Association of genetic and epigenetic modification in MTHFR gene with coronary artery disease patients in North Indian population

Background: Methylene tetra hydro folate reductase (MTHFR) gene polymorphism C677T (rs180113) and DNA methylation in promoter region of MTHFR gene may contribute to the development of coronary artery disease however the results have been inconsistent across studies with different populations, so the aim of our study is to explore the association of polymorphism in MTHFR gene and methylation in promoter region with coronary artery disease (CAD) and other risk factor (lipid profile, homocysteine, vitamin B12 and folic acid levels) leading to CAD in of north Indian population. Methods: Total 100 CAD patients and 100 healthy controls were enrolled in the study. Genotyping of rs1801133 SNP (C677T) is done by PCR-RFLP and DNA methylation study in promoter region by methylation specific PCR. Lipid profile analysis by automated chemistry analyzers, serum homocysteine, folic acid and vitamin B12 was assayed by ELISA. Results: As per our finding the T allele (OR=3.03, 95% CI=1.74-5.27) and hyper methylation in promoter region of MTHFR increases the odds of coronary artery disease, (OR=3.05, 95% CI=1.7-5.6). Study participants with CT and TT genotype had significantly higher homocysteine (Hcy) (p=0.001), lower folic acid level (p=0.0), and HDL levels (p<0.0001) than those with CC genotype. The study subjects with hyper methylated promoter region have a significantly high homocystenemia levels (p=0.001). Conclusions: The TT genotype of the MTHFR C677T gene polymorphism and hyper methylation in promoter region of MTHFR, is associated with CAD and can be useful in identification of new biomarkers, development of preventive and therapeutic strategies for CAD.

Decrease of 5-hydroxymethylcytosine in primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphoproliferative disorder

Abstract Background: Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, it has rarely been studied in cutaneous lymphomas. Objectives: The authors aimed to explore the role of differential 5-hmC immunostaining as a useful marker to distinguish PC-SMTLD from PL. Methods: Retrospective case series study with immunohistochemical and immunofluorescence analysis of 5-hmC was performed in PL and PC-SMTLD. Results: Significant decrease of 5-hmC nuclear staining was observed in PC-SMTLD when compared with PL (p<0.0001). By semi-quantitative grade integration, there were statistical differences in the final 5-hmC scores in the two study groups. The IF co-staining of 5-hmC with CD4 revealed a decrease of 5-hmC in CD4+ lymphocytes of PC-SMTLD. Study limitations: The small clinical sample size of the study. Conclusions: The immunorreactivity of 5-hmC in CD4+ lymphocytes was highly suggestive of a benign process as PL. Furthermore, the decrease of 5-hmC nuclear staining in PC-SMTLD indicated its lymphoproliferative status and helped to make the differential diagnosis with PL. © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Research progress on m5C methylation and its prospects in tumor immunotherapy / 口腔疾病防治

@#Epigenetic modification plays an important role in the biological regulatory process of eukaryotic cells. Tumor immunotherapy is an important means and clinical strategy for the treatment of some cancers. 5-Methylcytosine (m5C) is an important component of the epigenetic regulatory network discovered after m6A and has become a new topic for life science research in recent years. The m5C methylation of RNA can affect the fate of the modified RNA molecules and play an important role in various biological processes, including RNA stability, protein synthesis and transcriptional regulation. Recent studies have shown that m5C writers, erasers and readers are related to a variety of cellular biological processes and systemic diseases, including the occurrence, metastasis and tumor immune microenvironment. m5C methylation can widely affect gene expression and the biological process of tumorigenesis and development at multiple levels, but its specific mechanism and potential interaction with other epigenetic modifications in tumor immunotherapy are still unclear, and its regulatory mechanism, risk assessment and role in targeted therapy for malignant tumors need to be further studied. This article will review the dynamic regulatory network of m5C, the biological role of m5C modification in solid tumors and potential targets in tumor immunotherapy.

