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MedRxiv : the Preprint Server For... Oct 2023A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that...
Methylomic, proteomic, and metabolomic correlates of traffic-related air pollution: A systematic review, pathway analysis, and network analysis relating traffic-related air pollution to subclinical and clinical cardiorespiratory outcomes.
A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that could lead to cardiorespiratory disease. To provide a streamlined synthesis of what is known about the multiple mechanisms through which TRAP could lead cardiorespiratory pathology, we conducted a systematic review of the epidemiological literature relating TRAP exposure to methylomic, proteomic, and metabolomic biomarkers in adult populations. Using the 139 papers that met our inclusion criteria, we identified the omic biomarkers significantly associated with short- or long-term TRAP and used these biomarkers to conduct pathway and network analyses. We considered the evidence for TRAP-related associations with biological pathways involving lipid metabolism, cellular energy production, amino acid metabolism, inflammation and immunity, coagulation, endothelial function, and oxidative stress. Our analysis suggests that an integrated multi-omics approach may provide critical new insights into the ways TRAP could lead to adverse clinical outcomes. We advocate for efforts to build a more unified approach for characterizing the dynamic and complex biological processes linking TRAP exposure and subclinical and clinical disease, and highlight contemporary challenges and opportunities associated with such efforts.
PubMed: 37873294
DOI: 10.1101/2023.09.30.23296386 -
Mutation Research. Reviews in Mutation... 2022Epigenetic alterations, such as changes in DNA methylation, histones/chromatin structure, nucleosome positioning, and expression of non-coding RNAs, are recognized among... (Review)
Review
Epigenetic alterations, such as changes in DNA methylation, histones/chromatin structure, nucleosome positioning, and expression of non-coding RNAs, are recognized among key characteristics of carcinogens; they may occur independently or concomitantly with genotoxic effects. While data on genotoxicity are collected through standardized guideline tests, data collected on epigenetic effects is far less uniform. In 2016, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints to better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints. Since then, the number of studies of epigenetic effects of chemicals has nearly doubled. This review stands as an update on epigenetic alterations induced by occupational and environmental human carcinogens that were previously and recently classified as Group 1 by the International Agency for Research on Cancer. We found that the evidence of epigenetic effects remains uneven across agents. Studies of DNA methylation are most abundant, while reports concerning effects on non-coding RNA have increased over the past 5 years. By contrast, mechanistic toxicology studies of histone modifications and chromatin state alterations remain few. We found that most publications of epigenetic effects of carcinogens were studies in exposed humans or human cells. Studies in rodents represent the second most common species used for epigenetic studies in toxicology, in vivo exposures being the most predominant. Future studies should incorporate dose- and time-dependent study designs and also investigate the persistence of effects following cessation of exposure, considering the dynamic nature of most epigenetic alterations.
Topics: Carcinogens; Carcinogens, Environmental; Chromatin; DNA Damage; Epigenesis, Genetic; Epigenomics; Humans
PubMed: 35690411
DOI: 10.1016/j.mrrev.2021.108408 -
Medicine May 2020The incidence of triple negative breast cancer (TNBC) is at a relatively high level, and our study aimed to identify differentially expressed genes (DEGs) in TNBC and...
BACKGROUND
The incidence of triple negative breast cancer (TNBC) is at a relatively high level, and our study aimed to identify differentially expressed genes (DEGs) in TNBC and explore the key pathways and genes of TNBC.
METHODS
The gene expression profiling (GSE86945, GSE86946 and GSE102088) data were obtained from Gene Expression Omnibus Datasets, DEGs were identified by using R software, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools, and the protein-protein interaction (PPI) network of the DEGs was constructed by the STRING database and visualized by Cytoscape software. Finally, the survival value of hub DEGs in breast cancer patients were performed by the Kaplan-Meier plotter online tool.
RESULTS
A total of 2998 DEGs were identified between TNBC and health breast tissue, including 411 up-regulated DEGs and 2587 down-regulated DEGs. GO analysis results showed that down-regulated DEGs were enriched in gene expression (BP), extracellular exosome (CC), and nucleic acid binding, and up-regulated were enriched in chromatin assembly (BP), nucleosome (CC), and DNA binding (MF). KEGG pathway results showed that DEGs were mainly enriched in Pathways in cancer and Systemic lupus erythematosus and so on. Top 10 hub genes were picked out from PPI network by connective degree, and 7 of top 10 hub genes were significantly related with adverse overall survival in breast cancer patients (Pā<ā.05). Further analysis found that only EGFR had a significant association with the prognosis of triple-negative breast cancer (Pā<ā.05).
