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Frontiers in Immunology 2020There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological...
There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological research and in the assessment of the neutralizing efficacy of snake antivenoms. This is a challenging task owing to the inherent complexity of snake venoms. The state of the art on this topic is hereby reviewed, with emphasis on the studies in which a correlation has been observed between toxicity tests and surrogate assays, particularly in the study of lethal activity of venoms and its neutralization. Correlations have been described with some venoms-antivenoms when using: (a) enzyme immunoassays, (b) hemagglutination, (c) enzyme assays (proteinase, phospholipase A), (d) coagulant effect on plasma, (e) cell culture assays for cytotoxicity, (f) functional assays for assessing neurotoxicity , (g) use of hens' eggs, and (h) antivenomics. Additionally, the routine introduction of analgesia in these assays and the design of more 'humane' protocols for the lethality test are being pursued. It is expected that the next years will witness a growing awareness of the relevance of the 3Rs principles in antivenom testing, and that new alternatives and more 'humane' experimental designs will emerge in this field.
Topics: Animals; Antivenins; Humans; In Vitro Techniques; Neutralization Tests; Snake Venoms
PubMed: 33505403
DOI: 10.3389/fimmu.2020.617429 -
Microbial Pathogenesis Dec 2020Candida albicans is the main causative agent of oral lesions in HIV-infected patients and its oral colonization is a potential source of systemic dissemination. Although... (Meta-Analysis)
Meta-Analysis Review
Candida albicans is the main causative agent of oral lesions in HIV-infected patients and its oral colonization is a potential source of systemic dissemination. Although the high prevalence of lesions in HIV patients can be explained by the immunosuppressive condition, several studies have reported that natural selection can make C. albicans more virulent in this group of patients. Comparisons of the activity of exoenzymes (phospholipase, proteinase and hemolysin) in C. albicans isolated from HIV-infected and uninfected patients have yielded conflicting results. This study aimed, through a systematic review and meta-analysis, to answer the question: "Is the hydrolytic enzymatic activity of C. albicans, isolated from the oral cavity, different in individuals infected and not infected with HIV?" The question was addressed using the PECO framework: P (Population): children and adults, E (Exposure): HIV infection, C (Comparator): non-HIV-infected patients; O (Outcomes): exoenzymes activity i.e. phospholipase, proteinase and hemolysin. We conducted a systematic search on Pubmed, Embase, Scopus, Livivo, Lilacs, Web of Science, and Science Direct databases, and Google Scholar. The MAStARI tool was used to evaluate the risk of bias in the selected studies. From 2259 studies, 19 were included in this review and 11 comprised the meta-analysis. The activity of phospholipase (M-H = 0.15; Z = 2,76; p = 0.0006) and hemolysin exoenzymes (M-H = 0.07; z = 1,94; p = 0.05) was higher in C. albicans isolated from the oral cavity of HIV-infected patients, whereas the levels of protease activity were not different compared with non-HIV-infected individuals. This study showed a higher phospholipase and hemolysin activity in C. albicans isolates from the oral cavity of HIV-infected patients.
Topics: Adult; Candida albicans; Candidiasis, Oral; Child; HIV Infections; Humans; Phospholipases
PubMed: 32920148
DOI: 10.1016/j.micpath.2020.104477 -
Molecular Biology Reports Oct 2020Bipolar disorder (BD) is a mood psychiatric disorder described by changes between depressive, hypomanic, or manic episodes. The aimed of the present study was evaluated...
Bipolar disorder (BD) is a mood psychiatric disorder described by changes between depressive, hypomanic, or manic episodes. The aimed of the present study was evaluated possible changes in the AA pathway in BD through a systematic review of observational studies. A search in the electronic databases was proceeded, on Cochrane Library, MEDLINE, EMBASE, PsycINFO, Google Scholar and the British Library for studies published until August 2020. A search strategy was developed using the terms: "Bipolar Disorder" and "Phospholipase A2" or "Arachidonic Acids" or "Cyclooxygenase 2" or "Prostaglandins E" as text words and Medical Subject Headings (i.e., MeSH and EMTREE). Seven primary studies were included in the systematic review, with a total of 246 BD patients, 20 depression patients, and 425 heathy controls (HC). The studies showed contradictory results in the AA and PLA2, no primary articles with COX and PGE2 assessments were included in this review. According to the Newcastle-Ottawa quality score scale (NOS), our systematic review presented high quality. The investigation of the inflammatory pathway of AA still needs further investigation and evidence, given the growing number of studies suggesting the efficacy of anti-inflammatory drugs as adjunctive therapy in the pharmacological treatment of BD.
