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Frontiers in Cardiovascular Medicine 2022Myocardial infarction is the leading cause of death and disability worldwide, and the development of new treatments can help reduce the size of myocardial infarction and...
Myocardial infarction is the leading cause of death and disability worldwide, and the development of new treatments can help reduce the size of myocardial infarction and prevent adverse cardiovascular events. Cardiac repair after myocardial infarction can effectively remove necrotic tissue, induce neovascularization, and ultimately replace granulation tissue. Cardiac inflammation is the primary determinant of whether beneficial cardiac repair occurs after myocardial infarction. Immune cells mediate inflammatory responses and play a dual role in injury and protection during cardiac repair. After myocardial infarction, genetic ablation or blocking of anti-inflammatory pathways is often harmful. However, enhancing endogenous anti-inflammatory pathways or blocking endogenous pro-inflammatory pathways may improve cardiac repair after myocardial infarction. A deficiency of neutrophils or monocytes does not improve overall cardiac function after myocardial infarction but worsens it and aggravates cardiac fibrosis. Several factors are critical in regulating inflammatory genes and immune cells' phenotypes, including DNA methylation, histone modifications, and non-coding RNAs. Therefore, strict control and timely suppression of the inflammatory response, finding a balance between inflammatory cells, preventing excessive tissue degradation, and avoiding infarct expansion can effectively reduce the occurrence of adverse cardiovascular events after myocardial infarction. This article reviews the involvement of neutrophils, monocytes, macrophages, and regulatory T cells in cardiac repair after myocardial infarction. After myocardial infarction, neutrophils are the first to be recruited to the damaged site to engulf necrotic cell debris and secrete chemokines that enhance monocyte recruitment. Monocytes then infiltrate the infarct site and differentiate into macrophages and they release proteases and cytokines that are harmful to surviving myocardial cells in the pre-infarct period. As time progresses, apoptotic neutrophils are cleared, the recruitment of anti-inflammatory monocyte subsets, the polarization of macrophages toward the repair phenotype, and infiltration of regulatory T cells, which secrete anti-inflammatory factors that stimulate angiogenesis and granulation tissue formation for cardiac repair. We also explored how epigenetic modifications regulate the phenotype of inflammatory genes and immune cells to promote cardiac repair after myocardial infarction. This paper also elucidates the roles of alarmin S100A8/A9, secreted frizzled-related protein 1, and podoplanin in the inflammatory response and cardiac repair after myocardial infarction.
PubMed: 36698953
DOI: 10.3389/fcvm.2022.1077290 -
Systematic Reviews Jan 2023Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Diagnostic criteria for typical Rett syndrome require a period of regression, followed by recovery or stabilization, and fulfillment of all four main criteria (loss of purposeful hand skills, loss of spoken language, gait abnormalities, and stereotypic hand movements). Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex.
METHODS
We conducted a search of PubMed, Embase, Web of Science, Cochrane Library, LILACS, and LIVIVO to retrieve studies published in English between Jan. 1, 2000, and June 30, 2021. Pooled prevalence with a 95% confidence interval (CI) was estimated using a random-effects meta-analysis based on a generalized linear mixed model with a logit link.
RESULTS
Ten eligible studies were identified (all in females), with a combined sample size of 9.57 million women and 673 Rett syndrome cases. The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p < 0.001). Despite greatly variable precision of estimation, all estimates were compatible with a prevalence range of approximately 5 to 10 cases per 100,000 females based on their respective 95% CIs.
CONCLUSION
These findings may facilitate planning of therapeutic trials in this indication in terms of target sample size and accrual times.
Topics: Humans; Female; Rett Syndrome; Methyl-CpG-Binding Protein 2; Prevalence; Mutation
PubMed: 36642718
DOI: 10.1186/s13643-023-02169-6 -
Frontiers in Pharmacology 2022Advanced ovarian cancer (AOC) develops rapidly, adding to difficulties in treatment. Traditional Chinese medicine (TCM) plays a significant role in the treatment of...
