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Mutation Research. Reviews in Mutation... 2016Airborne particles are small, solid particles projected into the air either by natural forces, or by mechanical or man-made processes, and include fibers and dusts.... (Review)
Review
Airborne particles are small, solid particles projected into the air either by natural forces, or by mechanical or man-made processes, and include fibers and dusts. Their toxicity is usually subsequent to inhalation and can lead to pulmonary dysfunctions and diseases, including cancer. Cytochalasin B blocked micronucleus assay in lymphocytes (L-CBMN) has been shown as a sensitive and reliable technique in assessing genotoxic exposure, An extensive search of the PubMed and Web of Science databases allowed retrieval of 18 articles on occupational or environmental exposure evaluating L-CBMN in subjects exposed to fibers or dusts (asbestos, silica, rockwool, beryllium, tobacco, and wood). For each study, mean L-CBMN levels were compared in exposed subjects vs. unexposed controls providing a point estimate, the Mean Ratio (MR). The high heterogeneity among retrieved studies and their relatively limited number did not allow a quantitative meta-analysis. However, the inter-quartile range of all MRs fell within the interval between 1.25 and 2.23, supporting the hypothesis that exposure to airborne particles increases DNA damage, although mechanisms of genotoxicity should be further investigated. A borderline significant correlation was found with SCE, but not with chromosome aberrations or comet assay. Future research should focus on exposure assessment, in order to perform proper dose-response studies and disentangle the effect of different compounds in mixed exposures. To fully exploit the cytome assay, L-CBMN frequency should be integrated with other endpoints, such as nucleoplasmic bridges and nuclear buds. The use of alternative tissues, such as nasal and buccal mucosa, and the implementation of other cytogenetic assay, may help to understand the effects of this exposure.
Topics: Asbestos; Biomarkers; Dust; Environmental Exposure; Humans; Micronucleus Tests
PubMed: 27894680
DOI: 10.1016/j.mrrev.2016.05.004 -
Ageing Research Reviews Sep 2023Telomere attrition is a proposed hallmark of aging. To evaluate the association of telomere length (TL) with chronological age across the human lifespan, we conducted a... (Meta-Analysis)
Meta-Analysis Review
Telomere attrition is a proposed hallmark of aging. To evaluate the association of telomere length (TL) with chronological age across the human lifespan, we conducted a systematic review and meta-analysis of 414 study samples comprising 743,019 individuals aged 0-112 years. We examined both cross-sectional and longitudinal data, and evaluated the impact of various biological and methodological factors including sex, health status, tissue types, DNA extraction procedures, and TL measurement methods. The pooled corrected correlation between TL and age from cross-sectional samples was -0.19 (95%CI: -0.22 to -0.15), which weakened with increased chronological age (β = 0.003, p < 0.001). Z-score change rates of TL across the lifespan showed a gradual decrease in shortening rate until around age 50 and remained at a relatively stable rate towards the elderly period. A greater attrition rate was observed in longitudinal than cross-sectional evaluations. For TL measured in base pairs, the median change rate of TL was -23 bp/year in cross-sectional samples and -38 bp/year in longitudinal samples. Methodological factors including TL measurement methods and tissue types impacted the TL-age correlation, while sex or disease status did not. This meta-analysis revealed the non-linear shortening trend of TL across the human lifespan and provides a reference value for future studies. Results also highlight the importance of methodological considerations when using TL as an aging biomarker.
Topics: Aged; Humans; Longevity; Cross-Sectional Studies; Telomere Shortening; Aging; Telomere
PubMed: 37567392
DOI: 10.1016/j.arr.2023.102031 -
PeerJ 2022This study aimed to assess the diagnostic performance of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC). (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to assess the diagnostic performance of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
We enrolled all relevant studies published up to 5 January 2022. Three primary subgroups were investigated: qualitative or quantitative ctDNA analyses, combined alpha-fetoprotein (AFP), and ctDNA assay. In addition to the three primary subgroups, we also evaluated the diagnostic value of methylated SEPTIN9 (mSEPT9), which has been studied extensively in the diagnosis of hepatocellular carcinoma. After a search based on four primary databases, we used a bivariate linear mixed model to analyze the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). We also plotted hierarchical summary receiver operating characteristics (HSROC) and utilized lambda as well as the area under the curve (AUC) to create summary receiver operating characteristic (SROC) curves to estimate the diagnostic value of ctDNA.