CONCLUSIONS
Our study showed that DEGs were enriched in pathways in cancer, top 10 DEGs belong to up-regulated DEGs, and 7 gene connected with poor prognosis in breast cancer, including HSP90AA1, SRC, HSPA8, ESR1, ACTB, PPP2CA, and RPL4. These can provide some guidance for our research on the diagnosis and prognosis of TNBC, and further research is needed to evaluate their value in the targeted therapy of TNBC.
Topics: Data Mining; Databases, Genetic; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Humans; Survival Analysis; Triple Negative Breast Neoplasms; Up-Regulation
PubMed: 32358373
DOI: 10.1097/MD.0000000000019986 -
Biomedicines Jan 2023Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated... (Review)
Review
Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated or dying neutrophils, decorated with various protein mediators, become solid-state reactors that can localize at the critical interface of blood with the intimal surface of diseased arteries alongside propagating and amplifying the regional injury. NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases. In response to disease-relevant stimuli, neutrophils undergo a specialized series of reactions that culminate in NET formation. DNA derived from either nuclei or mitochondria can contribute to NET formation. The DNA liberated from neutrophils forms a reticular mesh that resembles morphologically a net, rendering the acronym NETs particularly appropriate. The DNA backbone of NETs not only presents intrinsic neutrophil proteins (e.g., MPO (myeloperoxidase) and various proteinases) but can congregate other proteins found in blood (e.g., tissue factor procoagulant). This systematic review discusses the current hypothesis of neutrophil biology, focusing on the triggers and mechanisms of NET formation. Furthermore, the contribution of NETs to atherosclerosis and thrombosis is extensively addressed. Again, the use of NET markers in clinical trials was considered. Ultimately, given the vast body of the published literature, we aim to integrate the experimental evidence with the growing body of clinical information relating to NET critically.
PubMed: 36672621
DOI: 10.3390/biomedicines11010113 -
Ontario Health Technology Assessment... 2019Pregnant people have a risk of carrying a fetus affected by a chromosomal anomaly. Prenatal screening is offered to pregnant people to assess their risk. In recent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pregnant people have a risk of carrying a fetus affected by a chromosomal anomaly. Prenatal screening is offered to pregnant people to assess their risk. In recent years, noninvasive prenatal testing (NIPT) has been introduced clinically, which uses the presence of circulating cell-free fetal DNA in the maternal blood to quantify the risk of a chromosomal anomaly. At present, NIPT is publicly funded for pregnancies at high risk of a chromosomal anomaly, and available to pregnant people at average risk if they choose to pay out of pocket.
METHODS
We performed a systematic review of primary, empirical qualitative research that describes the experiences and perspectives of pregnant people, their families, clinicians, and others with lived experience relevant to NIPT. We were interested in the beliefs, experiences, preferences, and perspectives of these groups. We analyzed the evidence available in 36 qualitative and mixed-methods studies using the integrative technique of qualitative meta-synthesis.
RESULTS
Most people (pregnant people, clinicians, and others with relevant lived experience) said that NIPT offered important information to pregnant people and their partners. Most people were very enthusiastic about widening access to NIPT because it can provide information about chromosomal anomalies quite early in pregnancy, with relatively high accuracy, and without risk of procedure-related pregnancy loss. However, many groups cautioned that widening access to NIPT may result in routinization of this test, causing potential harm to pregnant people, their families, the health care system, people living with disabilities, and society as a whole. Widened logistical, financial, emotional, and informational access may be perceived as a benefit, but it can also confer harm on various groups. Many of these challenges echo historical critiques of other forms of prenatal testing, with some issues mitigated or exacerbated by the particular features of NIPT.
CONCLUSIONS
Noninvasive prenatal testing offers significant benefit for pregnant people but may also be associated with potential harms related to informed decision-making, inequitable use, social pressure to test, and reduced support for people with disabilities.
Topics: Female; Humans; Pregnancy; Attitude of Health Personnel; Patient Acceptance of Health Care; Patient Preference; Patient Satisfaction; Prenatal Diagnosis; Qualitative Research
PubMed: 30838086
DOI: No ID Found -
Frontiers in Immunology 2021The immune system is unique among all biological sub-systems in its usage of DNA-editing enzymes to introduce targeted gene mutations and double-strand DNA breaks to...
Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering.
The immune system is unique among all biological sub-systems in its usage of DNA-editing enzymes to introduce targeted gene mutations and double-strand DNA breaks to diversify antigen receptor genes and combat viral infections. These processes, initiated by specific DNA-editing enzymes, often result in mistargeted induction of genome lesions that initiate and drive cancers. Like other molecules involved in human health and disease, the DNA-editing enzymes of the immune system have been intensively studied in humans and mice, with little attention paid (< 1% of published studies) to the same enzymes in evolutionarily distant species. Here, we present a systematic review of the literature on the characterization of one such DNA-editing enzyme, activation-induced cytidine deaminase (AID), from an evolutionary comparative perspective. The central thesis of this review is that although the evolutionary comparative approach represents a minuscule fraction of published works on this and other DNA-editing enzymes, this approach has made significant impacts across the fields of structural biology, immunology, and cancer research. Using AID as an example, we highlight the value of the evolutionary comparative approach in discoveries already made, and in the context of emerging directions in immunology and protein engineering. We introduce the concept of 5-dimensional (5D) description of protein structures, a more nuanced view of a structure that is made possible by evolutionary comparative studies. In this higher dimensional view of a protein's structure, the classical 3-dimensional (3D) structure is integrated in the context of real-time conformations and evolutionary time shifts (4 dimension) and the relevance of these dynamics to its biological function (5 dimension).
Topics: Animals; Biological Evolution; Cytidine Deaminase; DNA; Humans; Protein Conformation; Protein Engineering
PubMed: 34135887
DOI: 10.3389/fimmu.2021.642343 -
Therapeutic Advances in Medical Oncology 2019Tissue evaluation for RAS (KRAS or NRAS) gene status in metastatic colorectal cancer (mCRC) patients represent the standard of care to establish the optimal therapeutic...
BACKGROUND
Tissue evaluation for RAS (KRAS or NRAS) gene status in metastatic colorectal cancer (mCRC) patients represent the standard of care to establish the optimal therapeutic strategy. Unfortunately, tissue biopsy is hampered by several critical limitations due to its invasiveness, difficulty to access to disease site, patient's compliance and, more recently, neoplastic tissue spatial and temporal heterogeneity.
METHODS
The authors performed a systematic literature review to identify available trials with paired matched tissue and ctDNA RAS gene status evaluation. The authors searched EMBASE, MEDLINE, Cochrane, www.ClinicalTrials.gov, and abstracts from international meetings. In total, 19 trials comparing standard tissue RAS mutational status matched paired ctDNA evaluated through polymerase chain reaction (PCR), next generation sequencing (NGS) or beads, emulsions, amplification and magnetics (BEAMing) were identified.
RESULTS
The pooled sensitivity and specificity of ctDNA were 0.83 (95% CI: 0.80-0.85) and 0.91 (95% CI: 0.89-0.93) respectively. The pooled positive predictive value (PPV) and negative predictive value (NPV) of the ctDNA were 0.87 (95% CI: 0.81-0.92) and 0.87 (95% CI: 0.82-0.92), respectively. Positive likelihood ratio (PLR) was 8.20 (95% CI: 5.16-13.02) and the negative likelihood ratio (NLR) was 0.22 (95% CI: 0.16-0.30). The pooled diagnostic odds ratio (DOR) was 50.86 (95% CI: 26.15-98.76), and the area under the curve (AUC) of the summary receiver operational characteristics (sROC) curve was 0.94.
CONCLUSION
The authors' meta-analysis produced a complete and updated overview of ctDNA diagnostic accuracy to test RAS mutation in mCRC. Results provide a strong rationale to include the RAS ctDNA test into randomized clinical trials to validate it prospectively.
PubMed: 31534493
DOI: 10.1177/1758835919874653 -
PloS One 2020Abdominal tuberculosis is a severe extrapulmonary tuberculosis, which can lead to serious complications. Early diagnosis and treatment are very important for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Abdominal tuberculosis is a severe extrapulmonary tuberculosis, which can lead to serious complications. Early diagnosis and treatment are very important for the prognosis and the diagnosis of abdominal tuberculosis is still difficult. This study aims to evaluate the diagnostic accuracy of nucleic acid amplification tests (NAATs) for abdominal tuberculosis using meta-analysis method.
