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Disease Markers 2019Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS)... (Review)
Review Meta-Analysis
Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS) leads to substantial deficits of sensory, motor, autonomic, and neurocognitive functions. Considering all genetic studies on MS, including the advanced genome-wide association studies, the risk linked to HLA alleles remains the highest among other susceptibility genetic variants. However, given the genetic variability of HLA alleles in different ethnic groups, we conducted a systematic review of reviews and meta-analyses aiming at summarizing all the results on the association between MS and HLA class II genes. We systematically searched meta-analyses and systematic reviews dealing with MS and HLA in all ethnicities. From 154 records, we included 5 articles collecting HLA data from 15,232 MS patients and 24,194 ethnically matched controls. DRB1∗15 (OR ranging from 1.39 in Chinese Han to 2.59 in Caucasians) and DQB1∗06:02 (OR ranging from 1.91 in Caucasians to 2.49 in Colombian) alleles confer an increased risk for MS transethnically (Caucasians, Chinese, South Americans, Carribeans, Middle Easterners, Japanese, and North Africans). DRB1∗01, DRB1∗09, DRB1∗11, DRB1∗12, and DRB1∗16 alleles were protective, in agreement with the type of amino-acidic (aa) residues (ranging from position 9 to 90) included in pockets 1, 4, 6, 7, and 9, which are most involved in peptide presentation. Changes in aa residues affect the capability of HLA molecules in binding myelin peptides. DQB1∗06:02 risk allele seems to be the most interesting target as humanized mice expressing only DQB1∗06:02 develop MS-like disease mediated by autoimmune reactions against myelin oligodendrocytic basic protein that stabilizes the myelin. Our summary of results from a high number of patients and controls suggests that allelic variants from both DQB1 and DRB1 genes are equally involved in MS susceptibility/protection transethnically.
Topics: Alleles; Animals; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA-DQ beta-Chains; HLA-DRB1 Chains; Humans; Multiple Sclerosis; Risk Factors
PubMed: 31781296
DOI: 10.1155/2019/1409069 -
Current Radiopharmaceuticals 2020Radiolabeled prostate-specific membrane antigen PSMA-based PET/CT or PET/MRI is a whole-body imaging technique currently performed for the detection of prostate cancer...
BACKGROUND
Radiolabeled prostate-specific membrane antigen PSMA-based PET/CT or PET/MRI is a whole-body imaging technique currently performed for the detection of prostate cancer lesions. PSMA has been also demonstrated to be expressed by the neovasculature of many other solid tumors.
OBJECTIVE
The aim of this review is to evaluate the possible diagnostic role of radiolabeled PSMA PET/CT or PET/MRI in patients with gliomas and glioblastomas, by summarizing the available literature data.
METHODS
A comprehensive literature search of the PubMed/MEDLINE, Scopus, Embase and Cochrane library databases was conducted to find relevant published articles about the diagnostic performance of radiolabeled PSMA binding agents in PET/CT or PET/MRI imaging of patients with suspected gliomas or glioblastomas.
RESULTS
Seven case reports or case series and 3 studies enrolling more than 10 patients showed that gliomas and glioblastoma are PSMA-avid tumors.
CONCLUSION
Radiolabeled PSMA imaging seems to be useful in analyzing glioma/glioblastoma. Further studies enrolling a wider population are needed to clarify the real clinical and diagnostic role of radiolabeled PSMA in this setting and its possible position in the diagnostic flow-chart.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Magnetic Resonance Imaging; Male; Multimodal Imaging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostate-Specific Antigen; Radiopharmaceuticals; Whole Body Imaging
PubMed: 31625482
DOI: 10.2174/1874471012666191017093721 -
BMC Medical Genomics Sep 2019Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD).
METHODS
We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis.
RESULTS
We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04-2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18-2·66) and none of the outcome polymorphisms.
CONCLUSIONS
Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.
Topics: Disease Susceptibility; Humans; Lipopolysaccharide Receptors; Mannose-Binding Lectin; Odds Ratio; Phenotype; Pneumococcal Infections; Polymorphism, Genetic; RNA, Long Noncoding; Risk Factors
PubMed: 31519222
DOI: 10.1186/s12920-019-0572-x -
Discovery Medicine Jul 2019Circulating exosomal microRNAs modulate not only cancer cell metabolism but also the immune response, and therefore plasma exosomal microRNAs might have the potential to...
Novel findings from determination of common expressed plasma exosomal microRNAs in patients with psoriatic arthritis, psoriasis vulgaris, rheumatoid arthritis, and gouty arthritis.