Effects of 5G mobile phone radiofrequency radiation exposure on male mouse fertility / 中国辐射卫生

Objective To clarify the effects of 5G mobile phone radiofrequency radiation exposure on male mouse fertility and to preliminarily explore the underlying mechanisms. Methods Healthy male C57BL/6 mice aged 7-8 weeks were randomly assigned to Sham group, 3.5 GHz radiofrequency radiation group, and 4.9 GHz radiofrequency radiation group, with 16 mice in each group. The mice were exposed to 3.5 GHz or 4.9 GHz mobile phone radiofrequency radiation for 42 consecutive days (1 h per day). The sperm quality was evaluated using sperm count, deformity rate, and motility. H&E staining was performed to assess testicular tissue structure by observing the morphology of spermatogenic cells at various development stages, the diameter of seminiferous tubules, and the thickness of seminiferous epithelium. The sperm mitochondrial function was assessed using sperm mitochondrial membrane potential and testicular ATP content. The fertility of mice was evaluated through fertility rate, litter size, and survival rate of offspring. The underlying mechanisms were explored by detecting the methylation of LRGUK gene and its mRNA and protein levels. Results Compared with the Sham group, there were no significant changes in sperm count in the 3.5 GHz and 4.9 GHz groups; however, the sperm abnormality rate significantly increased (P < 0.05) and sperm motility significantly decreased (P < 0.05). The structure of testicular tissue, the function of sperm mitochondria, and fertility of mice showed no significant changes as compared with the Sham group. The methylation level of LRGUK gene in the testes significantly increased, while the mRNA and protein expression levels significantly decreased. Conclusion Exposure to 3.5 GHz and 4.9 GHz mobile phone radiofrequency radiation for 42 consecutive days can lead to an increase in sperm deformity rate and a decrease in sperm motility in mice, but has no significant effect on fertility, which may be related to an increase in methylation level of the LRGUK gene in the testes.

The value of GNB4 and Riplet gene methylation detection in the diagnosis of primary liver cancer / 安徽医科大学学报

Objective To investigate the diagnostic efficacy and clinical value of GNB4 and Riplet gene methylation alone and in combination in the diagnosis of primary liver cancer.Methods A total of 313 patients were selected,including 78 patients with primary liver cancer,41 patients with other digestive system tumors,17 patients with non-digestive system tumors,20 patients with postoperative liver cancer,and 157 patients with benign liver disea-ses.The levels of GNB4 and Riplet gene methylation in plasma were detected using quantitative methylation-specific PCR(qMSP).Serum alpha-fetoprotein(AFP)levels were measured by direct chemiluminescence.Results The sensitivity and specificity of AFP in diagnosis were 51.3％and 94.3％,respectively;the sensitivity and specificity of GNB4 gene methylation in diagnosis were 83.3％and 99.4％,respectively;the sensitivity and specificity of Riplet gene methylation in diagnosis were 73.1％and 99.4％,respectively.The sensitivity and specificity of GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of combined diagnosis including age and gender were 93.6％and 97.5％,respective-ly.Conclusion The sensitivity and specificity of AFP in the diagnosis of primary liver cancer are limited,while the methylation levels of GNB4 and Riplet genes are higher,and the sensitivity and specificity of their combined de-tection are higher than those of AFP.The sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis are significantly higher than those of AFP,GNB4 and Riplet gene methylation alone.

Combined detection of PAX1 methylation and p16/Ki-67 dual staining improves diagnostic performance for atypical squamous cells in cervical cancer / 陆军军医大学学报

