Hyper-methylation of Gene Associated with Insensitivity to Arginine Vasopressin in Preeclamptic Placental Vasculature | Medicine and Medical Research: New Perspectives Vol. 1

 

The present study highlights the contractile responses of AVP in normal and pre-eclamptic placental vessels to uncover the distinctive features of placental vascular regulations along with placental pathophysiological changes, as well as the molecular mechanisms of AVP under pre-eclamptic conditions.

 

One of the main causes of maternal morbidity and mortality is pre-eclampsia. Pre-eclampsia is primarily caused by aberrant placental function and circulation, even if the exact mechanisms causing pre-eclampsia are yet unknown. As a potent vasoconstrictor, arginine vasopressin (AVP) has long been associated with regulating placental vascular tone and circulation, and its secretion is significantly elevated in pre-eclamptic circulation. However, little is known about the reactivity of AVP in pre-eclamptic placental vasculature. To uncover the specific characteristics of placental vascular regulations along with placental pathophysiological changes and the corresponding molecular mechanisms under pre-eclamptic conditions, vascular function, and molecular assays were conducted using placental vessel samples from normal and pre-eclamptic pregnancies. The present study found that the vasoconstriction responses of placental vessels to AVP were weakened in pre-eclampsia compared to normal pregnancy. The insensitivity of AVP was correlated with the down-regulated arginine vasopressin receptor 1a (AVPR1A) and protein kinase C isoform \(\beta\) (PKC\(\beta\)), especially the hyper-methylation-mediated down-regulation of the AVPR1A and PKC\(\beta\) genes, respectively. The study findings not only provided new information for comprehending the pathological characteristics of PE but also emphasized the crucial role of epigenetic-mediated gene expression in pre-eclamptic placental vascular dysfunctions. This new and important information may be beneficial for understanding the pathogenesis of PE and for the development of new approaches and treatments for PE.

Author(s) Details

Qinqin Gao
Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Lingjun Li
Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Hongmei Ding
Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China and Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China. 215006, P.R. China.

Huan Li

Ultrasonography Lab, Sheng Xin Branch of Nan'an General Hospital, Nan'an, China.

Jiaqi Tang
Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Meihua Zhang
Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University, Jinan, Shandong, 250014, China.

Ming Li

Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China and Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Miao Sun
Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Zhice Xu
Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

 

Please see the book here:- https://doi.org/10.9734/bpi/mmrnp/v1/1446

Low Prevalence of CpG Island Methylator Phenotype (CIMP) in Ugandan Colorectal Cancer: A Molecular and Clinicopathological Analysis | Chapter 7 | Disease and Health: Research Developments Vol. 9

Introduction: Genetic and epigenetic aberrations are responsible for the development of colorectal cancer (CRC) that are inherited or gained during life, or both. A number of risk factors for CRC have been determined in epidemiologic studies which include age, obesity, race, diet, cigarette smoking, inflammatory bowel disease, family history of colon cancer, intake of alcohol and physical inactivity. A recognized subgroup of colorectal cancer (CRC) known as CpG island methylator phenotype (CIMP) is associated with particular patient outcomes and genetic defects in developed high-income countries. CIMP is a well-defined epigenetic subtype in CRC, but its prevalence in African populations remains understudied. In Uganda, the CIMP status of colorectal cancer has not been determined despite the increase in the incidence of CRC according to the Kampala Cancer Registry. Hence the objective of this cross-sectional study was to determine the CIMP status of colorectal cancer in Ugandan patients.

Methodology: This was a retrospective study carried out between 2008 and 2021 involving formalin fixed paraffin embedded CRC tissue blocks. Next-generation sequencing (NGS) was used to interrogate pathogenic variants which were present in the MMR genes, BRAFV600E and KRAS. The MSI status was also obtained using immunohistochemistry on MLH1, MSH2, MSH6 and PMS2. Targeted NextGen Bisulphite Sequencing was used for CIMP testing based on a validated quantitative DNA methylation assay. We analyzed CIMP status in 92 CRC patients using a 13-gene panel which included APC, CACNA1G (MINT31), CDKN2A, CRABP1, IGF2, IGFBP3, MGMT, RASSF1, SEPTIN9, SFRP2, SOCS1, SV2C(MINT 1), TMEFF1(HPP1), and WIFI. CIMP was defined as ≥6/13 methylated genes.

