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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 -
Neuropsychopharmacology : Official... Jan 2017This paper describes the effects of immune genes genetic variants and mRNA expression on depression's risk, severity, and response to antidepressant treatment, through a... (Review)
Review
This paper describes the effects of immune genes genetic variants and mRNA expression on depression's risk, severity, and response to antidepressant treatment, through a systematic review on all papers published between 2000 and 2016. Our results, based largely on case-control studies, suggest that common genetic variants and gene-expression pathways are involved in both immune activation and depression. The most replicated and relevant genetic variants include polymorphisms in the genes for interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, C-reactive protein, and phospholipase A2. Moreover, increased blood cytokines mRNA expression (especially of IL-1β) identifies patients that are less likely to respond to conventional antidepressants. However, even for the most replicated findings there are inconsistent results, not only between studies, but also between the immune effects of the genetic variants and the resulting effects on depression. We find evidence that these discrepant findings may be explained, at least in part, by the heterogeneity of the depression immunophenotype, by environmental influences and gene × environment interactions, and by the complex interfacing of genetic variants with gene expression. Indeed, some of the most robust findings have been obtained in patients developing depression in the context of treatment with interferon-alpha, a widely used model to mimic depression in the context of inflammation. Further 'omics' approaches, through GWAS and transcriptomics, will finally shed light on the interaction between immune genes, their expression, and the influence of the environment, in the pathogenesis of depression.
Topics: Cytokines; Depressive Disorder; Humans; Inflammation
PubMed: 27555379
DOI: 10.1038/npp.2016.169 -
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 -
Arab Journal of Urology 2019: To review and present the most distinct concepts on the association of reactive oxygen species (ROS) with male reproduction. : The Preferred Reporting Items for... (Review)
Review
: To review and present the most distinct concepts on the association of reactive oxygen species (ROS) with male reproduction. : The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines were used to search PubMed, Medline, EMBASE, and the Cochrane electronic databases for studies investigating the role of oxidative stress (OS) on sperm function. : The literature search yielded 1857 studies, of which 1791 articles were excluded because of irrelevance of data, non-English language, non-human nature or because they were case reports or commentaries. All included studies were reviews (46), meta-analyses (one), original research studies (18) and guideline articles (one). The studies were published between 1984 and 2018. Under normal physiological conditions, ROS are vital for sperm maturation, hyperactivation, capacitation, acrosome reaction, as well as fertilisation. However, a number of endogenous and exogenous causes may induce supra-physiological levels of ROS resulting in lipid peroxidation, sperm DNA fragmentation and apoptosis, and consequently infertility. Several laboratory testing methods can be used in infertile men to diagnose OS. Treatment usually involves antioxidant supplementation and, when possible, elimination of the causative factor. : OS is an important cause of male factor infertility. Its assessment provides essential information that can guide treatment strategies aimed at improving the male's reproductive potential. bp: base-pair; CAT: catalase; LPO: lipid peroxidation; MDA: malondialdehyde; MiOXSYS: Male Infertility Oxidative System; mtDNA: mitochondrial DNA; NAD(PH): nicotinamide adenine dinucleotide (phosphate); NO: nitric oxide; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; ORP: oxidation-reduction potential; OS: oxidative stress; PKA: protein kinase A; PLA2: phospholipase A2; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PUFA: poly-unsaturated fatty acid; ROS: reactive oxygen species; SOD: superoxide dismutase; TAC: total antioxidant capacity; TBA: thiobarbituric acid.
PubMed: 31285919
DOI: 10.1080/2090598X.2019.1599624 -
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 -
Pharmaceuticals (Basel, Switzerland) Mar 2010The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are... (Review)
Review
The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are generally administered to acute pancreatitis patients upon admission to the hospital. In addition, these drugs have also been used to prevent post-endoscopic cholangiopancreatography (ERCP) acute pancreatitis. On the other hand, there are several reports indicating that NSAIDs may be the actual cause of acute pancreatitis. We carried out a literature search on PubMed/MEDLINE; all full text papers published in from January 1966 to November 2009 on the use of NSAIDs in acute pancreatitis were collected; the literature search was also supplemented by a review of the bibliographies of the papers evaluated. Thus, in this article, we will systematically review the current literature in order to better illustrate the role of NSAIDs in acute pancreatitis, in particular: i) NSAIDs as a cause of acute pancreatitis; ii) their use to prevent post-retrograde ERCP pancreatitis and iii) their efficacy for pain relief in the acute illness of the pancreas.