BACKGROUND
Circulating exosomal microRNAs modulate not only cancer cell metabolism but also the immune response, and therefore plasma exosomal microRNAs might have the potential to be the biomarkers for a number of immune disorders.
OBJECTIVE
This study was conducted to identify the common mechanisms among psoriatic arthritis (PsA), psoriasis vulgaris (PV), rheumatoid arthritis (RA), and gouty arthritis (GA). The common expressed plasma exosomal microRNAs in these diseases were determined.
METHODS
The expression of microRNAs derived from plasma exosome of patients with PsA (n=30), PV (n=15), RA (n=15), GA (n=15), and healthy controls (n=15) was evaluated via sequencing. Function analysis of common expressed microRNAs was conducted by the Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Coexpression analysis was conducted to identify novel and significant genes and proteins by using the Search Tool for the Retrieval of Interacting Genes (STRING). A systematic literature review was conducted to uncover the role of the common microRNAs in the pathogenesis of PsA, PV, RA, and GA.
RESULTS
A total of 36 common expressed microRNAs were detected in patients with PsA, PV, RA, and GA. The most significantly enriched biological processes, cellular components, and molecular functions were "homophilic cell adhesion via plasma membrane adhesion molecules," "CCR4-NOT complex," and "calcium ion binding," respectively. "Antigen processing and presentation" was the most significantly enriched pathway. A total of 91 validated coexpressed gene pairs were identified and 16 common expressed microRNAs and 85 potential target genes were screened based on Cytoscape. Of 36 common expressed microRNAs, 5 microRNAs, including hsa-miR-151a-3p, hsa-miR-199a-5p, hsa-miR-370-3p, hsa-miR-589-5p, and hsa-miR-769-5p, were considered to be connected with the common pathogenesis of PsA, PV, RA, and GA. Systemic review revealed that the roles of these 5 microRNAs are related to immune disorder and bone injury, which matches the conclusion from GO and KEGG analyses.
CONCLUSION
(1) Both immune disorder and bone metabolic dysregulation could be the shared mechanism in the development of PsA, PV, RA, and GA. (2) Immune dysfunction is involved in GA. Our study may shed new light on the diagnosis and treatment strategy of these autoimmune diseases and GA, which warrants further studies.
Topics: Adult; Aged; Arthritis, Gouty; Arthritis, Psoriatic; Arthritis, Rheumatoid; Female; Gene Expression Regulation; Humans; Male; MicroRNAs; Middle Aged
PubMed: 31465725
DOI: No ID Found -
International Journal of Molecular... Aug 2019L1 cell adhesion molecule (L1CAM) is a glycoprotein involved in cancer development and is associated with metastases and poor prognosis. Cellular processing of L1CAM...
L1 cell adhesion molecule (L1CAM) is a glycoprotein involved in cancer development and is associated with metastases and poor prognosis. Cellular processing of L1CAM results in expression of either full-length or cleaved forms of the protein. The different forms of L1CAM may localize at the plasma membrane as a transmembrane protein, or in the intra- or extracellular environment as cleaved or exosomal forms. Here, we systematically analyze available literature that directly relates to L1CAM domains and associated signaling pathways in cancer. Specifically, we chart its domain-specific functions in relation to cancer progression, and outline pre-clinical assays used to assess L1CAM. It is found that full-length L1CAM has both intracellular and extracellular targets, including interactions with integrins, and linkage with ezrin. Cellular processing leading to proteolytic cleavage and/or exosome formation results in extracellular soluble forms of L1CAM that may act through similar mechanisms as compared to full-length L1CAM, such as integrin-dependent signals, but also through distinct mechanisms. We provide an algorithm to guide a step-wise analysis on L1CAM in clinical samples, to promote interpretation of domain-specific expression. This systematic review infers that L1CAM has an important role in cancer progression that can be attributed to domain-specific forms. Most studies focus on the full-length plasma membrane L1CAM, yet knowledge on the domain-specific forms is a prerequisite for selective targeting treatment.