Advanced ovarian cancer (AOC) develops rapidly, adding to difficulties in treatment. Traditional Chinese medicine (TCM) plays a significant role in the treatment of AOC, and so to explore the efficacy and safety of TCM in the treatment of AOC and its effective targets, we performed the following review. The major databases were searched for randomized controlled trials of TCM for the treatment of AOC. A meta-analysis of the efficacy of Chinese herbs on AOC was conducted using RevMan 5.4 software. Active compounds and target genes were acquired using the TCMSP database. The main targets of AOC were obtained through the GenCards, OMIM, TTD, and DrugBank databases. A protein-protein interaction network carried out on the STRING platform was used to select core genes. The Metascape platform was applied to achieve GO and KEGG enrichment analysis. A total of 24 studies were included. Meta-analysis shows the TCM group improved the overall response rate (OR = 2.71; 95% CI = [2.14, 3.44], Z = 8.25, < 0.00001), overall survival (OR = 2.93, 95% CI = [2.03, 4.24], Z = 5.72, < 0.00001), and progression-free survival (OR = 5.36, 95% CI = [5.03, 5.69], Z = 31.88, < 0.00001) of AOC patients, as well as reducing many adverse events. There were 120 compounds, 246 herb target genes, and 1503 disease targets extracted. The 10 most important components were quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, isorhamnetin, hederagenin, stigmasterol, luteolin, 7-O-methylisomucronulatol, and calycosin. The 20 core targets were , , , , , , , , , , , , , , , , , , , and . KEGG enrichment analysis showed that there are many pathways directly related to different types of tumors, such as in pathway cancer and prostate cancer. Our article reveals TCM is effective and safe against AOC and that Chinese herbs exert effects on the disease through multi-target, multi-component, and multi-pathway mechanisms. (www.crd.york.ac.uk/PROSPERO/), identifier (CRD42022369731).
PubMed: 36438791
DOI: 10.3389/fphar.2022.1040641 -
Endocrine Journal Feb 2023Neuroendocrine tumors (NETs) are a type of rare tumor that can occur at multiple organs. Rectal NETs are the most common NETs in gastrointestinal tract. Due to the...
Neuroendocrine tumors (NETs) are a type of rare tumor that can occur at multiple organs. Rectal NETs are the most common NETs in gastrointestinal tract. Due to the rarity of rectal NETs in rectal cancer, the molecular features and the correlation with patient therapeutic response and prognosis have not been investigated in detail. In this review, we focused on the molecular features, potential therapeutic targets and prognosis of rectal NETs. By summarizing the relevant studies, we established the mutational landscape of rectal NETs and identified a series of large fragment variations. Driver genes including TP53, APC, KRAS, BRAF, RB1, CDKN2A and PTEN were found as the top mutated genes. Large fragment alterations mainly involved known driver genes, including APC, TP53, CCNE1, MYC, TERT, RB1 and ATM. Germline mutations of APC, MUTYH, MSH6, MLH1 and MSH2 associated with Lynch syndrome or FAP were also found in rectal NETs. The BRAF-V600E mutation was reported as an actionable target in rectal NETs, and the combined BRAF/MEK inhibitors were found to be effective targeting BRAF-V600E in advanced or metastatic NETs. The known prognostic risk factors of rectal adenocarcinoma, including a series of demographic and clinicopathological factors were also prognostic factors for rectal NETs. Furthermore, three types of markers, including genetic alterations, protein expression levels and methylation, were also suggested as prognostic factors for rectal NETs. In summary, we established the landscape of mutations and large-fragment alterations of rectal NETs, and identified potential therapeutic targets and a series of prognostic factors. Future studies may focus on the optimization of therapeutic strategies based on potential actionable biomarkers.
Topics: Humans; Proto-Oncogene Proteins B-raf; Neuroendocrine Tumors; Rectal Neoplasms; Mutation; Prognosis; Biomarkers, Tumor
PubMed: 36403965
DOI: 10.1507/endocrj.EJ22-0262 -
BMC Neurology Nov 2022Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of...
BACKGROUND
Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of clinical and imaging characteristics as well as of antibody dynamics.
CASE PRESENTATION
We report a 32-year-old male patient who presented with psychosis, decreased consciousness and movement disorders and was tested positive for anti-NMDA receptor antibodies. Forty-four months after symptom onset and diagnosis of autoimmune encephalitis, he suffered from relapse. At this time, the patient developed anti-MOG and anti-Caspr2 antibodies. Treatment with plasmapheresis, steroids and rituximab eventually led to substantial clinical and radiological improvement. Anti-Caspr2 antibodies persisted, anti-NMDA receptor antibodies decreased, while anti-MOG antibodies turned negative again.
CONCLUSION
We provide long-term longitudinal follow-up of a patient with anti-NMDA receptor encephalitis who developed triple antibody positivity at the time of relapse. Antibody dynamics were associated with clinical disease course.