Topics: Anti-Inflammatory Agents; Arachidonic Acids; Bipolar Disorder; Humans; Inflammation; Signal Transduction
PubMed: 32880834
DOI: 10.1007/s11033-020-05785-w -
Neuropsychiatric Disease and Treatment 2020The phospholipase A2 Group 6 (, also known as , and ) gene encodes a group VIA calcium-independent phospholipase A2. Genetic polymorphism of has been indicated to be...
BACKGROUND
The phospholipase A2 Group 6 (, also known as , and ) gene encodes a group VIA calcium-independent phospholipase A2. Genetic polymorphism of has been indicated to be involved in conferring susceptibility for Parkinson's disease (PD), whereas conclusive results have not been obtained. Thus, we intended to conduct a systematic review to determine if genetic variation confers a greater susceptibility to PD.
METHODS
All case-control studies that investigated the association of the polymorphisms with the risk of PD published before 15 July 2018 were included. The literature was comprehensively searched and identified in five English databases (EBSCO, Pubmed, OVID, EMBASE and ISI Web of Knowledge) and four Chinese databases (Wanfang database, Chinese Biomedical Literature Database, China Academic Journals Database and VIP database). We performed analyses of study characteristics, heterogeneity, and forest plot in analyses analogous to dominant, codominant and additive models with the pooled odds ratio (OR) in fixed- or random-effects models as the measure of association.
RESULTS
A total of 664 potentially relevant studies were retrieved with the initial search, of which eight studies fulfilled the inclusion criteria, and included 2,779 PD patients and 3,291 control participants,. Among all the reported 27 genetic variants, 15 single nucleotide polymorphisms (SNPs) were present only in patients, and only five available SNPs (rs2267369, rs140758033, c.1959T>A (Gly653Gly), rs76718524, rs199935023) were pooled in the meta-analysis. However, there was no evidence for a significant association between the five SNPs and PD risk in dominant, codominant and allele models, suggesting a lack of association between genetic variation and PD susceptibility.
CONCLUSION
The present study assessed the association of genetic polymorphism with the risk PD, and the result strongly demonstrates that polymorphism is not associated with PD susceptibility.
PubMed: 32801710
DOI: 10.2147/NDT.S254065 -
Hepatology Communications Jul 2020Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from...
Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from studies comparing lean with obese NAFLD or with healthy subjects on prevalence, comorbidities, liver chemistry and histology, and metabolic/inflammatory markers were analyzed. Data were reported as odds ratio and 95% confidence interval for categorical variables and difference of means for continuous variables. Analysis of 53 studies on 65,029 subjects with NAFLD (38,084 lean) and 249,544 healthy subjects showed a prevalence of lean NAFLD at 11.2% in the general population. Among individuals with NAFLD, the prevalence of lean NAFLD was 25.3%. Lean NAFLD versus healthy subjects had higher odds for abnormalities on metabolic profile, including metabolic syndrome and its components, renal and liver function, and patatin-like phospholipase domain-containing protein 3 () G allele; and inflammatory profile, including uric acid and C-reactive protein. The abnormalities were less severe among lean versus obese NAFLD on metabolic syndrome with its components, renal and liver chemistry, liver stiffness measurement, and transmembrane 6 superfamily member 2 polymorphisms, and uric acid levels as markers of inflammation. Lean NAFLD had less severe histologic findings, including hepatocyte ballooning, lobular inflammation, NAFLD activity score, and fibrosis stage. Limited data also showed worse outcomes between obese versus lean NAFLD. Lean NAFLD is a distinct entity with metabolic, biochemical, and inflammatory abnormalities compared to healthy subjects and a more favorable profile, including liver histology of steatohepatitis and fibrosis stage, compared to obese NAFLD. We suggest that prospective multicenter studies examine long-term hepatic and extrahepatic outcomes in individuals with lean NAFLD.
