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Social Science & Medicine (1982) Mar 2021We systematically review the literature on social epigenetics, examining how empirical research to date has conceptualized and operationalized social determinants of... (Review)
Review
OBJECTIVE
We systematically review the literature on social epigenetics, examining how empirical research to date has conceptualized and operationalized social determinants of health (SDOH).
METHODS
Using comprehensive search procedures, we identified studies that consider the impact of SDOH on DNA methylation (DNAm), the most common measure of epigenetic change in research on human adult populations. We analyzed the studies to determine: 1) which populations and environments have been investigated in the literature; 2) how SDOH are defined and operationalized; 3) which SDOH have been linked to DNAm; and 4) what lessons from the SDOH literature can be better integrated into future studies exploring the social determinants of health and epigenetic outcomes.
RESULTS
We identified 67 studies, with 39 to 8397 participants. The SDOH most commonly considered were early life socioeconomic exposures and early life trauma or mental health. Our review highlights four broad challenges: a) high dependence on convenience sampling, b) limited racial/ethnic, and geographic diversity in sampling frames, c) overreliance on individual sociodemographic characteristics as proxies for broader stratification processes, and d) a focus on downstream social determinants of health and individualized experiences with social stressors.
CONCLUSIONS
Future social epigenetics research should prioritize larger, more diverse and representative population-based samples and employ the SDOH framework to better inform the conceptualization of research questions and interpretation of findings. In particular, the simplified depiction of race/ethnicity, gender, and socioeconomic status as individual-level characteristics should be updated with an explicit acknowledgement that these characteristics are more accurately interpreted as cues used by society to differentiate subpopulations. Social epigenetics research can then more clearly elucidate the biological consequences of these social exposures for patterns of gene expression, subsequent disease etiology, and health inequities.
Topics: Adult; Epigenesis, Genetic; Humans; Social Determinants of Health
PubMed: 33610974
DOI: 10.1016/j.socscimed.2021.113738 -
Frontiers in Neuroendocrinology Apr 2022Adverse childhood experiences (ACEs) may leave long-lasting neurobiological scars, increasing the risk of developing mental disorders in later life. However, no review... (Review)
Review
Adverse childhood experiences (ACEs) may leave long-lasting neurobiological scars, increasing the risk of developing mental disorders in later life. However, no review has comprehensively integrated existing evidence across the fields: hypothalamic-pituitary-adrenal axis, immune/inflammatory system, neuroimaging, and genetics/epigenetics. We thus systematically reviewed previous meta-analyses towards an integrative account of ACE-related neurobiological alterations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a total of 27 meta-analyses until October 2021 were identified. This review found that individuals with ACEs possess blunted cortisol response to psychosocial stressors, low-grade inflammation evinced by increased C-reactive protein levels, exaggerated amygdalar response to emotionally negative information, and diminished hippocampal gray matter volume. Importantly, these alterations were consistently observed in those with and without psychiatric diagnosis. These findings were integrated and discussed in a schematic model of ACE-related neurobiological alterations. Future longitudinal research based on multidisciplinary approach is imperative for ACE-related mental disorders' prevention and treatment.
Topics: Adverse Childhood Experiences; Humans; Hypothalamo-Hypophyseal System; Mental Disorders; Pituitary-Adrenal System; Stress, Psychological
PubMed: 35331780
DOI: 10.1016/j.yfrne.2022.100994 -
Scientific Reports Oct 2022The association between the expression of Lysyl oxidase (LOX) and its clinicopathological parameters and prognosis in patients with gastric cancer (GC) is still... (Meta-Analysis)
Meta-Analysis
The association between the expression of Lysyl oxidase (LOX) and its clinicopathological parameters and prognosis in patients with gastric cancer (GC) is still disputed. We performed this meta-analysis and bioinformatics analysis to clarify the relationship between the expression and methylation level of LOX with its clinicopathological parameters and prognostic value. We applied odds ratios with a 95% confidence interval to study the associations between LOX expression and clinicopathological parameters and overall survival (OS) in GC patients. In addition, association analysis of promoter methylation levels and expression of LOX with its prognostic value was performed using the Cancer Genome Atlas (TCGA) and four Gene Expression Omnibus (GEO) datasets. The PRISMA 2020 checklist was used to guide the data extraction and analysis. This meta-analysis includes seven clinical studies with a total of 1435 GC patients. LOX expression was related to lymph node metastasis and tumor distant metastasis in GC patients, but not to gender, tumor differentiation, Lauren classification, or tumor depth of invasion. Patients with GC grouped in high-expression of LOX had a much worse OS than those in low-expression. In addition, TCGA and four GEO datasets with 1279 samples were included in the bioinformatics analysis. The bioinformatics analysis showed that patients with high LOX levels had poor OS; low levels of methylation at some cg sites in the LOX gene were strongly related to poor OS and PFS; and methylation levels of LOX are negatively correlated with advanced tumor stage. The conclusion from comprehensive DNA methylation and gene expression analysis supports LOX as a specific diagnostic and prognosis biomarker in GC. LOX expression was related to lymph node metastasis, tumor distant metastasis and poor prognosis in GC. Low methylation levels were related to advanced tumor stage and poor prognosis in GC. Integrative analysis supports LOX as a specific diagnostic and prognosis biomarker in GC.