Objective To compare paired boxed gene 1(PAX1)methylation and p16/Ki-67 double staining alone and in combination in thinprep cytologic test(TCT)for distinguishing atypical squamous cells of undetermined significance(ASC-US)and low-grade squamous intraepithelial lesion(LSIL)population.Methods A total of 247 patients with TCT results of ASC-US and LSIL admitted in our hospital from January 2021 to December 2022 were enrolled in this study.Detection efficacy of PAX1 methylation and p16/Ki-67 double staining alone and in combination was evaluated with colposcopic pathologic results as the gold standard and the sensitivity,specificity,accuracy and area under the curve(AUC)as evaluation indexes.Results The positive rates of PAX1 methylation and p16/Ki-67 double staining were increased with the severity of pathological findings.Combined detection of PAX1 methylation and p16/Ki-67 assay had a sensitivity of 91.25％,specificity of 97.72％and accuracy of 95.51％in the women with TCT of ASC-US,and these values were statistically better than those of PAX1 methylation and p16/Ki-67 double staining alone(P＜0.01).Conclusion The combination of PAX1 methylation and p16/Ki-67 double-staining assay can further improve the diagnostic efficacy in patients with ASC-US on TCT results.

Clinical applications of abnormal DNA methylation in chronic myeloid leukemia / 中南大学学报(医学版)

DNA methylation,a crucial biochemical process within the human body,fundamentally alters gene expression without modifying the DNA sequence,resulting in stable changes.The changes in DNA methylation are closely related to numerous biological processes including cellular proliferation and differentiation,embryonic development,and the occurrence of immune diseases and tumor.Specifically,abnormal DNA methylation plays a crucial role in the formation,progression,and prognosis of chronic myeloid leukemia(CML).Moreover,DNA methylation offers substantial potential for diagnosing and treating CML.Accordingly,understanding the precise mechanism of DNA methylation,particularly abnormal changes in the methylation of specific genes in CML,can potentially promote the development of novel targeted therapeutic strategies.Such strategies could transform into clinical practice,effectively aiding diagnosis and treatment of CML patients.

Differential analysis of DNA methylation combined with gene expression in patients with pulmonary embolism / 中华急诊医学杂志

Objective:To screen genetic and epigenetic expression differences associated with pulmonary embolism through integrated bioinformatics analysis.Methods:Four patients with pulmonary embolism and healthy physical examination in the Third Affiliated Hospital of Xinjiang Medical University in 2019 were selected as the research objects, using high-throughput sequencing technologies and methylation chip technology to detect, screening and integrated peripheral blood difference genomes and the epigenome data to identify the pathogenesis of pulmonary embolism caused by methylation of drive and differentially expressed genes, GO and KEGG enrichment analysis were performed.Results:Coexpression analysis of DNA methylation and gene expression data between the pulmonary embolism group and the healthy control group showed that differential methylation in the upstream region of genes was negatively correlated with gene expression. Among them, 8 significantly methylated genes in the upstream region of genes were screened out, and independent sample t-test and Pearson correlation analysis were done. In the pulmonary embolism group, there were 6 significant methylated genes of TSS1500, namely TSPO2, C1QA, AQP1, TNFSF9, MIA and STAB1, and the differential expression multiple log2FC of corresponding genes was 1.298, 1.629, 1.024, 2.746, 2.539, 1.060, respectively. The correlation between gene expression and gene methylation were -0.908, -0.900, -0.824, -0.784, -0.783, -0.779, respectively, and the methylation differences between the two groups were -0.049, -0.053, -0.048, -0.057, -0.050, respectively. -0.053 ( P < 0.05). There were three significantly methylated genes in the TSS200 region, namely TSPO2, SLC9A, and SIGLEC1. The gene expression differential multiple log2FC was 1.298, -2.252, and 1.866, respectively. The correlation between gene expression and gene methylation was -0.860, -0.774, and -0.739, respectively. The methylation difference between the two groups was -0.051, 0.027, -0.048 ( P < 0.05). In the pulmonary embolism group, 7 genes, including TSPO2, C1QA, AQP1, TNFSF9, MIA, STAB1 and SIGLEC1, showed hypomethylation and high expression in the TSS region. SLC9A3 gene showed high methylation and low expression. In the analysis of GO function, significant enrichment was obtained in complement activation, immune response and activation protein cascade. In the KEGG signaling pathway, the immune system, bacterial infection, and signaling molecules and interactions are significantly enriched, thereby regulating the occurrence of pulmonary embolism. Conclusions:Based on the combined analysis of DNA methylation and gene expression, a new idea of the occurrence and development of pulmonary embolism has been found, which can be further studied in the future.