Topics: Animals; Biomarkers; Carrier Proteins; Cell Adhesion; Cell Transformation, Neoplastic; Humans; Neoplasms; Neural Cell Adhesion Molecule L1; Protein Binding; Protein Interaction Domains and Motifs; Signal Transduction
PubMed: 31455004
DOI: 10.3390/ijms20174180 -
Frontiers in Immunology 2019A systematic review and meta-analysis of diagnostic biomarkers for noninvasive diagnosis of acute allograft rejection following liver transplantation. Noninvasive... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of diagnostic biomarkers for noninvasive diagnosis of acute allograft rejection following liver transplantation. Noninvasive blood and urine markers have been widely explored in recent decades for diagnosing acute rejection after liver transplantation. However, none have been translated into routine clinical use so far due to uncertain diagnostic accuracy, and liver biopsy remains the gold standard. Systematic literature searches of Medline, Cochrane and Embase were conducted up to February 2019 to identify studies evaluating the use of noninvasive markers in diagnosing allograft rejection following liver transplantation. Meta-analysis was performed using a random effects model with DerSimonian-Laird weighting and the hierarchical summary receiver operating curve. Of 560 identified studies, 15 studies (1,445 patients) met the inclusion criteria. The following markers were tested: acid labile nitroso-compounds (NOx), serum amyloid A protein, procalcitonin, peripheral blood eosinophil count, peripheral blood T-cell activation and interleukin 2 (IL-2) receptor, guanylate-binding protein-2 mRNA, graft-derived cell-free DNA, pi-glutathione S-transferase, alpha-glutathione S-transferase and serum HLA class I soluble antigens. Only eosinophil count was tested in multiple studies, and they demonstrated high heterogeneity ( = 72% [95% CI: 0.5-0.99]). IL-2 receptor demonstrated the highest sensitivity (89% [95% CI: 0.78-0.96]) and specificity (81% [95% CI: 0.69-0.89]). IL-2 receptor expression demonstrated the highest diagnostic accuracy, while the peripheral eosinophil count was the only marker tested in more than one study. Presently, liver biopsy remains superior to noninvasive diagnostic biomarkers as most studies exhibited inferior designs, hindering possible translation into clinical application.
Topics: Acute Disease; Biomarkers; Biopsy; Diagnostic Errors; Eosinophils; Graft Rejection; Humans; Leukocyte Count; Liver; Liver Transplantation; Receptors, Interleukin-2; Sensitivity and Specificity; Transplantation, Homologous
PubMed: 31031758
DOI: 10.3389/fimmu.2019.00758 -
Future Oncology (London, England) Dec 2018In September 2017, the US FDA announced re-approval of gemtuzumab ozogamicin (GO), a CD33-targeting immunoconjugate, for treatment of newly diagnosed and... (Meta-Analysis)
Meta-Analysis
In September 2017, the US FDA announced re-approval of gemtuzumab ozogamicin (GO), a CD33-targeting immunoconjugate, for treatment of newly diagnosed and relapsed/refractory acute myeloid leukemia (AML). This is a very significant step toward defining new treatment regimens in AML, as the treatment has essentially stayed unchanged with the '7 + 3 induction regimen' (7 days cytarabine and 3 days of anthracycline) since 1973. GO is the first antibody-drug conjugate to receive FDA approval for treating cancer. This review article discusses the challenges faced and lessons learned during the journey of GO for AML treatment. Selected trials that have made significant contribution in our understanding of the most efficacious and safe use of GO for treating AML patients as well as factors influencing GO response are highlighted in this article.
Topics: Age Factors; Aminoglycosides; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Drug Discovery; France; Gemtuzumab; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Randomized Controlled Trials as Topic; Sialic Acid Binding Ig-like Lectin 3; Treatment Outcome; United States
PubMed: 30039981
DOI: 10.2217/fon-2018-0325 -
BMC Infectious Diseases Jun 2018Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms of infection. While the vast majority (> 80%) of both dengue and West Nile virus infections result in asymptomatic infections, a minority of individuals experience symptomatic infection and an even smaller proportion develop severe disease. The mechanisms by which these infections lead to severe disease in a subset of infected individuals is incompletely understood, but individual host differences including genetic factors and immune responses have been proposed. We sought to identify genetic risk factors that are associated with more severe disease outcomes for both viruses in order to shed light on possible shared mechanisms of resistance and potential therapeutic interventions.
METHODS
We applied a search strategy using four major databases (Medline, PubMed, Embase, and Global Health) to find all known genetic associations identified to date with dengue or West Nile virus disease. Here we present a review of our findings and a meta-analysis of genetic variants identified.
RESULTS
We found genetic variations that are significantly associated with infections of these viruses. In particular we found variation within the OAS1 (meta-OR = 0.83, 95% CI: 0.69-1.00) and CCR5 (meta-OR = 1.29, 95% CI: 1.08-1.53) genes is significantly associated with West Nile virus disease, while variation within MICB (meta-OR = 2.35, 95% CI: 1.68-3.29), PLCE1 (meta-OR = 0.55, 95% CI: 0.42-0.71), MBL2 (meta-OR = 1.54, 95% CI: 1.02-2.31), and IFN-γ (meta-OR = 2.48, 95% CI: 1.30-4.71), is associated with dengue disease.