RESULTS
A total of 59 qualified articles with 9,766 subjects were incorporated into our meta-analysis. The integrated SEN, SPE, and DOR in the qualitative studies were 0.50 (95% CI [0.43-0.56]), 0.90 (95% CI [0.86-0.93]), and 8.72 (95% CI [6.18-12.32]), respectively, yielding an AUC of 0.78 and lambda of 1.93 (95% CI [1.56-2.33]). For quantitative studies, the corresponding values were 0.69 (95% CI [0.63-0.74]), 0.84 (95% CI [0.77-0.89]), 11.88 (95% CI [7.78-18.12]), 0.81, and 2.32 (95% CI [1.96-2.69]), respectively. Six studies were included to evaluate the SETP9 methylation, which yielded an AUC of 0.86, a SEN of 0.80 (95% CI [0.71-0.87]), and a SPE of 0.77 (95% CI [0.68-0.85]). Likewise, ctDNA concentration yielded an AUC of 0.73, with a SEN of 0.63 (95% CI [0.56-0.70]) and a SPE of 0.86 (95% CI [0.74-0.93]). AFP combined with ctDNA assay resulted in an AUC of 0.89, with a SEN of 0.82 (95% CI [0.77-0.86]) and a SPE of 0.84 (95% CI [0.76-0.90]).
CONCLUSION
This study shows that circulating tumor DNA, particularly mSEPT9, shows promising diagnostic potential in HCC; however, it is not enough to diagnose HCC independently, and ctDNA combined with conventional assays such as AFP can effectively improve diagnostic performance.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Circulating Tumor DNA; ROC Curve
PubMed: 36348665
DOI: 10.7717/peerj.14303 -
Cancer Investigation Jul 2023This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of... (Meta-Analysis)
Meta-Analysis Review
This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non-small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research.
Topics: Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Mutation; Biomarkers, Tumor; Circulating Tumor DNA
PubMed: 37272675
DOI: 10.1080/07357907.2023.2220820 -
Journal of Translational Medicine Oct 2023Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.
METHODS
We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).
RESULTS
Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen's d test) compared to both healthy and diseased controls.
CONCLUSION
This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.
Topics: Humans; Encephalitis; Fatigue Syndrome, Chronic; Fibromyalgia; Virus Diseases
PubMed: 37898798
DOI: 10.1186/s12967-023-04635-0 -
Cancer Research Jun 2004Cancers of the anogenital tract as well as some head and neck cancers are caused by persistent infections with high-risk type human papillomaviruses (HPVs). Two viral... (Review)
Review
Cancers of the anogenital tract as well as some head and neck cancers are caused by persistent infections with high-risk type human papillomaviruses (HPVs). Two viral oncogenes, E6 and E7, induce severe chromosomal instability associated with centrosome aberrations, anaphase bridges, chromosome lagging, and breaking. This occurs early in preneoplastic lesions, when the viral genome still persists in an episomal state. In most invasive cancers and also in a few high-grade dysplastic lesions, however, integration of high-risk HPV genomes into the host genome is observed. Integration seems to be a direct consequence of chromosomal instability and an important molecular event in the progression of preneoplastic lesions. Disruption or deregulation of defined critical cellular gene functions by insertional mutagenesis by integrated HPV genome fragments has been hypothesized as one major promoting factor in the pathogenesis of HPV-associated cancers. This hypothesis was based on the detection of HPV integration events in the area of tumor-relevant genes in few cases. Here, we reviewed >190 reported integration loci with respect to changes in the viral structure and the targeted genomic locus. This analysis confirms that HPV integration sites are randomly distributed over the whole genome with a clear predilection for genomic fragile sites. No evidence for targeted disruption or functional alteration of critical cellular genes by the integrated viral sequences could be found.
Topics: Cell Transformation, Viral; DNA, Viral; Epithelial Cells; Female; Gene Expression Regulation, Viral; Genital Neoplasms, Female; Humans; In Situ Hybridization, Fluorescence; Papillomaviridae; Uterine Cervical Neoplasms; Vaginal Neoplasms; Virus Integration; Vulvar Neoplasms; Uterine Cervical Dysplasia
PubMed: 15172997
DOI: 10.1158/0008-5472.CAN-04-0009 -
European Journal of Neurology Nov 2023The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous.... (Review)
Review
BACKGROUND AND PURPOSE
The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous. These discrepancies arise not only from the highly heterogeneous pathology of PD, but also from widely varying methodologies at all stages of the workflow, from sampling to final statistical analysis. The aim of the present work is to harmonize the workflow across studies to reduce the methodological heterogeneity and to perform a pooled analysis to account for other sources of heterogeneity.
METHODS
We performed a systematic review to identify studies comparing the gut microbiota of PD patients to healthy controls. A workflow was designed to harmonize processing across all studies from bioinformatics processing to final statistical analysis using a Bayesian random-effects meta-analysis based on individual patient-level data.
RESULTS
The results show that harmonizing workflows minimizes differences between statistical methods and reveals only a small set of taxa being associated with the pathogenesis of PD. Increased shares of the genera Akkermansia and Bifidobacterium and decreased shares of the genera Roseburia and Faecalibacterium were most characteristic for PD-associated microbiota.