Value of SHOX2 and RASSF1A Gene Methylation in Alveolar Lavage Fluid in Patients with Pulmonary Nodules or Masses in the Diagnosis of Lung Cancer / 昆明医科大学学报

Objective The diagnostic efficacy of the two gene methylation indexes was verified by lung biopsy or postoperative disease examination results.Methods A prospective study was conducted to collect 99 patients diagnosed with pulmonary nodules and masses in the Third People's Hospital of Yunnan Province from March 2019 to March 2020.After bronchoscopy and BALF samples were collected,regular follow-up,lung puncture biopsy and post-operative disease examination were performed.Results Ninety-nine patients with pulmonary nodules and masses were divided into lung cancer group(n = 50)and benign lung disease group(n = 49)after pathological diagnosis.The age of patients in the lung cancer group was(62.64±9.71)years,and that of the benign lung disease group was(60.48±13.69)years,and there was a statistical difference between the two groups(P = 0.032).In the diagnosis of lung cancer,the sensitivity and specificity of SHOX2 and RASSF1A genes alone were found to be 72%and 58%,respectively,and 92.3%and 95.9%,respectively.The combined test of the two genes showed a higher sensitivity in the diagnosis of lung cancer,0.84,compared to 0.102 in the benign disease group(P<0.001).ROC curve analysis showed that the sensitivity of the two genes could be increased to 84%when methylation was combined.Conclusion The methylation test of SHOX2 and RASS1A gene in alveolar lavage fluid has a good value in the diagnosis of lung cancer patients with pulmonary nodules and masses and SHOX2 combined with RASSF1A can be an important supplementary tool for early diagnosis of lung cancer when imaging and histological diagnosis are unclear.

Predictive Value of Peripheral Blood Septin9 Gene Methylation Assay in Colorectal Adenoma / 昆明医科大学学报

Objective To investigate the predictive significance of Septin9 gene methylation(mSEPT9)in peripheral blood in the diagnosis of colorectal adenoma.Methods A total of 52 subjects were included,31 patients with colorectal adenomas were collected as the experimental group in the Department of Pathology and 21 subjects with negative colonoscopy in the gastroenterology outpatient clinic were used as the control group from October 2020 to May 2022.mSEPT9 was detected in the two groups,and the results of CEA level in peripheral blood were collected.All the results were statistically analyzed using the Receiver Operating Characteristic(ROC).Results The area under the curve(area of the ROC:AUC)of mSEPT9detectionto predict the development of adenoma was 0.7205(P<0.05),And the cut-off value(CT value)was 39.55,the corresponding sensitivity was 90.91%and the specificity was 56.67%.The AUC of CEA detection for predicting adenoma was 0.5333(P>0.05).Conclusions The detection of mSEPT9 is better than that of CEA tumor marker detection in peripheral blood for screening colorectal adenomas with good sensitivity and relative specificity.Invasive colonoscopy for people with positive mSEPT9 screening results can be easier to accept by the general population.

Correlation between DKK1 promoter methylation level and diabetic microangiopathopathy complicated with osteoporosis / 中华内分泌外科杂志

