMed: 34959587
DOI: 10.3390/pathogens10121632 -
Movement Disorders : Official Journal... Jan 2022Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration.
BACKGROUND
Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration.
OBJECTIVES
The aim of this study was to deeply characterize phenogenotypically PLA2G6-related parkinsonism in the largest cohort ever reported.
METHODS
We report 14 new cases of PLA2G6-related parkinsonism and perform a systematic literature review.
RESULTS
PLA2G6-related parkinsonism shows a fairly distinct phenotype based on 86 cases from 68 pedigrees. Young onset (median age, 23.0 years) with parkinsonism/dystonia, gait/balance, and/or psychiatric/cognitive symptoms were common presenting features. Dystonia occurred in 69.4%, pyramidal signs in 77.2%, myoclonus in 65.2%, and cerebellar signs in 44.6% of cases. Early bladder overactivity was present in 71.9% of cases. Cognitive impairment affected 76.1% of cases and psychiatric features 87.1%, the latter being an isolated presenting feature in 20.1%. Parkinsonism was levodopa responsive but complicated by early, often severe dyskinesias. Five patients benefited from deep brain stimulation. Brain magnetic resonance imaging findings included cerebral (49.3%) and/or cerebellar (43.2%) atrophy, but mineralization was evident in only 28.1%. Presynaptic dopaminergic terminal imaging was abnormal in all where performed. Fifty-four PLA2G6 mutations have hitherto been associated with parkinsonism, including four new variants reported in this article. These are mainly nontruncating, which may explain the phenotypic heterogeneity of childhood- and late-onset PLA2G6-associated neurodegeneration. In five deceased patients, median disease duration was 13.0 years. Brain pathology in three cases showed mixed Lewy and tau pathology.
CONCLUSIONS
Biallelic PLA2G6 mutations cause early-onset parkinsonism associated with dystonia, pyramidal and cerebellar signs, myoclonus, and cognitive impairment. Early psychiatric manifestations and bladder overactivity are common. Cerebro/cerebellar atrophy are frequent magnetic resonance imaging features, whereas brain iron deposition is not. Early, severe dyskinesias are a tell-tale sign. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Age of Onset; Atrophy; Dystonia; Genotype; Group VI Phospholipases A2; Humans; Mutation; Parkinsonian Disorders; Pedigree; Phenotype
PubMed: 34622992
DOI: 10.1002/mds.28807 -
Cancer Epidemiology Oct 2023Oral squamous cell carcinoma (OSCC) is considered a multifactorial disease and has been associated with microbial infections, although the association with Candida spp.... (Review)
Review
Oral squamous cell carcinoma (OSCC) is considered a multifactorial disease and has been associated with microbial infections, although the association with Candida spp. is still controversial. This systematic review focused on clinical trials which evaluated the relation between oral Candida spp colonization and OSCC. PubMed; Scopus; Embase; Web of Science and Scientific Direct were assessed. Independent reviewers conducted the diagram steps. For data extraction the PRISMA protocol was followed. The quality analysis of case-control studies was performed based on the Newcastle-Ottawa scale. Meta-analysis was performed to evaluate the frequency of Candida spp and the levels of microbial acetaldehyde production (MAP) being odds ratio (OR) the effect-measure applied. Eight and six studies were included in the qualitative analysis and meta-analysis, respectively. It was noted that there was a significantly higher frequency of Candida species (p = 0.0003/OR = 9.50) in patients diagnosed with OSCC than healthy patients, especially Candida krusei (p = 0.0167/OR=4.62). Candida spp., from oral cancer patients demonstrated significantly greater biofilm, biofilm metabolic activity, phospholipase, proteinase activity and a higher production of MAP (p = 0.0111/OR = 2.67). Candida species may have a potential role in OSCC development. Further studies should be conducted to elucidate the mechanism of action of Candida spp and others risk factors in the development of OSCC.
PubMed: 37716154
DOI: 10.1016/j.canep.2023.102451 -
Current Pharmaceutical Design 2020The timely identification of traditional and non-traditional precursors and risk factors for chronic kidney disease (CKD) (a common systemic disease defined as a...