Topics: Male; Humans; Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Myelin-Oligodendrocyte Glycoprotein; Follow-Up Studies; Autoantibodies; Neoplasm Recurrence, Local; Receptors, N-Methyl-D-Aspartate; Demyelinating Diseases
PubMed: 36384491
DOI: 10.1186/s12883-022-02974-x -
Clinical Genitourinary Cancer Feb 2023Numerous studies suggested methylation modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted DNA methylation... (Meta-Analysis)
Meta-Analysis
PURPOSE
Numerous studies suggested methylation modifications play an important role in upper tract urothelial carcinoma (UTUC), but few have depicted DNA methylation architecture on the pathological process of UTUC. We aimed to better understand the pathogenesis of UTUC and provide precision medicine references when managing UTUC patients.
METHODS
PubMed, Cochrane Library, EMBASE, and Scopus were searched for UTUC until December 31, 2020. Methodological quality assessment was conducted according to NIH recommendations. Meta-analysis was conducted to assess the prognostic effect of methylated genes. Kaplan-Meier survival analyses were performed to validate methylated genes and cytosine-phosphate-guanine (CpG) sites.
RESULTS
Eleven studies (3619 patients) were eligible to investigate 12 methylated genes and 10 CpGs. The quality of all the studies was fair to good. Meta-analysis found the pooled effect of eligible methylated genes had a low risk of tumor recurrence (HR = 0·67; 95% CI: 0·51-0·87; P = ·003), but a high risk of tumor progression (HR = 1·60; 95% CI: 1·17-2·18; P = ·003) and cancer-specific mortality (HR = 1·35; 95% CI: 1·06-1·72; P = ·01). For individual methylation status of GDF15, HSPA2, RASSF1A, TMEFF2, and VIM, the pooled effect of each gene was found pleiotropic on both diagnosis and prognosis. Survival analysis suggested higher methylation of SPARCL1 had a better disease-specific survival (P = ·048).
CONCLUSION
We combined meta-analysis and Kaplan-Meier survival analysis using the most updated evidence on the methylation of UTUC. Candidate biomarkers with essential diagnosis and prognosis function might provide precision medicine references for personalized therapies.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; DNA Methylation; Neoplasm Recurrence, Local; Prognosis; Urologic Neoplasms; Membrane Proteins; Neoplasm Proteins
PubMed: 36376170
DOI: 10.1016/j.clgc.2022.10.008 -
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 -
International Journal of Molecular... Oct 2022The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for... (Review)
Review
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: , , , , , , and in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. , , , and genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
Topics: Biomarkers; Ceruloplasmin; Cross-Sectional Studies; DNA Methylation; Dyslipidemias; Gene Expression; Humans; Myeloid Differentiation Factor 88; Periodontitis; RNA
PubMed: 36233348
DOI: 10.3390/ijms231912042 -
Heliyon Oct 2022DNA methylation is an effective epigenetic process that is frequently linked to changes in gene expression. Zinc is a vital micronutrient that plays a crucial role in...
BACKGROUND
DNA methylation is an effective epigenetic process that is frequently linked to changes in gene expression. Zinc is a vital micronutrient that plays a crucial role in DNA methylation. Therefore, abnormal zinc levels may cause aberrant DNA methylation and other diseases.
OBJECTIVES
To investigate the influence of zinc on gene-specific and global DNA methylation in humans and rodents, their tissues and their cells.
METHOD
Systematic literature searches were conducted using Medline, Scopus, Google Scholar, and Web of Science databases. Studies that met the inclusion criteria and were published in English language were included. Data including the first author, sample size, subjects, targeted genes, tissue types or cells analysed, zinc level, molecular techniques, DNA methylation outcomes, and consequences were extracted.
RESULTS
From a total of 2360 articles screened by title and abstract, 15 met the inclusion criteria. Qualitative analysis indicates that there are associations between zinc deficiency and gene-specific hypomethylation in humans and between zinc deficiency and hypermethylation in rodents. Zinc did not influence LINE-1 methylation in humans. Depending on cell type, zinc could have a positive or negative effect on global methylation in humans and rodents. As predicted, in general, gene expression was elevated by DNA hypomethylation and the corresponding protein levels were also upregulated. However, some studies showed that zinc deficiency led to reduced gene expression or no alteration in mRNA levels and corresponding protein levels.
CONCLUSION
Our study shows links between zinc levels and DNA methylation. However, greater significance may be achieved if more than one independent investigator analyses the same set of genes in the same cell type. Therefore, gene-cell and animal-specific investigations are recommended to reduce variability and allow comparisons across studies.
PubMed: 36203899
DOI: 10.1016/j.heliyon.2022.e10815 -
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