Objective:To investigate the correlation between the promoter methylation level of Dickkopf-related protein 1 (DKK1) gene and diabetic microangiopaopathy complicated with osteoporosis.Methods:Patients with type 2 diabetes mellitus (T2DM) microangiopathopathy who were admitted to our hospital from Jan. 2019 to Dec. 2022 were collected as research objects, and divided into observation group (44 cases) and control group (58 cases) according to whether they were complicated with osteoporosis. Bone mineral density (BMD) of lumbar spine (L1-4) was measured, and bone metabolism indexes, including serum calcium, serum phosphorus, 25-hydroxy vitamin D3[25-hydroxy vitamin D3, 25- (OH) D3], PTH, C-terminal telopeptide of typeI collagen (CTX), procollagen of aminoterminal propeptide (PINP) and tartrate resistant acid phosphatase (TRACP) levels were detected; The promoter methylation level of DKK1 gene was determined.Results:The methylation level of DKK1 gene promoter in the observation group was 5.17%±0.73%, which was significantly higher than that in the control group (3.81%±0.61%), with statistical significance ( t=5.22, P<0.001). The 25- (OH) D3 level, PTH and lumbar bone density in the observation group were significantly lower than those in the control group, while the CTX and TRACP levels were significantly higher than those in the control group ( t was 5.58, 4.35, 4.12, 4.05 and 4.17, respectively, P<0.001). In all patients, the promoter methylation level of DKK1 gene was significantly positively correlated with CTX and TRACP ( r was 0.41 and 0.39, P was 0.006 and 0.027, respectively), and significantly negatively correlated with PTH and lumbar bone density ( r was -0.38 and -0.43, respectively). P=0.015 and 0.003, respectively). ROC curve analysis showed that the area under the curve of DKK1 methylation level to distinguish type 2 diabetes microangionopathy with and without osteoporosis was 0.841 (0.762-0.921), and the sensitivity and specificity were 86.4% and 72.4%, respectively. Conclusion:The methylation level of DKK1 gene promoter is associated with osteoporosis and bone metabolism in T2DM patients with microangiopathia.

Research progress of m6A methylation modification in regulating tumor immunity / 上海交通大学学报（医学版）

N6-methyladenosine(m6A)is the most prevalent modification that regulates gene expression in eukaryotes.It regulates splicing,degradation,stability,and translation of RNA.Numerous studies have demonstrated the close association between m6A methylation and tumor development,highlighting its crucial role in regulating tumor immune response.The m6A modification actively participates in governing immune cell differentiation and maturation as well as modulating anti-tumor immune responses.Within the tumor microenvironment,m6A modification can also impact the recruitment,activation,and polarization of immune cells,thereby either promoting or inhibiting tumor cell proliferation and metastasis.Consequently,it plays a pivotal role in reshaping the tumor immune microenvironment.In recent years,immunotherapy for tumors has been increasingly applied to clinical practice with notable success achieved through approaches such as immune checkpoint inhibitor therapy and adoptive cell immunotherapy.Targeting m6A modifications to interfere with the immune system,such as targeting dysregulated m6A regulators through small molecule inhibitors and inducing immune cell reprogramming,can improve anti-tumor immune response and strengthen immune cells' ability to recognize and kill tumor cells.The m6A modification represents a novel avenue for potential clinical application within tumor immunotherapy.This review provides a comprehensive summary of the regulatory impact of m6A methylation modification on immune cells in the context of cancer,while also delving into novel targets for tumor immunotherapy.

Advances in epigenetics of nonalcoholic fatty liver desease / 复旦学报（医学版）

Nonalcoholic fatty liver disease(NAFLD)is a metabolic liver disease that ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis(NASH).NASH is characterized by persistent liver damage,inflammation,and fibrosis which significantly increases the risk of end-stage liver diseases,such as liver cirrhosis and hepatocellular carcinoma.The pathogenesis of NAFLD/NASH is not yet fully understood,but its recent epigenetic advances have provided new insights into the mechanisms of this disease.This review summarized recent progress in this area which has laid a solid foundation for elucidating the pathogenesis of NAFLD and provides potential targets for early detection,diagnosis,and treatment of this disease.

Research progress on the relationship between m6A methylation modification and acute kidney injury / 实用医学杂志

Acute kidney injury(AKI)is a global public health problem with high morbidity,high mortality and costly treatment cost.The pathogenesis of AKI is very complex,and the treatment strategies for AKI are lim-ited,then it is very matter to explore the pathophysiological mechanism and potential therapeutic targets of acute kidney injury.N6-methyladenosine(m6A)is the most abundant and extremely conservative epigenetic modification in eukaryotic,which is a dynamic and reversible process involving in splicing,nuclear export,translation,stabil-ity,and higher structure of RNA,and regulated by three regulatory factors:methyltransferase,demethylase and methylated reading protein.Current studies have found that m6A plays an important regulatory role in AKI and can be a potential therapeutic target for AKI.In this review,we provide a brief description of m6A and summarize the impact of m6A on AKI and possible future study directions for this research.