Results:  Out of 92 cases which had an adequate quantity of DNA to carry out CIMP analysis, 11(11.9%) were CIMP positive and 81(88.0%) were CIMP negative. CIMP-positive tumours represented 3(5.8%) of MSI-positive tumours compared with 8(10.7%) of MSS tumours and this did not reach statistical significance (p=0.516). CIMP was associated with BRAF mutation (p=0.013). There were 7(11.1%) CIMP-positive tumours in the left colon and 4(13.8%) CIMP-positive tumours in the right colon and this did not reach statistical significance (p=0.713). There were 5(3.9%) colorectal tumours having pathologic missense BRAF V600 mutations and 8(6.3%) colorectal tumours having pathologic missense KRAS mutations.

Conclusions: In contrast to Western studies, Ugandan colorectal tumours exhibited low BRAF and KRAS mutation rates. There was a lack of association between MSI and CIMP which differs from global trends. However, in keeping with studies from the West, there was an association between CIMP and BRAF mutation. Compared to Western developed high-income countries, in Uganda the prevalence of CIMP-positive tumours is low. CIMP is a distinct epigenetic subtype of colorectal cancer in Ugandan patients. The low CIMP prevalence suggests potential ethnic or regional variations in CRC pathogenesis, warranting further study.

 

Author (s) Details

 

Richard Wismayer
Department of Surgery, Masaka Regional Referral Hospital, Masaka, Uganda, Department of Surgery, Faculty of Health Sciences, Equator University of Science and Technology, Masaka, Uganda, Department of Surgery, Faculty of Health Sciences, Habib Medical School, IUIU University, Kampala, Uganda, Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda and Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.

 

Rosie Matthews
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.

 

Celina Whalley
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

 

Julius Kiwanuka
Department of Epidemiology and Biostatistics, College of Health Sciences, Makerere University, Kampala, Uganda.

 

Fredrick Elishama Kakembo
Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda and African Centre of Excellence in Bioinformatics and Data Intensive Sciences, Infectious Diseases Institute, Makerere University, Kampala, Uganda.

 

Steve Thorn
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK and Department of Oncology, University of Oxford, Oxford, UK.

 

Henry Wabinga
Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere
University, Kampala, Uganda.

 

Michael Odida

Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK and Department of Pathology, Faculty of Medicine, Gulu University, Gulu, Uganda.

 

Ian Tomlinson
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK and Department of Oncology, University of Oxford, Oxford, UK.

 

Please see the book here:- https://doi.org/10.9734/bpi/dhrd/v9/5137

An Introduction to Epigenetics of Cancer | Book Publisher International

Epigenetics plays a crucial role in cancer development, offering insights into how gene expression is regulated beyond DNA sequence changes. An Introduction to Epigenetics of Cancer explores the fundamental principles of epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, and their impact on tumor initiation, progression, and therapy resistance. This book delves into the mechanisms by which epigenetic alterations contribute to oncogenesis and highlights emerging diagnostic and therapeutic strategies targeting the epigenome. Designed for researchers, clinicians, and students, this book provides a comprehensive yet accessible overview of the dynamic and reversible nature of epigenetic regulation in cancer, emphasizing its potential for innovative treatments and personalized medicine.

 

Author (s) Details

 

Dr. D. Udaya Kumar
Department of Human Genetics, Andhra University, Visakhapatnam, Andhra Pradesh, India.

 

Please see the book here:- https://doi.org/10.9734/bpi/mono/978-93-49238-70-1

 

The Effect of Environmental Factors on the DNA Methylation Pattern and Its Impact on Addiction | Chapter 4 | Advancement and New Understanding in Medical Science Vol. 10

 Substance addiction remains a significant social and medical issue, influenced by both environmental and genetic variables. The interplay between genetic and ecological factors demonstrates the importance of the epigenetic mechanism. Given its ability to control and influence enduring alterations in gene expression, epigenetic regulation provides a compelling hypothesis for the persistent behavioral abnormalities associated with drug addiction. Epigenetic mechanisms, including DNA methylation, significantly influence drug addiction and substance abuse. Environmental factors such as parental influence, cultural norms, media representation, and learned physical associations also contribute to addiction. Nutritional, pharmacological, physical, and psychosocial factors (such as stress exposure) also affect the DNA methylation profile, leading to changes in gene expression and vulnerability to drug addiction. Studies show that genetic predispositions to psychiatric illnesses like addiction vulnerability can be attenuated or regulated by environmental factors. This chapter will focus on the effect of DNA methylation and environmental factors on drug addiction. Understanding these variables could potentially provide interpretive tools for the future diagnosis and management of addiction.

