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Medicine Mar 2017Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10%... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10% to 30% of patients discontinue therapy within a year of starting the treatment, usually because of undesirable side effects. Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX toxicity in RA patients, although inconsistent results have been reported.
METHODS
We searched EMBASE and PubMed in February 2016 for polymorphisms and pharmacogenomics study of the toxicity of MTX monotherapy in RA patients. The meta-analysis was stratified by whether genetic variants associated with MTX toxicity.
RESULTS
A total of 42 publications that included 28 genes with 88 gene SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the SR, and 31 studies were included in 7 meta-analyses. The meta-analysis showed a significant association between the toxicity of MTX and the RFC-1 80G > A (rs1051266) polymorphism in the European RA patients.
CONCLUSION
RFC-1 80G > A (rs1051266) polymorphism was associated with MTX toxicity, and larger and more stringent study designs may provide more accurate results for the effect of these SNPs on the MTX toxicity.
Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; ATP Binding Cassette Transporter, Subfamily B; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Ferredoxin-NADP Reductase; Humans; Hydroxymethyl and Formyl Transferases; Methotrexate; Methylenetetrahydrofolate Reductase (NADPH2); Multienzyme Complexes; Nucleotide Deaminases; Pharmacogenetics; Polymorphism, Single Nucleotide; Replication Protein C
PubMed: 28296761
DOI: 10.1097/MD.0000000000006337 -
Arquivos de Neuro-psiquiatria Jan 2023Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent...
BACKGROUND
Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR).
OBJECTIVES
To realize a systematic literature review to determine the impact of genetic variants on AR.
METHODS
Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included.
RESULTS
The genetic variants rs1126643 (), rs3842787 (), rs20417 (), and rs5918 () were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance ( < 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (), rs1045642 (), rs1051931 and rs7756935 (), rs2071746 (), rs1131882 and rs4523 (), rs434473 (), rs9315042 (), and rs662 (), while these differ in real interference in AR: rs5918 (), rs2243093 (), rs1330344 (), and rs20417 (). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences.
CONCLUSION
It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.
Topics: Humans; Aspirin; Cardiovascular Diseases; Cyclooxygenase 2; Pharmacogenetics; Platelet Aggregation Inhibitors; Drug Resistance
PubMed: 36918009
DOI: 10.1055/s-0042-1758445 -
Medicine Jan 2020Leigh syndrome (also called Leigh disease or subacute necrotizing encephalomyelopathy) is a rare inherited neurometabolic disorder, which affects the central nervous... (Meta-Analysis)
Meta-Analysis
Leigh syndrome (also called Leigh disease or subacute necrotizing encephalomyelopathy) is a rare inherited neurometabolic disorder, which affects the central nervous system. This meta-study systematically analyzed clinical manifestations, respiratory chain enzyme complex deficiency, and gene mutations.Literature was searched for publications in MEDLINE, EMBASE, and the China National Knowledge Infrastructure database for meta-analyses of the incidence of clinical symptoms, laboratory assessments, imaging data, muscle biopsy histochemical staining, activity of the mitochondrial respiratory chain enzyme complex, gene mutations, and the association between age at disease onset and type of gene mutations.This study included 5 studies with 385 Leigh syndrome patients. The most common clinical features of Leigh syndrome included elevated blood and/or cerebrospinal fluid (CSF) levels of lactate (72%), developmental retardation (57%), hypotonia (42%), followed by respiratory dysfunction (34%), epileptic seizures (33%), poor feeding (29%), and weakness (27%). Approximately 80% of the patients had deficiencies of the respiratory chain enzyme complex or isolated complex I deficiency (35%), 32% had mitochondrial DNA (mtDNA) mutations, and 38% had nuclear DNA (nDNA) mutations. Patients with nDNA mutations were younger than those with mtDNA mutations (8.82 ± 13.88 vs 26.20 ± 41.11 years, P = .007).The data from the current meta-analysis demonstrated a variety of clinical and molecular manifestations of Leigh syndrome, with upregulated lactate levels in the blood or CSF being the most common feature. Diagnosis of Leigh syndrome could be confirmed using combined enzymatic and genetic analyses.
Topics: Electron Transport Complex I; Humans; Leigh Disease; Mutation
PubMed: 32000367
DOI: 10.1097/MD.0000000000018634 -
The Turkish Journal of Gastroenterology... Nov 2021Pancreatic ductal adenocarcinoma (PDAC) is deadly cancer with a poor prognosis. Molecular prognostic markers are needed to predict the patient's survival. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is deadly cancer with a poor prognosis. Molecular prognostic markers are needed to predict the patient's survival. The cyclooxygenase-2 enzyme (COX-2) and its 2 major transcription factors--nuclear factorkappa B (NF-κB) and specificity protein 1 (Sp1)--are activated during inflammation caused by neoplasia. Several studies have investigated the association between the COX-2, NF-κB, and Sp1 tissue expressions with the patient's overall survival. Therefore, we conducted this systematic review and meta-analysis to evaluate those studies.