PubMed: 27713268
DOI: 10.3390/ph3030558 -
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 -
Medicine Dec 2017Studies on stroke and lipoprotein-associated phospholipase A2 (Lp-PLA2) have produced conflicting results. (Meta-Analysis)
Meta-Analysis Review
The associations of stroke, transient ischemic attack, and/or stroke-related recurrent vascular events with Lipoprotein-associated phospholipase A2: A systematic review and meta-analysis.
BACKGROUND
Studies on stroke and lipoprotein-associated phospholipase A2 (Lp-PLA2) have produced conflicting results.
OBJECTIVE
The aim of the study was to assess the associations of Lp-PLA2 levels (mass and activity) with recurrent vascular events in patients with transient ischemic attack (TIA) and/or first ischemic stroke and with stroke in the general population.
METHODS
The MEDLINE, Embase, the Cochrane Library, Web of Science, Science Direct, China National Knowledge Infrastructure, China Biology Medical Disc (CBMdisc), and WanFang were searched for prospective observational studies reported until January 2017. Eligible studies reported Lp-PLA2 levels and adjusted risk estimates of recurrent vascular events and/or stroke. Risk ratio (RR) with corresponding 95% confidence intervals (CIs) were used to express the pooled data in a random-effects model.
RESULTS
A total of 11 studies that comprised 20,284 participants (4,045 were TIA and/or first ischemic stroke patients and 16,239 were residents in general population) were identified, which reported either Lp-PLA2 mass levels (4 studies) or Lp-PLA2 activity levels (10 studies). The pooled RR of recurrent vascular events (467 cases) in TIA and/or first ischemic group was 2.24 (95% CI, 1.33-3.78), whereas the pooled RR of stroke (1604 cases) in the general population was 1.47 (95% CI, 1.10-1.97). The pooled RRs of Lp-PLA2 mass and activity levels with the risk of stroke in the general population were 1.69 (95% CI, 1.03-2.79) and 1.28 (95% CI, 0.88-1.85), respectively.
CONCLUSIONS
In patients with TIA and first ischemic stroke, elevated Lp-PLA2 activity levels were associated with recurrent vascular events. And in the general population elevated Lp-PLA2 levels were associated with the risk of stroke, although the association between Lp-PLA2 activity levels and the risk of stroke was less profound compared with the corresponding association of stroke risk with the Lp-PLA2 mass levels.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Humans; Ischemic Attack, Transient; Recurrence; Stroke
PubMed: 29390564
DOI: 10.1097/MD.0000000000009413 -
International Journal of Molecular... Mar 2023Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain... (Review)
Review
Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.
Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain connectivity. Antipsychotics are the primary pharmacological treatment after more than sixty years after their introduction in therapy. Two findings hold true for all presently available antipsychotics. First, all antipsychotics occupy the dopamine D2 receptor (D2R) as an antagonist or partial agonist, even if with different affinity; second, D2R occupancy is the necessary and probably the sufficient mechanism for antipsychotic effect despite the complexity of antipsychotics' receptor profile. D2R occupancy is followed by coincident or divergent intracellular mechanisms, implying the contribution of cAMP regulation, β-arrestin recruitment, and phospholipase A activation, to quote some of the mechanisms considered canonical. However, in recent years, novel mechanisms related to dopamine function beyond or together with D2R occupancy have emerged. Among these potentially non-canonical mechanisms, the role of Na channels at the dopamine at the presynaptic site, dopamine transporter (DAT) involvement as the main regulator of dopamine concentration at synaptic clefts, and the putative role of antipsychotics as chaperones for intracellular D2R sequestration, should be included. These mechanisms expand the fundamental role of dopamine in schizophrenia therapy and may have relevance to considering putatively new strategies for treatment-resistant schizophrenia (TRS), an extremely severe condition epidemiologically relevant and affecting almost 30% of schizophrenia patients. Here, we performed a critical evaluation of the role of antipsychotics in synaptic plasticity, focusing on their canonical and non-canonical mechanisms of action relevant to the treatment of schizophrenia and their subsequent implication for the pathophysiology and potential therapy of TRS.
Topics: Humans; Antipsychotic Agents; Dopamine; Schizophrenia; Schizophrenia, Treatment-Resistant; beta-Arrestins
PubMed: 36983018
DOI: 10.3390/ijms24065945 -
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