The value of urine protein kinase Y-linked gene promoter site methylation in early diagnosis of prostate cancer / 实用医学杂志

Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

Research progress of RNA m6A methylation in post-stroke cognitive impairment / 天津医药

Post-stroke cognitive impairment(PSCI)is mainly manifested as learning and memory disorders.Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation.Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI,it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI.This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation,which will provide reference for researchers in this field.

Effects of different exercise types on human DNA damage,DNA methylation and telomere length / 中国组织工程研究

BACKGROUND:Exercise is not only an effective means to improve physical and mental health,but also has a good intervention effect on the occurrence and development of metabolic,cardiovascular and cerebrovascular diseases.The reason is related to the epigenetic factors. OBJECTIVE:To summarize the effects of different exercise types on human DNA damage,DNA methylation,and telomere length,and analyze the possible mechanism of exercise regulation epigenetic modification,in order to provide a reference for exercise to improve body function. METHODS:"Exercise,aerobic training,acute exercise,anaerobic training,resistance training,DNA damage,DNA methylation,telomere"were used as the Chinese search terms,and"exercise,sport,aerobic exercise,anaerobic exercise,resistance training,acute exercise,DNA metabolism,DNA damage,telomere"were used as the English search terms.We searched PubMed,Embase,Web of Science,and CNKI databases,and screened articles according to inclusion and exclusion criteria,and finally included 70 articles. RESULTS AND CONCLUSION:(1)Long-term aerobic,resistance,and anaerobic exercises can improve DNA damage.The reason is that exercise can improve the body's antioxidant capacity.Acute exercise can aggravate the degree of DNA damage by up-regulating the expression of reactive oxygen species and reactive nitrogen oxides.(2)Acute exercise,long-term resistance exercise,and anaerobic exercise play a positive role in reducing DNA methylation.The key mechanism may be that exercise-induced reactive oxygen species changes the expression of glutathione oxidized/glutathione,DNA methyltransferase,and 10-11 translocation enzyme.Then it can regulate DNA methylation.(3)Compared with other types of exercise,long-term aerobic exercise may have more potential value in increasing telomere length,and its biological mechanism involves inflammation,oxidative stress,DNA methylation,and regulation of microRNAs(miRNAs)expression.(4)Based on the current literature,aerobic exercise lasting at least 2 years can increase telomere length,and future research should further clarify the optimal exercise duration.

Progress in epigenetic regulation of vascular smooth muscle cell remodeling in the occurrence and development of aortic aneurysms / 中国组织工程研究

BACKGROUND:Epigenetics,as an important regulation mode of gene expression network,has been proved to play an important role in the occurrence and development of aortic aneurysm mediated by vascular smooth muscle cell remodeling. OBJECTIVE:To review the epigenetic regulation mechanism underlying vascular smooth muscle cell remodeling during the occurrence and progression of aortic aneurysm. METHODS:Related articles published from 1970 to 2022 were retrieved from PubMed,Web of Science and CNKI databases.The keywords were"Aortic aneurysm,Vascular smooth muscle,Smooth muscle cells,Epigenetic,DNA methylation,Histone modification,Non coding RNA"in English and Chinese.Ultimately,we included 71 articles for review. RESULTS AND CONCLUSION:Epigenetic modification can influence the occurrence and progression of aortic aneurysm by targeting vascular smooth muscle cell remodeling and extracellular matrix degradation.Targeted epigenetic modification can play a key role in aortic aneurysm treatment,delaying the disease and improving the prognosis.Epigenetic related enzymes,such as DNA methylesterases and histone-modifying enzymes,can influence the progression of aortic aneurysm by regulating vascular smooth muscle cell remodeling,including cell proliferation,migration and apoptosis,and can be used as targets for drug therapy.The research of epigenetic modification on aortic aneurysm is still in the basic research stage and some epigenetic modification mechanisms have not yet been explored.With the development of medical research,targeted epigenetic modification is expected to achieve new breakthroughs in the treatment of aortic aneurysm and clinical transformation.