CONCLUSIONS
Our study summarizes evidence that reduced levels of butyrate-producing taxa in combination with possible degradation of the mucus layer by Akkermansia may promote intestinal inflammation and reduced permeability of the gut mucosal layer. This may allow potentially pathogenic metabolites to transit and enter the enteric nervous system.
PubMed: 36593694
DOI: 10.1111/ene.15671 -
Mycoplasma pneumoniae infection and risk of childhood asthma: A systematic review and meta-analysis.Microbial Pathogenesis Jun 2021The etiology of childhood asthma is multifactorial, atypical bacterial pathogens, including Mycoplasma pneumoniae, have been proposed as possible risk factors or... (Meta-Analysis)
Meta-Analysis Review
The etiology of childhood asthma is multifactorial, atypical bacterial pathogens, including Mycoplasma pneumoniae, have been proposed as possible risk factors or contributors. This review aims to assess the possible association between M. pneumoniae infection and childhood asthma. We searched major international literature databases (up to January 10, 2021) to identify relevant studies. We used a random-effects meta-analysis (REM) model to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Several subgroups analyses were performed concerning the IgG, IgM, and DNA detection of M. pneumoniae infection. We included 22 eligible studies; these studies involved a total of 5064 children. We found that there was a statistically significant association between M. pneumoniae infection, as determined by IgM serology (OR, 3.13; 95% CI, 1.78-5.48), and DNA detection (OR, 1.57; 95% CI, 1.25-1.97) with increased risk of any type of childhood asthma. Moreover, children with acute asthma had significantly higher seropositivity for anti- M. pneumoniae IgM antibodies (OR, 4.43; 95% CI, 2.80-7.02) than children with stable asthma. Although our findings indicate a positive association between M. pneumoniae infection and childhood asthma, well-designed and -controlled studies are need in the future to rigorously test this association and identify the underlying mechanisms.
Topics: Asthma; Child; Humans; Immunoglobulin M; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Risk Factors
PubMed: 33932544
DOI: 10.1016/j.micpath.2021.104893 -
Journal of Receptor and Signal... Apr 2017Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption,... (Review)
Review
CONTEXT
Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption, particularly in the skin, eyes and lungs, systemic spread of the agent also has detrimental effects on gonads, bone marrow and nervous system. Moreover, chronic exposure of SM to respiratory system causes death. Inducing oxidative stress, and disturbing DNA and tissue repair systems, inflammation and cell death signaling pathways have been introduced as molecular mechanisms of the injury.
METHODS
In this systematic review, more than 1200 (2000-2014) articles focusing on gross or molecular pathological reports in the acute phase of the respiratory injury after SM exposure were reviewed, followed by two different layers of gross and molecular pathological data (clinic and laboratory) integrated together in a spatio-temporal order. Role of epithelial, neutrophil and macrophage cells and three signaling pathways of inflammation, oxidative stress and cell death are covered in details.
RESULTS AND CONCLUSION
Our results propose a critical role of interleukin-17 producing cells in acute and chronic inflammatory responses.
Topics: Cell Death; Chemical Warfare Agents; DNA Damage; DNA Repair; Inflammation; Interleukin-17; Mustard Gas; Oxidative Stress; Signal Transduction
PubMed: 27485024
DOI: 10.1080/10799893.2016.1212374 -
European Journal of Cancer Care Jan 2014The aim of this systematic review and meta-analysis was to investigate the effectiveness of exercise for colorectal cancer patients. PubMed/Medline, Scopus and the... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review and meta-analysis was to investigate the effectiveness of exercise for colorectal cancer patients. PubMed/Medline, Scopus and the Cochrane Library were searched through December 2012 without language restrictions. Randomised controlled trials (RCTs) comparing exercise interventions to control conditions were analysed when they assessed health-related quality of life, fatigue, physical fitness, survival and/or tumour-associated biomarkers in colorectal cancer patients. Risk of bias was assessed using the risk of bias tool recommended by the Cochrane Back Review Group. Literature search identified 342 non-duplicate records of which five RCTs with a total of 238 patients were included; three RCTs had low risk of bias. No evidence was found for short-term effects on quality of life [standardised mean difference (SMD) = 0.18; 95% confidence interval (CI) -0.39, 0.76; P = 0.53] or fatigue (SMD = 0.18; 95% CI -0.22, 0.59; P = 0.38). There was strong evidence for short-term improvements of physical fitness after aerobic exercise compared with controls (SMD = 0.59; 95% CI 0.25, 0.93; P < 0.01). One RCT each assessed immune parameters and oxidative DNA damage. No study reported survival rates or safety data. Given this insufficient evidence and the lack of safety data, no recommendation can be made regarding exercise interventions as a routine intervention for colorectal cancer patients.
Topics: Colorectal Neoplasms; Exercise Therapy; Fatigue; Humans; Physical Fitness; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 23834462
DOI: 10.1111/ecc.12093