PubMed: 32626829
DOI: 10.1002/hep4.1519 -
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 -
Gene Jun 2020The association between rs738409 (C>G, I148M) with patatin-like phospholipase domain-containing 3 (PNPLA3) gene and the risk of hepatocellular carcinoma (HCC) was... (Meta-Analysis)
Meta-Analysis
PNPLA3 rs738409 is not associated with the risk of hepatocellular carcinoma and persistent infection of hepatitis B virus (HBV) in HBV-related subjects: A case-control study and meta-analysis on Asians.
The association between rs738409 (C>G, I148M) with patatin-like phospholipase domain-containing 3 (PNPLA3) gene and the risk of hepatocellular carcinoma (HCC) was controversial in different ethnic populations. Our study aimed to explore the effect of PNPLA3 rs738409 on the risk of HCC and persistent infection of Hepatitis B virus (HBV) in a Chinese HBV-related population, and further evaluate its role in HCC risk among Asians. First, we performed a case-control study by recruiting 786 HBV-related HCC cases, 695 HBV persistent carriers and 719 HBV natural clearance subjects. PNPLA3 rs738409 was genotyped by MassARRAY platform. Second, we conducted a systematic review and meta-analysis on Asians to further validate our results. Our case-control study demonstrated that PNPLA3 rs738409 was not associated with HCC risk or persistent HBV infection (All P > 0.05). The subsequent meta-analysis included 13 Asian studies with 9,802 subjects. Results showed that PNPLA3 rs738409 might increase HCC risk among healthy subjects (pooled odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.11-1.95), but it had no influence on the development of HCC among HBV-related subjects (pooled OR = 1.07, 95%CI = 0.89-1.30). Our case-control study highlights that PNPLA3 rs738409 is probably not associated with the risk of HCC or persistent HBV infection in a Chinese HBV-related population. Besides, our systematic review and meta-analysis on Asians further suggest that PNPLA3 rs738409 may confer an increased risk of HCC among healthy people, but contribute little to the development of HCC among HBV-related subjects. Future studies are required to confirm these results.
Topics: Adult; Aged; Asian People; Carcinoma, Hepatocellular; Case-Control Studies; Female; Genetic Predisposition to Disease; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lipase; Liver Neoplasms; Male; Membrane Proteins; Middle Aged; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors
PubMed: 32173542
DOI: 10.1016/j.gene.2020.144585 -
Pediatric Obesity Jun 2020The effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of paediatric and adolescent nonalcoholic... (Meta-Analysis)
Meta-Analysis
Effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta-analysis of paediatric and adolescent individuals.
BACKGROUND
The effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of paediatric and adolescent nonalcoholic fatty liver disease (NAFLD) remains inconclusive.
OBJECTIVES
We aimed to estimate the effect of this polymorphism not only on early-onset NAFLD risk and severity but also on metabolic syndromes susceptibility.
METHODS
A systematic literature search was performed to identify relevant datasets. The odds ratio of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals were calculated to assess the strength of the associations.
RESULTS
Twenty-seven studies comprising 10 070 subjects were eligible. The summary effect showed that this polymorphism increased susceptibility to NAFLD development. Furthermore, it also indicated that nonalcoholic steatohepatitis (NASH) was more frequently observed in G allele carriers among paediatric and adolescent NAFLD patients. Moreover, the meta-analysis suggested that the variant was significantly associated with elevated liver damage indexes, including serum alanine transaminase, aspartate transaminase, gamma-glutamyltransferase concentrations, and liver fat content. However, the summary estimates for insulin resistance, lipid metabolism, and adiposity showed no significant associations.
CONCLUSIONS
The PNPLA3 I148M polymorphism is associated with elevated early-onset NAFLD risk, severity, and liver damage but not with related metabolic syndromes.
Topics: Adolescent; Child; Female; Genetic Predisposition to Disease; Humans; Lipase; Male; Membrane Proteins; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Polymorphism, Genetic; Risk
PubMed: 32020770
DOI: 10.1111/ijpo.12615 -
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 -
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