METHODS
We searched for relevant articles from the MEDLINE database through June 2020. Studies were eligible if they included dichotomized tissue protein expression status and the overall survival as the outcome. We used RevMan and ProMeta programs to perform the meta-analysis.
RESULTS
We identified 11 eligible studies. The meta-analysis showed that COX-2 tissue expression was associated with decreased overall survival (crude HR = 1.35; 95% CI, 1.05-1.74), although the result was not significant when controlling for other covariates. The NF-κB tissue expression was associated with decreased overall survival (crude HR = 2.18; 95% CI, 1.49-3.18), although it was not significant when controlling for other covariates. The Sp1 tissue expression showed significantly decreased overall survival even when adjusted with other covariates (aHR = 3.47; 95% CI, 1.52-7.94). The limitations included searching only for English publications and the substantial heterogeneity among the studies.
CONCLUSION
COX-2, NF-κB, and Sp1 tissue expressions have the potential to be used as prognostic markers in PDAC. Further studies are still needed to clarify the associations.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Cyclooxygenase 2; Humans; NF-kappa B; Pancreatic Neoplasms; Prognosis; Sp1 Transcription Factor; Tissue Distribution
PubMed: 34872897
DOI: 10.5152/tjg.2021.211106 -
Medicine Sep 2022The cyclooxygenase-2 (COX-2) selective inhibitor parecoxib is widely used in the treatment of pain and inflammation. Parecoxib has been adopted for use for postoperative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The cyclooxygenase-2 (COX-2) selective inhibitor parecoxib is widely used in the treatment of pain and inflammation. Parecoxib has been adopted for use for postoperative analgesia following a range of surgical procedures (orthopedic, general, gynecological, and dental surgery). Total knee or total hip arthroplasty (THA) surgery is mostly done in older patients, so postoperative analgesics need to be used more carefully, and the safety and efficacy of parecoxib in this type of surgery need to be further verified. The aim of this study was to investigate the effects of parecoxib on patient safety, cumulative morphine consumption and was at 24 and 48 hours in the analgesic treatment of total knee or THA for meta-analysis and systematic review, with few studies in this area so far.
METHODS
We searched the Online Database Cochrane Library, PubMed, Web of Science, EMBASE, and CBM (SinoMed), CNKI, VIP, WANFANG up to January 2021. According to the value of I2, the random-effect model or fixed-effect model was supposed to combine data from studies, respectively. Publication bias was assessed through funneling plot and Beggs test. Review Manager 5.3 and Stata 16.0 software were applied to perform the statistical analyses.
RESULTS
Eleven RCTs which involved 1690 participants were included in this study. The meta-analysis indicated parecoxib sodium could not significantly reduce the incidence of adverse events after total knee or THA compared with placebo. There was no statistical significance in incidence of nausea and vomiting. 24 hours resting VAS score was statistically significant between the group. The 48-hour resting VAS scores did not indicate a significant difference between the groups.
CONCLUSION
Parecoxib can reduce the incidence of adverse events after total knee or total hip surgery to some extent but cannot reduce the incidence of nausea and vomiting. Twenty-four hour postoperative analgesia is better than placebo, but 48 hours after operation analgesia is the same as placebo.
Topics: Aged; Analgesics; Analgesics, Opioid; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Humans; Isoxazoles; Morphine; Nausea; Pain, Postoperative; Vomiting
PubMed: 36197263
DOI: 10.1097/MD.0000000000030748 -
Frontiers in Endocrinology 2024The leading indicator for successful outcomes in fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the... (Review)
Review
Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.
The leading indicator for successful outcomes in fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.
Topics: Humans; Male; Female; Cyclooxygenase 2; Cumulus Cells; Semen; Oocytes; Gene Expression; Intercellular Signaling Peptides and Proteins; Hyaluronan Synthases
PubMed: 38524634
DOI: 10.3389/fendo.2024.1274376 -
Molecules (Basel, Switzerland) Jul 2020Microalgae productive chains are gaining importance as sustainable alternatives to obtain natural pigments. This work presents a review on the most promising pigments...
Microalgae productive chains are gaining importance as sustainable alternatives to obtain natural pigments. This work presents a review on the most promising pigments and microalgal sources by gathering trends from a 10-year bibliometric survey, a patents search, and an industrial and market analysis built from available market reports, projects and companies' webpages. The performed analysis pointed out chlorophylls, phycocyanin, astaxanthin, and β-carotene as the most relevant pigments, and , , , and , respectively, as the most studied sources. is referred in the highest number of patents, corroborating a high technological interest in this microalga. The biorefinery concept, investment in projects and companies related to microalgae cultivation and/or pigment extraction is increasingly growing, particularly, for phycocyanin from . These pieces of evidence are a step forward to consolidate the microalgal pigments market, which is expected to grow in the coming years, increasing the prospects of replacing synthetic pigments by natural counterparts.
Topics: Drug Industry; Microalgae; Phycocyanin; Pigments, Biological
PubMed: 32731380
DOI: 10.3390/molecules25153406 -
Inflammation Research : Official... Jan 2019Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia...