Author(s) Details:

Hemam Raishowriya Devi,
Department of Biotechnology, Manipur University, Canchipur, Imphal-795003, Manipur, India.

Reena Haobam,
Department of Biotechnology, Manipur University, Canchipur, Imphal-795003, Manipur, India.

Please see the link here: https://stm.bookpi.org/ANUMS-V10/article/view/13924

Type 2 Diabetes and Epigenetics: A Comprehensive Review | Chapter 5 | Advancement and New Understanding in Medical Science Vol. 9

Type 2 Diabetes is one of the major public health issues and a complex metabolic disorder strongly associated with genetic predisposition influenced by environmental factors and epigenetic regulation. Around 537 million people were diagnosed as diabetic in 2021 worldwide and it is predicted that the number will rise to 578 million by 2030, and 700 million by 2045. This review paper illustrated the role of epigenetics in the pathogenesis, progression, and detection of Type 2 Diabetes. A review study was performed for the articles published in English from 2000-2023 using Pub Med, and Google Scholar databases. Main underlining mechanisms of Type 2 Diabetes were identified: insulin resistance in the peripheral tissue and disintegrated insulin secretion. Epigenetics is “the study of changes in the gene functions that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence. Genome Wide Association Studies suggested that epigenetic regulation such as DNA methylation, Histone modification, microRNA strongly co-relates the development and progression of Type 2 Diabetes. Altered DNA methylation patterns in pancreatic islets, skeletal muscle, adipose tissue, from diabetic subjects compare to normal subjects was also found. Other risk factors like obesity, age, gender, impaired glucose tolerance, periconception and intrauterine environment may also have been linked with the possibilities of epigenetic changes. Lifestyle, socioeconomic condition, food habits are contributing to obesity and Type 2 Diabetes. Every year 2.8 million people die worldwide due to obesity and its complications. Epigenetics plays a crucial role by modifying the gene expression and establishing a relationship between the environment and genetic factors. Understanding the epigenetic mechanisms contributing to the development of Type 2 Diabetes is still limited.

Author(s) Details:

Abhijeet Roy,
Institute for Biomedical Sciences, Georgia State University, GA, USA and Center for Non-Communicable Diseases and Nutrition, BRAC James P Grant School of Public Health, BRAC University, Bangladesh.

Please see the link here: https://stm.bookpi.org/ANUMS-V9/article/view/13624

Epigenetic Aberrations in Mental Disorders are Linked to Diet and Gut Microbiome Alterations | Chapter 12 | Advanced Concepts in Medicine and Medical Research Vol. 10

Food and metabolism modify epigenetic codes to a degree histone methylation or acetylation and DNA methylation intervened by bioactive nutrients and gut microbial factors by way of influencing the gut–brain hinge, which adjust neuronal activity and behavior.This stage discusses epigenetic aberrations had connection with diet and gut microbiome alterations in major psychiatric afflictions such as schizophrenia, manic-depressive illness, and autism. Here, this study first argued modifications to the structure and makeup of gut microbiome and their duty in brain functional changes in weighty mental sicknesses. Afterwards, potential interactions with maternal diet, environmental determinants, nutrition, and gastrointestinal microbiome, and their acts in the pathogenesis of mental illnesses by way of epigenetic changes were discussed. This study still provided an overview of the friendship between the gut microbiome, oxidative stress, and inflammation moving epigenetic mechanisms. Furthermore, this chapter presented latent mechanisms which arbitrate the influence of gut microbiome, probiotics, and psychiatric drugs on insane health via microbiome-epigenetic modifications. Completely, it was concluded that disease pathogenesis is connected to changes in the microbiome structure/arrangement by perturbing the microbiome–gut-brain axle functions. Further research is needed to obtain better insights on unusually transmitted microbiomes on infant well-being, to mitigate the inceptions of neurodevelopmental diseases at early ages.

Author(s) Details:

Shabnam Nohesara,
Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.

Hamid Mostafavi Abdolmaleky,
Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA and Department of Surgery, Nutrition / Metabolism Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boson, MA, 02215, USA.

Sam Thiagalingam,
Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA and Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, MA, 02118, USA.