BACKGROUND
The timely identification of traditional and non-traditional precursors and risk factors for chronic kidney disease (CKD) (a common systemic disease defined as a decreased kidney function documented by reduced glomerular filtration rate, or markers of kidney damage, or both) is relevant in clinical practice, as CKD increases the risk of end-stage renal disease and other serious comorbidities. A possible relationship between non-alcoholic fatty liver disease (NAFLD) (which is to date the most common chronic disease worldwide) and CKD has recently gained significant attention of researchers.
METHODS
A systematic literature search using appropriate keywords was made in order to identify relevant articles that have investigated the association between NAFLD and CKD.
RESULTS
Several observational studies and meta-analyses have reported the existence of an independent association between NAFLD and risk of CKD in patients with and without diabetes. However, whilst the association between NAFLD and risk of prevalent CKD is strong across various patient populations, whether NAFLD is independently associated with the development and progression of CKD is still debatable. Moreover, emerging evidence now suggests a potential association between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 genotype (the most important genetic variant associated to NAFLD) and decreasing kidney function, independent of NAFLD.
CONCLUSION
Convincing evidence now indicates that CKD is increased among patients with NAFLD. For this reason, patients with NAFLD should be regularly monitored for renal function and, on the other hand , NAFLD should be considered in all patients with CKD, especially if they are obese or have type 2 diabetes.
Topics: Comorbidity; Humans; Kidney Failure, Chronic; Lipase; Membrane Proteins; Non-alcoholic Fatty Liver Disease; Risk Factors
PubMed: 31738141
DOI: 10.2174/1381612825666191026113119 -
Medicine Apr 2020Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND OBJECTIVES
Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain uncertain. This meta-analysis aimed to investigate the efficacy and safety of RTX in patients with membranous nephropathy.
METHODS
A literature search was performed using Pubmed, Embase, OVID, and Cochrane Library and randomized controlled trials (RCTs) case-controls and cohort studies published till 30 July 2019 were assessed. The studies assessing the efficacy and safety of RTX in patients with membranous nephropathy were included.
RESULTS
Eight relevant trials involving 542 patients were included in the meta-analysis. It was found that RTX did not significantly improve serum albumin levels and e-GFR when compared with the control group (including cyclosporine and cyclophosphamide, chlorambucil, prednisone, non-immunosuppressive anti-proteinuria treatment), serum albumin levels (OR = 0.31, 95%CI-0.12-0.74, P = .15), e-GFR (OR = -1.49, 95%CI-17.14-14.17, P = .85). However, RTX did reduce the serum creatinine (OR = -0.01, 95%CI-0.36-0.34, P = .95) and urinary protein (OR = -2.39, 95%CI -7.30 -2.53, P = .34) levels. Also, in comparison to the control group, RTX did improve the total remission rate (OR = 1.63, 95%CI 0.48-5.54, P = .43), achieve a higher rate of complete remission (OR = 2.54, 95%CI 1.65-3.90, P < .01) and also reduced the amount of M-type phospholipase A2 receptor-Antibody depletion in patients (OR = 5.59, 95%CI 1.81-17.2, P = .003). RTX-related adverse events were mostly mild (most infusion-related reactions) in nature and serious adverse events were rare.
CONCLUSION
RTX proved to be efficient, well-tolerated and a safe drug in the treatment of membranous nephropathy. Most patients reach complete remission during the follow-up period, and relapse is rare. RTX may turn out to be promising in membranous nephropathy patients.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Case-Control Studies; Chlorambucil; Cyclophosphamide; Cyclosporine; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisone; Proteinuria; Randomized Controlled Trials as Topic; Receptors, Phospholipase A2; Remission Induction; Rituximab; Safety; Serum Albumin; Treatment Outcome
PubMed: 32311997
DOI: 10.1097/MD.0000000000019804 -
International Urology and Nephrology Oct 2023Membranous nephropathy is an autoimmune nephropathy that is one of the most common pathological types of nephrotic syndrome. It is important to find and apply specific... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Membranous nephropathy is an autoimmune nephropathy that is one of the most common pathological types of nephrotic syndrome. It is important to find and apply specific biomarkers for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, there are limited data about their diagnostic value. Therefore, an overall meta-analysis helps to identify effective biomarkers for the clinical diagnosis of IMN.
METHODS
A systematic literature search was carried out in PubMed, Embase, Cochrane and Web of Science from inception until December 31, 2020. Two researchers searched for studies that met the inclusion criteria. The results of the joint study were expressed in terms of sensitivity and specificity.