Topics: Biomarkers; Biomarkers, Tumor; Computational Biology; Humans; Lymphatic Metastasis; Prognosis; Protein-Lysine 6-Oxidase; Stomach Neoplasms
PubMed: 36202905
DOI: 10.1038/s41598-022-21402-1 -
Evidence-based Complementary and... 2015Objective. To evaluate the efficacy and safety of Kushenin (KS) combined with nucleoside analogues (NAs) for chronic hepatitis B (CHB). Methods. Randomized controlled... (Review)
Review
Objective. To evaluate the efficacy and safety of Kushenin (KS) combined with nucleoside analogues (NAs) for chronic hepatitis B (CHB). Methods. Randomized controlled trials (RCTs) of KS combined with NAs for CHB were identified through 7 databases. Frequencies of loss of serum HBeAg, HBeAg seroconversion, undetectable serum HBV-DNA, ALT normalization, and adverse events at 48 weeks were abstracted by two reviewers. The Cochrane software was performed to assess the risk of bias in the included trials. Data were analyzed with Review Manager 5.3 software. Results. 18 RCTs involving 1684 subjects with CHB were included in the analysis. KS combined with NAs including lamivudine (LAM), entecavir (ETV), adefovir dipivoxil (ADV), and telbivudine (TLV) showed different degree of improvement in CHB indices. KS combined with NAs increased the frequency of loss of serum HBeAg, HBeAg seroconversion, undetectable HBV-DNA levels, and ALT normalization compared with single agents. It also decreased serum ALT and AST level after one-year treatment. However, KS combined with TLV did not show a significant difference in CHB indices. The side-effects of KS combined with NAs were light and of low frequency. Conclusion. KS combined with NAs improves the efficacy of NAs in CHB.
PubMed: 26347789
DOI: 10.1155/2015/529636 -
Complex Psychiatry 2023Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and... (Review)
Review
INTRODUCTION
Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals.
METHODS
A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms.
RESULTS
Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species.
DISCUSSION
Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.
PubMed: 37404872
DOI: 10.1159/000529536 -
BMC Medicine Mar 2016Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions... (Review)
Review
BACKGROUND
Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods.
METHODS
We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses.
RESULTS
Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data.
CONCLUSIONS
As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission.
Topics: Bacterial Typing Techniques; Genetic Variation; Genome, Bacterial; Genome-Wide Association Study; Humans; Mycobacterium tuberculosis; Recurrence; Sequence Analysis, DNA; Tuberculosis
PubMed: 27005433
DOI: 10.1186/s12916-016-0566-x -
Antioxidants (Basel, Switzerland) Dec 2021Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is... (Review)
Review
Physical activity may benefit health by modulating oxidative stress and inflammation. However, the selection of suitable exercise-induced oxidative stress biomarkers is still challenging. This study aimed at systematically summarizing the available evidence on exercise-induced oxidative stress measured in urine and/or saliva. Two meta-analyses including the most frequently quantified biomarkers of oxidative stress, namely, urinary isoprostane and DNA oxidation products, were performed. Three electronic databases (PubMed, EMBASE and Cochrane CENTRAL) were interrogated. Among 4479 records, 43 original articles were included in the systematic review and 11 articles were included in meta-analysis I and II, respectively. We observed a pooled trend of increase of urinary isoprostanes in response to physical activity (+0.95, 95% CI: -0.18; 2.09). In comparison with aerobic exercise, anaerobic training determined a greater induction of isoprostanes (+5.21, 95% CI: 2.76; 7.66, < 0.0001), which were markedly increased after vigorous physical activity (+6.01, 95% CI: 1.18; 10.84, < 0.001) and slightly decreased in response to exercise interventions protracted over time (e.g., months) (-1.19, 95% CI: -2.25; -0.12, < 0.001). We recommend the most integrative approach of oxidative stress multi-marker panels in response to physical activity instead of selecting one preferential biomarker to quantify physical activity-induced oxidative stress in humans.
PubMed: 34943111
DOI: 10.3390/antiox10122008 -
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 -
Cells Mar 2023Epigenetic research has the potential to improve our understanding of the pathogenesis of cancer, specifically non-small-cell lung cancer, and support our efforts to... (Review)
Review
Epigenetic research has the potential to improve our understanding of the pathogenesis of cancer, specifically non-small-cell lung cancer, and support our efforts to personalize the management of the disease. Epigenetic alterations are expected to have relevance for early detection, diagnosis, outcome prediction, and tumor response to therapy. Additionally, epi-drugs as therapeutic modalities may lead to the recovery of genes delaying tumor growth, thus increasing survival rates, and may be effective against tumors without druggable mutations. Epigenetic changes involve DNA methylation, histone modifications, and the activity of non-coding RNAs, causing gene expression changes and their mutual interactions. This systematic review, based on 110 studies, gives a comprehensive overview of new perspectives on diagnostic (28 studies) and prognostic (25 studies) epigenetic biomarkers, as well as epigenetic treatment options (57 studies) for non-small-cell lung cancer. This paper outlines the crosstalk between epigenetic and genetic factors as well as elucidates clinical contexts including epigenetic treatments, such as dietary supplements and food additives, which serve as anti-carcinogenic compounds and regulators of cellular epigenetics and which are used to reduce toxicity. Furthermore, a future-oriented exploration of epigenetic studies in NSCLC is presented. The findings suggest that additional studies are necessary to comprehend the mechanisms of epigenetic changes and investigate biomarkers, response rates, and tailored combinations of treatments. In the future, epigenetics could have the potential to become an integral part of diagnostics, prognostics, and personalized treatment in NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Epigenesis, Genetic; DNA Methylation
PubMed: 36980246
DOI: 10.3390/cells12060905 -
Toxics Dec 2023A growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that... (Review)
Review
Methylomic, Proteomic, and Metabolomic Correlates of Traffic-Related Air Pollution in the Context of Cardiorespiratory Health: A Systematic Review, Pathway Analysis, and Network Analysis.
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 to 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: 38133415
DOI: 10.3390/toxics11121014