Identification of differences in N6-methyladenosine-related genes in steroid-induced femoral head necrosis / 中国组织工程研究

BACKGROUND:It is known that N6-methyladenosine(m6A)plays a role in the pathogenesis of various diseases and studies have suggested its involvement in the pathologic changes of steroid-induced femoral head necrosis(SNFH).However,research on m6A methylation modifications in steroid-induced femoral head necrosis is limited. OBJECTIVE:Using bioinformatics methods to identify the differential expression of m6A-related genes in steroid-induced femoral head necrosis and to predict miRNAs associated with these genes to further elucidate the role and mechanism of m6A methylation in steroid-induced femoral head necrosis. METHODS:Differential gene expression between steroid-induced femoral head necrosis and control groups was analyzed using GSE123568 gene expression data and identified using the"limma"package in R.Functional enrichment analysis was performed on the differentially expressed genes.Differential analysis of the related genes was carried out using the"ggstatsplot"package in R.The differential genes were cross-validated using the GSE74089 dataset.An mRNA-miRNA regulatory network was constructed,and co-expression analysis was performed on the module genes followed by enrichment analysis.Differences in immune cell infiltration between steroid-induced femoral head necrosis and control groups were quantified using the ssGSEA method. RESULTS AND CONCLUSION:Correlation analysis revealed 13 m6A-related genes,and further analysis through the protein-protein interaction network identification and receiver operating characteristic curve analysis showed that YTHDF2 was expected to be a core differential gene as a potential early biomarker.Enrichment analysis indicated that differentially expressed genes were mainly involved in inflammation and immune response and were closely related to osteoclasts.Cross-validation analysis showed that differential gene expression results between the two datasets were consistent.mRNA-miRNA regulatory network analysis revealed that YTHDF2 was negatively correlated with miRNA-27a.Immune infiltration analysis revealed an increase in immune cell infiltration in steroid-induced femoral head necrosis,and YTHDF2 was positively correlated with the infiltration of CD4+T cells.To conclude,m6A-related gene YTHDF2 can serve as a potential biomarker of steroid-induced femoral head necrosis and is valuable for the early clinical diagnosis and treatment of steroid-induced femoral head necrosis.The negative correlation between YTHDF2 and mir-27a and the positive correlation between YTHDF2 and CD4+T cell infiltration provide new insights into the early diagnosis and treatment of steroid-induced femoral head necrosis and shed light on the mechanism of m6A in steroid-induced femoral head necrosis.

Mechanism of m6A methylation regulating bone metabolism for prevention and treatment of osteoporosis / 中国组织工程研究

BACKGROUND:The pathogenesis of osteoporosis is complex,and its essence is the weakening of bone formation and the enhancement of bone absorption caused by various reasons,resulting in the imbalance of bone metabolism.In recent years,N6-methyladenosine has been found(N6-methyladenosine,m6A)methylation can prevent and treat osteoporosis by regulating bone metabolism. OBJECTIVE:Taking the regulation of bone metabolism by m6A methylation as an entry point,to systematically sort out and summarize the research progress of m6A methylation in osteoporosis,so as to provide certain theoretical reference bases for the search of new therapeutic targets for osteoporosis. METHODS:CNKI,WanFang,VIP,PubMed,MEDLINE,Nature,and Cochrane databases were retrieved for relevant literature published from database inception to 2023.The keywords were"osteoporosis,m6A methylation,bone metabolism,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English.Duplicates and obsolete non-referenced documents were excluded,and a total of 73 standard papers were included for further review. RESULTS AND CONCLUSION:m6A methylation can affect the activity and differentiation of bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts through various pathways to regulate bone metabolism and prevent osteoporosis.The regulatory process of m6A methylation is extremely complex,and its related proteins play different roles in different cells.Even in the same kind of cells,the same type of proteins may have radically different roles,regulating different physiological and pathological processes.