BACKGROUND
Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia burgdorferi. The role of the inflammatory processes mediated by prostaglandins (PGs), thromboxanes and leukotrienes (LTs) in LB severity and symptoms resolution is yet to be elucidated.
OBJECTIVES
We aim to systematically review and evaluate the role of PGs and related lipid mediators in the induction and resolution of inflammation in LB.
METHODS
We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic to identify cell-culture, animal and human studies reporting the changes in PGs and related lipid mediators of inflammation during the course of LB.
RESULTS
We identified 18 studies to be included into this systematic review. The selected reports consisted of seven cell-culture studies, seven animal studies, and four human studies (from three patient populations). Results from cell-culture and animal studies suggest that PGs and other lipid mediators of inflammation are elevated in LB and may contribute to disease development. The limited number of human studies showed that subjects with Lyme meningitis, Lyme arthritis (LA) and antibiotic-refractory LA had increased levels of an array of PGs and lipid mediators (e.g., LTB 8-isoPGF, and phospholipases A activity). Levels of these markers were significantly reduced following the treatment with antibiotics or non-steroidal anti-inflammatory drugs.
CONCLUSION
Dysregulation of prostaglandins and related lipid mediators may play a role in the etiology of LB and persistence of inflammation that may lead to long-term complications. Further investigation into the precise levels of a wide range of PGs and related factors is critical as it may propose novel markers that can be used for early diagnosis.
Topics: Animals; Biomarkers; Humans; Lyme Disease; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Severity of Illness Index
PubMed: 30121835
DOI: 10.1007/s00011-018-1180-5 -
The Journal of Antimicrobial... Mar 2018Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in non-endemic countries and its prevention in travellers. Mutations in the cytochrome bc1 complex are causally associated with atovaquone resistance.
METHODS
This systematic review assesses the clinical efficacy of atovaquone/proguanil treatment of uncomplicated malaria and examines the extent to which codon 268 mutation in cytochrome b influences treatment failure and recrudescence based on published information.
RESULTS
Data suggest that atovaquone/proguanil treatment efficacy is 89%-98% for P. falciparum malaria (from 27 studies including between 18 and 253 patients in each case) and 20%-26% for Plasmodium vivax malaria (from 1 study including 25 patients). The in vitro P. falciparum phenotype of atovaquone resistance is an IC50 value >28 nM. Case report analyses predict that recrudescence in a patient presenting with parasites carrying cytochrome b codon 268 mutation will occur on average at day 29 (95% CI: 22, 35), 19 (95% CI: 7, 30) days longer than if the mutation is absent.
CONCLUSIONS
Evidence suggests atovaquone/proguanil treatment for P. falciparum malaria is effective. Late treatment failure is likely to be associated with a codon 268 mutation in cytochrome b, though recent evidence from animal models suggests these mutations may not spread within the population. However, early treatment failure is likely to arise through alternative mechanisms, requiring further investigation.
Topics: Atovaquone; Drug Combinations; Drug Resistance, Multiple; Drug Therapy, Combination; Electron Transport Complex III; Humans; Malaria, Falciparum; Malaria, Vivax; Mutation; Plasmodium falciparum; Proguanil; Travel; Treatment Failure
PubMed: 29237012
DOI: 10.1093/jac/dkx431 -
Veterinary Medicine and Science Jul 2021Cyclooxygenase (COX) isoforms-1 and -2 have been extensively investigated in cancer. Although COX-2 is the isoform most studied and has been described in several...
Cyclooxygenase (COX) isoforms-1 and -2 have been extensively investigated in cancer. Although COX-2 is the isoform most studied and has been described in several malignancies associated with histologic criteria of malignancy and worse prognosis, COX-1 has also been linked to some forms of cancer. With the present review our aim was to summarize the current state of knowledge and clarify if and in which type of tumours COX-1 and/or COX-2 expression have real prognostic implications. We searched PubMed database for prognostic studies using predefined inclusion criteria in order to ascertain the prognostic value of COX-1 and COX-2 in malignant neoplasia in dogs and cats. Eighteen studies were analysed. COX-2 was shown to be a negative prognostic factor in canine and feline mammary tumours, canine mast cell tumour, canine melanoma, canine osteosarcoma and canine renal cell carcinoma. COX-1 showed a negative prognostic value in feline oral squamous cell carcinoma (SCC). We found high heterogeneity among studies regarding COX immunohistochemical evaluation methodology even in the same type of neoplasia pointing out the need for its standardization at least by tumour type. The available data support the use of COX-2 as a prognostic factor in canine (mammary carcinoma, mast cell tumour, melanoma, osteosarcoma and renal carcinoma) and feline (mammary carcinoma) cancers. For COX-1, its use is advised in feline oral SCC.
Topics: Animals; Cat Diseases; Cats; Cyclooxygenase 1; Cyclooxygenase 2; Dog Diseases; Dogs; Gene Expression; Prognosis
PubMed: 33751829
DOI: 10.1002/vms3.460