CONCLUSIONS
Despite substantial heterogeneity in populations studied, genes examined, and methodology, significant associations with genetic variants were found across studies within both diseases. These gene associations suggest a key role for immune mechanisms in susceptibility to severe disease. Further research is needed to elucidate the role of these genes in disease pathogenesis and may reveal additional genetic factors associated with disease severity.
Topics: 2',5'-Oligoadenylate Synthetase; Dengue; Genetic Predisposition to Disease; Histocompatibility Antigens Class I; Humans; Interferon-gamma; Mannose-Binding Lectin; Phosphoinositide Phospholipase C; Receptors, CCR5; West Nile Fever
PubMed: 29929468
DOI: 10.1186/s12879-018-3186-6 -
Cartilage Jan 2019Osteoarthritis (OA) is one of the leading causes of disability in the adult population. Common nonoperative treatment options include nonsteroidal anti-inflammatory...
OBJECTIVE
Osteoarthritis (OA) is one of the leading causes of disability in the adult population. Common nonoperative treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular corticosteroids, and intra-articular injections of hyaluronic acid (HA). HA is found intrinsically within the knee joint providing viscoelastic properties to the synovial fluid. HA therapy provides anti-inflammatory relief through a number of different pathways, including the suppression of pro-inflammatory cytokines and chemokines.
METHODS
We conducted a systematic review to summarize the published literature on the anti-inflammatory properties of hyaluronic acid in osteoarthritis. Included articles were categorized based on the primary anti-inflammatory responses described within them, by the immediate cell surface receptor protein assessed within the article, or based on the primary theme of the article. Key findings aimed to describe the macromolecules and inflammatory-mediated responses associated with the cell transmembrane receptors.
RESULTS
Forty-eight articles were included in this systematic review that focused on the general anti-inflammatory effects of HA in knee OA, mediated through receptor-binding relationships with cluster determinant 44 (CD44), toll-like receptor 2 (TLR-2) and 4 (TLR-4), intercellular adhesion molecule-1 (ICAM-1), and layilin (LAYN) cell surface receptors. Higher molecular weight HA (HMWHA) promotes anti-inflammatory responses, whereas short HA oligosaccharides produce inflammatory reactions.
CONCLUSIONS
Intra-articular HA is a viable therapeutic option in treating knee OA and suppressing inflammatory responses. HMWHA is effective in suppressing the key macromolecules that elicit the inflammatory response by short HA oligosaccharides.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Hyaluronan Receptors; Hyaluronic Acid; Injections, Intra-Articular; Intercellular Adhesion Molecule-1; Knee Joint; Lectins, C-Type; Male; Osteoarthritis, Knee; Synovial Fluid; Toll-Like Receptor 2; Toll-Like Receptor 4; Treatment Outcome; Viscosupplements
PubMed: 29429372
DOI: 10.1177/1947603517749919 -
ESC Heart Failure May 2017Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared... (Review)
Review
Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared biomarkers representing common pathogenic pathways between heart failure with preserved ejection fraction (HFpEF) and pre-eclampsia where these biomarkers might be potentially eligible for cardiovascular risk stratification in women after hypertensive pregnancy disorders. We sought for blood markers in women with diastolic dysfunction in a first literature search, and through a second search, we investigated whether these same biochemical markers were present in pre-eclampsia.This systematic review and meta-analysis presents two subsequent systematic searches in PubMed and EMBASE. Search I yielded 3014 studies on biomarkers discriminating women with HFpEF from female controls, of which 13 studies on 11 biochemical markers were included. Cases had HFpEF, and controls had no heart failure. The second search was for studies discriminating women with pre-eclampsia from women with non-hypertensive pregnancies with at least one of the biomarkers found in Search I. Search II yielded 1869 studies, of which 51 studies on seven biomarkers were included in meta-analyses and 79 studies on 12 biomarkers in systematic review.Eleven biological markers differentiated women with diastolic dysfunction from controls, of which the following 10 markers differentiated women with pre-eclampsia from controls as well: C-reactive protein, HDL, insulin, fatty acid-binding protein 4, brain natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin, mid-region pro adrenomedullin, cardiac troponin I, and cancer antigen 125.Our study supports the hypothesis that HFpEF in women shares a common pathogenic background with pre-eclampsia. The biomarkers representing inflammatory state, disturbances in myocardial function/structure, and unfavourable lipid metabolism may possibly be eligible for future prognostic tools.
PubMed: 28451444
DOI: 10.1002/ehf2.12129