METHODS
We will search PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, and the Wanfang database for studies evaluating the diagnostic accuracy of NAATs for abdominal tuberculosis until May 2020. We will include a systematic review and meta-analysis that evaluated the accuracy of NAATs for abdominal tuberculosis. Any types of study design with full text will be sought and included. The risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Stata version 15.0 with the midas command packages will be used to carry out meta-analyses.
RESULTS
The results will provide clinical evidence for diagnostic accuracy of NAATs for abdominal tuberculosis, and this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication.
CONCLUSION
This overview will provide evidence of NAATs for diagnosis of abdominal tuberculosis.
SYSTEMATIC REVIEW REGISTRATION
INPLASY202060030.
Topics: Abdomen; DNA, Bacterial; Databases, Factual; Humans; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Reference Standards; Tuberculosis
PubMed: 33315919
DOI: 10.1371/journal.pone.0243765 -
Frontiers in Physiology 2020Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting up to 15% of women at reproductive age. The main features of PCOS are hyperandrogenism...
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting up to 15% of women at reproductive age. The main features of PCOS are hyperandrogenism and irregular menstrual cycles together with metabolic dysfunctions including hyperinsulinemia and insulin resistance and a 4-fold increased risk of developing type 2 diabetes. Despite the high prevalence the pathophysiology of the syndrome is unclear. Insulin resistance in women with PCOS likely affect the skeletal muscle and recently it was demonstrated that changes in DNA methylation affects the gene expression in skeletal muscle that in part can explain their metabolic abnormalities. The objective of this work was to combine gene expression array data from different datasets to improve statistical power and thereby identify novel biomarkers that can be further explored. In this narrative review, we performed a meta-analysis of skeletal muscle arrays available from Gene Expression Omnibus and from publications. The eligibility criteria were published articles in English, and baseline (no treatment) skeletal muscle samples from women with PCOS and controls. The R package Metafor was used for integration of the datasets. One hundred and fourteen unique transcripts were differentially expressed in skeletal muscle from women with PCOS vs. controls ( < 0.05), 87% of these transcripts have not been previously identified as altered in PCOS muscle. , and had the largest differential increase in expression, and , and had the largest decrease in expression. Two genes, and were consistently upregulated ( < 0.05) in the individual analyses and meta-analysis. Based on the meta-analysis, we identified several dysregulated immunometabolic pathways as a part of the molecular mechanisms of insulin resistance in the skeletal muscle of women with PCOS. The transcriptomic data need to be verified by functional analyses as well as proteomics to advance our understanding of PCOS specific insulin resistance in skeletal muscle.
PubMed: 33192572
DOI: 10.3389/fphys.2020.573505 -
International Journal of Molecular... Apr 2024Molecular methods have become integral to microbiological research for microbial identification. This literature review focuses on the application of molecular methods... (Review)
Review
Molecular methods have become integral to microbiological research for microbial identification. This literature review focuses on the application of molecular methods in examining airborne bacteria and fungi in healthcare facilities. In January 2024, a comprehensive electronic search was carried out in esteemed databases including PubMed, Web of Science, and Scopus, employing carefully selected keywords such as ((bacteria) OR (virus) OR (fungi)) AND (aerosol) AND ((hospital) OR (healthcare) OR (dental office)) AND ((molecular) OR (PCR) OR (NGS) OR (RNA) OR (DNA) OR (metagenomic) OR (microarray)), following the PRISMA protocol. The review specifically targets healthcare environments with elevated concentrations of pathogenic bacteria. A total of 487 articles were initially identified, but only 13 met the inclusion criteria and were included in the review. The study disclosed that the prevalent molecular methodology for appraising aerosol quality encompassed the utilization of the PCR method, incorporating either 16S rRNA (bacteria) or 18S rRNA (fungi) amplification techniques. Notably, five diverse molecular techniques, specifically PFGE, DGGE, SBT, LAMP, and DNA hybridization methods, were implemented in five distinct studies. These molecular tests exhibited superior capabilities compared to traditional bacterial and fungal cultures, providing precise strain identification. Additionally, the molecular methods allowed the detection of gene sequences associated with antibiotic resistance. In conclusion, molecular testing offers significant advantages over classical microbiological culture, providing more comprehensive information.
Topics: Fungi; Aerosols; Bacteria; Air Microbiology; Humans; Health Facilities
PubMed: 38673740
DOI: 10.3390/ijms25084154