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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 -
European Review For Medical and... Sep 2021Non-Alcoholic Fatty Liver Disease (NAFLD), as a hepatic manifestation of metabolic syndrome (MET)-related obesity, insulin resistance, dyslipidemia, and hypertension, is...
OBJECTIVE
Non-Alcoholic Fatty Liver Disease (NAFLD), as a hepatic manifestation of metabolic syndrome (MET)-related obesity, insulin resistance, dyslipidemia, and hypertension, is the main cause of chronic liver disease. Inflammatory Bowel Diseases (IBD), (Crohn's Disease (CD) and Ulcerative Colitis (UC)), are often associated with extraintestinal manifestations. Of these, NAFLD is one of the most frequently reported. To highlight the etiopathogenesis of NAFLD in IBD, we performed a systematic review emphasizing the relationship between NAFLD genetic alterations, metabolic syndrome, and drugs.
MATERIALS AND METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed, Google Scholar, and Web of Science for literature updated from 2010 to 1 March 2021. Inclusion criteria for studies were observational design and Randomized Controlled Trials (RCTs); written in English; primary research only; based on adult patients, and human research only.
RESULTS
We identified nine studies on the link between NAFLD and IBD. Among these, two described the genetic predisposition to NAFLD of patients with IBD. Four reported an association between MetS and NAFLD in IBD patients. Regarding medications, none of four studies included, detected a relationship between NAFLD onset and IBD treatment (corticosteroids, immunomodulators, methotrexate, or biologics). However, a retrospective study showed a protective effect of anti-TNF alpha therapies against altered liver enzymes.
CONCLUSIONS
In this interplay between genetic, metabolic, drug, and inflammatory factors, the underlying pathogenic mechanisms behind NAFLD in IBD are still far from clear. Further studies are needed to better clarify the role of individual components influencing the development of NAFLD in IBD.
Topics: Acyltransferases; Autophagy-Related Proteins; Dyslipidemias; Female; GTP-Binding Proteins; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Hypertension; Inflammatory Bowel Diseases; Insulin Resistance; Male; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Phospholipases A2, Calcium-Independent
PubMed: 34604973
DOI: 10.26355/eurrev_202109_26800 -
Alzheimer's & Dementia : the Journal of... Nov 2018Inflammatory markers are often elevated in patients with dementia, including Alzheimer's disease (AD). However, it remains unclear whether inflammatory markers are... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Inflammatory markers are often elevated in patients with dementia, including Alzheimer's disease (AD). However, it remains unclear whether inflammatory markers are associated with the risk of developing dementia.
METHODS
We searched PubMed, Embase, and Cochrane library for prospective population-based studies reporting associations between inflammatory markers and all-cause dementia or AD. We used random effects meta-analyses to obtain pooled hazard ratios (HRs) and 95% confidence intervals of inflammatory markers (highest vs. lowest quantile) for all-cause dementia and AD.
RESULTS
Fifteen articles from 13 studies in six countries reported data that could be meta-analyzed. C-reactive protein (HR = 1.37 [1.05; 1.78]), interleukin-6 (HR = 1.40 [1.13; 1.73]), α1-antichymotrypsin (HR = 1.54 [1.14; 2.80]), lipoprotein-associated phospholipase A2 activity (HR = 1.40 [1.03; 1.90]), and fibrinogen were each associated with all-cause dementia, but neither was significantly associated with AD.
DISCUSSION
Several inflammatory markers are associated with an increased risk of all-cause dementia; however, these markers are not specific for AD. Whether inflammatory markers closely involved in AD pathology are associated with the risk of AD remains to be elucidated.
Topics: Dementia; Humans; Inflammation
PubMed: 29605221
DOI: 10.1016/j.jalz.2018.02.014 -
BMC Musculoskeletal Disorders Apr 2019This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory...
BACKGROUND
This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms?
METHODS
The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool.
RESULTS
In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95% CI, 1.1 to 10).
CONCLUSION
In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica.
Topics: Biomarkers; Cross-Sectional Studies; Humans; Inflammation Mediators; Observational Studies as Topic; Prospective Studies; Sciatica
PubMed: 30967132
DOI: 10.1186/s12891-019-2541-0 -
Medicina Clinica May 2023To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN).
PURPOSE
To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN).
PATIENTS AND METHODS
Patients diagnosed with MN were recruited after examining their renal biopsy in the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021. Among them, 24 patients with SR were included in this study and follow-up.
RESULTS
Twenty-four patients diagnosed with SR of PLA2R-associated MN were recruited; 11 were male, and 13 were female, with a mean age of 49.5±14.5 years (range, 30-77 years). The initial 24-hour urinary total protein and serum albumin levels were 0.29±0.14g/d and 37.5±4.4g/L, respectively, and the initial serum creatinine was 65.0±15.8μmol/L. During the follow-up of 33.9±19.1 months (range, 6-73 months), 22 (91.7%) patients maintained remission; however, one patient had impaired renal function due to acute coronary syndrome and coronary angiography findings, and one patient experienced a repeated relapse caused by respiratory tract infection, at 50 and 70 months. A systematic review of the relevant literature was conducted, and records of patients with SR of PLA2R-associated MN were retrieved from 16 case reports or case series with a total of 97 cases.
CONCLUSIONS
Most patients with SR of MN had a promising long-term prognosis, with only a few cases of relapse.
Topics: Humans; Male; Female; Adult; Middle Aged; Glomerulonephritis, Membranous; Remission, Spontaneous; Autoantibodies; Kidney; Prognosis
PubMed: 36690554
DOI: 10.1016/j.medcli.2022.10.014 -
IBRO Neuroscience Reports Jun 2021Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or...
Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or therapeutic modalities that can alleviate HIV-NP. Smoked cannabis has been reported to improve pain measures in patients with neuropathic pain. Cannabis, phytocannabinoids, and the endocannabinoids such N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), produce some of their effects via cannabinoid receptors (CBRs). Endocannabinoids are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase. We searched PubMed, Google Scholar, clinicaltrials.gov and clinicaltrialsregister.eu using various key words and their combinations for published papers that studied HIV-NP and cannabis, cannabinoids, or endocannabinoids up to 27th December 2020. All original research articles that evaluated the efficacy of molecules that modulate the endocannabinoid system (ECS) for the prevention and/or treatment of pain in HIV-NP animal models and patients with HIV-NP were included. The PubMed search produced a total of 117 articles, whereas the Google Scholar search produced a total of 9467 articles. Amongst the 13 articles that fulfilled the inclusion criteria 11 articles were found in both searches whereas 2 articles were found in Google Scholar only. The clinicaltrials.gov and clinicaltrialsregister.eu searches produced five registered trials of which three were completed and with results. Ten preclinical studies found that the endocannabinoids (2-AG and AEA), synthetic mixed CB1R/CB2R agonist WIN 55,212-2, a CB2R-selective phytocannabinoid β-caryophyllene, synthetic CB2R-selective agonists (AM1710, JWH015, JWH133 and Gp1a, but not HU308); FAAH inhibitors (palmitoylallylamide, URB597 and PF-3845) and a drug combination of indomethacin plus minocycline, which produces its effects in a CBR-dependent manner, either prevented the development of and/or attenuated established HIV-NP. Two clinical trials demonstrated greater efficacy of smoked cannabis over placebo in alleviating HIV-NP, whereas another clinical trial demonstrated that cannabidivarin, a cannabinoid that does not activate CBRs, did not reduce HIV-NP. The available preclinical results suggest that targeting the ECS for prevention and treatment of HIV-NP is a plausible therapeutic option. Clinical evidence shows that smoked cannabis alleviates HIV-NP. Further research is needed to find out if non-psychoactive drugs that target the ECS and are delivered by other routes than smoking could be useful as treatment options for HIV-NP.
PubMed: 34179865
DOI: 10.1016/j.ibneur.2021.01.004 -
Diabetes, Obesity & Metabolism Feb 2019The endocannabinoid system (ECS) is involved in many physiological processes including fertility, pain and energy regulation. The aim of this systematic review was to...
The endocannabinoid system (ECS) is involved in many physiological processes including fertility, pain and energy regulation. The aim of this systematic review was to examine the contribution of single nucleotide polymorphisms (SNPs) of the ECS to adiposity and glucose metabolism. Database searches identified 734 articles, of which 65 were included; these covered 70 SNPs in genes coding for cannabinoid receptors 1 and 2 (CB , CB ), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). No studies included SNPs relating to monoacylglycerol lipase or diacylglycerol lipase. The CB receptor SNP rs1049353 showed 17 associations with lower body mass index (BMI) and fat mass (five studies). It also showed three associations with lower insulin levels (one study). Conversely, the CB receptor SNP rs806368 was associated with increased BMI and waist circumference (two studies). The FAAH SNP rs324420 was associated with increased obesity (three studies). A haplotype of NAPE-PLD was associated with decreased BMI (one study). A total of 60 SNPs showed no association with any measured outcome. This review suggests a complex but important role of ECS SNPs in energy and glucose metabolism.
Topics: Adiposity; Amidohydrolases; Body Mass Index; Body Weight; Diabetes Mellitus; Endocannabinoids; Gene Frequency; Genetic Association Studies; Humans; Lipid Metabolism; Lipoprotein Lipase; Monoacylglycerol Lipases; Obesity; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptors, Cannabinoid; Signal Transduction
PubMed: 30129173
DOI: 10.1111/dom.13504 -
Current Cardiology Reviews Nov 2013Studies indicate that elevated plasma concentrations of lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with increased risk of cardiovascular disease.... (Review)
Review
Studies indicate that elevated plasma concentrations of lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with increased risk of cardiovascular disease. Lp-PLA2 seems to play a crucial role in the formation of plaques and acute inflammation, and plasma Lp-PLA2 could therefore potentially be used as a predictor of long-term outcome in ACS patients. To evaluate this, data concerning Lp-PLA2 as a predictor in ACS patients was gathered through a systematic literature review, and studies on this issue were extracted from relevant databases, incl. PubMed and Cochrane. A total of 14 articles were retrieved, but after thorough evaluation and elimination of irrelevant articles only seven studies were eligible for the literature review. All studies except two showed significant correlation between Lp-PLA2 and CV events in ACS patients. Only one study found an independent value to predict CV events 30 days after ACS. Altogether, there was inconsistency in the findings regarding the potential use of Lp-PLA2 and a lack of knowledge on several issues. Lp-PLA2 seems to give valuable information on which ACS patients are prone to new events and also provides important information on plaque size. However, more focused studies concerning genetic variations, time-window impact, patients with and without CV risk factors (e.g. diabetes), and treatment effects are needed. In conclusion, Lp-PLA2 offers new insight in the pathophysiological development of ACS, but until the aforementioned issues are addressed the biomarker will mainly be of interest in a research setting, not as a predictive parameter in a clinical setting.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Acute Coronary Syndrome; Biomarkers; Cardiovascular Diseases; Humans; Prognosis; Risk Factors
PubMed: 24313641
DOI: 10.2174/1573403x09666131202143349 -
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 -
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