RESULTS
The meta-analysis included 24 studies with biomarkers for the clinical diagnosis of IMN, including antibody against phospholipase A2 receptor (PLAR-AB), antibody against thrombospondin type I domain-containing 7A (THSD7A-AB), lysosome membrane protein-2 (LIMP-2) and circular RNAs. The diagnostic efficiency of PLAR-AB for IMN had a combined sensitivity of 60% and a combined specificity of 100%. The diagnostic efficiency of THSD7A-AB for IMN had a combined sensitivity of 3% and a combined specificity of 99%. The diagnostic efficiency of urinary LIMP-2 for IMN was 100%, and the specificity was 100%. The diagnostic efficiency of exosomal circRNAs for IMN was 100%, and the specificity was 100%.
CONCLUSIONS
This meta-analysis shows that PLAR-AB and THSD7A-AB are of important diagnostic value for IMN. More studies are needed in the future to reveal the diagnostic value of LIMP-2 and circRNAs for IMN.
Topics: Humans; Glomerulonephritis, Membranous; RNA, Circular; Autoantibodies; Biomarkers; Polyesters; Receptors, Phospholipase A2
PubMed: 36961513
DOI: 10.1007/s11255-023-03561-w -
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 -
Nutrition Reviews Jul 2023Dietary fatty acids (FAs), primarily n-3 polyunsaturated FAs, have been associated with enrichment of the circulating bioactive lipidome and changes in the enzymatic... (Meta-Analysis)
Meta-Analysis
The effects of fatty acid-based dietary interventions on circulating bioactive lipid levels as intermediate biomarkers of health, cardiovascular disease, and cardiovascular disease risk factors: a systematic review and meta-analysis of randomized clinical trials.
CONTEXT
Dietary fatty acids (FAs), primarily n-3 polyunsaturated FAs, have been associated with enrichment of the circulating bioactive lipidome and changes in the enzymatic precursor lipoprotein-associated phospholipase A2 (Lp-PLA2) mass; however, the magnitude of this effect remains unclear.
OBJECTIVE
The aim of this systematic review and meta-analysis was to evaluate the effect of different dietary FAs on the bioactive lipid profile of healthy participants and those with cardiovascular disease (CVD) and CVD risk factors.
DATA SOURCES
PubMed, SCOPUS and the Cochrane Library databases were searched for relevant articles published between October 2010 and May 2022.
DATA EXTRACTION
Data were screened for relevance and then retrieved in full and evaluated for eligibility by 2 reviewers independently.
DATA ANALYSIS
The net difference in the bioactive lipid mean values between the endpoint and the baseline, and the corresponding SDs or SEs, were used for the qualitative synthesis. For the meta-analysis, a fixed-effects model was used.
RESULTS
Twenty-seven randomized clinical trials (representing >2560 participants) were included. Over 78% of the enrolled participants had ≥1 associated CVD risk factor, whereas <22% were healthy. In the meta-analysis, marine n-3 supplements (dose range, 0.37-1.9 g/d) significantly increased pro-inflammatory lysophosphatidylcholines (lyso-PCs; for lyso-PC(16:0): mean, +0.52 [95% confidence interval (CI), 0.02-1.01] µM; for lyso-PC(18:0): mean, +0.58 [95%CI, 0.09-1.08] µM) in obese participants. Additionally, n-3 supplementation (1-5.56 g/d) decreased plasma Lp-PLA2 mass, a well-known inflammation marker, in healthy (-0.35 [95%CI, -0.59 to -0.10] ng/mL), dyslipidemic (-0.36 [95%CI, -0.47 to -0.25] ng/mL), and stable coronary artery disease participants (-0.52 [95%CI, -0.91 to -0.12] ng/mL).
CONCLUSIONS
Daily n-3 provided as EPA+DHA supplements and consumed from 1 to 6 months reduced plasma Lp-PLA2 mass in healthy participants and those with CVD and CVD risk factors, suggesting an anti-inflammatory effect. However, the saturated lyso-PC response to n-3 was impaired in obese participants.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42021218335.
Topics: Humans; 1-Alkyl-2-acetylglycerophosphocholine Esterase; Biomarkers; Cardiovascular Diseases; Fatty Acids; Obesity; Randomized Controlled Trials as Topic; Lipids
PubMed: 36545749
DOI: 10.1093/nutrit/nuac101