Please see the link here: https://stm.bookpi.org/ACMMR-V10/article/view/12837

A Therapeutic Application of Systematic Review with Meta-analysis: Epigenetic Analysis Tools and Cancer’s Therapy Assessment | Book Publisher International

 Epigenetics will produce a plethora of novel biomarkers to aid in the refinement of cancer therapies and patient drug response; they can be utilised as markers to predict clinical outcome and the likelihood of relapse after chemotherapies.

According to a Prisma flow chart, a total of 1302 articles were retrieved, 151 full-text articles were assessed for eligibility, and 47 studies with low to moderate quality were found to be eligible and involved in systematic review as a qualitative phase, while only 19 studies with moderate quality met the meta-analysis criteria, with a total of 6,086 patients from more than 25 countries.

Only two epigenetic alterations, DNA methylation and histone modifications, were employed to assess the response outcomes of cancer therapy, according to a comprehensive study. DNA methylation was discovered to be the most well-known epigenetic change, which was linked to either better or worse outcomes based on the connected gene, which might be oncogenes or tumour suppressor genes.

The epigenetic DNA methylation has a tendency to predict outcomes (HR= 0.603, CI= 0.462-0.788) in distinct cancer types treated with chemotherapeutic drugs, surgery, and radiotherapy, according to both fixed and random meta-analysis models. However, there were reports of substantial heterogeneity and publication bias. The reasons for heterogeneity were investigated using sub-groups analysis, and they appear to be linked to clinical and methodological variations among the studies.

The first grouping, oncogene methylation or DNA repair gene methylation, exhibited improved cancer patient outcome prediction (HR= 0.5, CI= 0.45-0.55), with minimal publication bias and heterogeneity (Q= 25.24, and I2 = 40.58 percent) among the studies. The second subgroup found that methylation of tumour suppressor genes was linked to poorer outcomes (HR= 2.07, CI= 1.77-2.43), with no heterogeneity (Q= 1.73, and I2 = 0.00) between studies.

Our findings revealed that methylation of the MGMT gene promoter was a strong outcomes predictor (HR=0.528, CI= 0.493-0.566) of cancer patients, particularly when alkylating chemotherapeutic agents were used with or without radiotherapy. Furthermore, the correlation of MGMT with overall survival revealed that methylation of the MGMT promoter was a good predictive biomarker of cancer therapies. These results had minimal heterogeneity (Q= 28.35, and I2= 43.57), and there was no evidence of publication bias.

The three sensitivity analysis techniques for MGMT-promoter methylation as a good predictive biomarker; statistical models, one study removal, and study design revealed that the pooled effect did not differ when the statistical models (fixed or random) of meta-analysis, or one study removal analysis, or study design change were changed.

Regarding the use of epigenetic tools in cancer therapy assessment, large articles with varied designs were dispersed over 13% of the global countries, representing around 6000 patients of low to moderate quality.

Due to clinical and methodological variability among the research, meta-analysis corroborated the systematic review findings regarding DNA-methylation as the best epigenetic tool with substantial heterogeneity and publication bias.

Finally, we conclude that MGMT gene methylation can be used as a predictive biomarker for cancer therapies and is associated with improved overall survival. These findings were not based on a single study and were not affected by changes in statistical models or study designs. Additionally, the unpublished or unretrieved studies in our review had no effect on the findings.

Author(S) Detalis

Hind Mohammed Osman Khalifa
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Omdurman Islamic University, P.O. Box 382, Omdurman, Sudan.

Aimun Abdelgaffar Elhassan Ahmed
Department of Pharmacology, Faculty of Pharmacy, P.O. Box 382, Omdurman Islamic University, Omdurman, Sudan and Department of Pharmacology, Faculty of Medicine, Al Baha University, P.O. Box 1988, KSA.

View Book:- https://stm.bookpi.org/ATASRMEATCTA/article/view/3734

Understanding the Molecular Mechanism Arsenic Cancer | Chapter 6 | Research Trends and Challenges in Medical Science Vol. 5

 Arsenic is a proven but enigmatic carcinogen. It produces human cancer although the mechanism is   unclear. It doesn’t induces point mutation. Therefore the general procedure of cancer promotion is missing here and epigenetic events has been mooted as an alternate pathway of arsenic induced carcinogenesis. Aberrant DNA methylation and histone modification has been classified and proven as the mechanism of arsenic induced carcinogenesis. Arsenic methylation and DNA methylation both the pathways are using same enzymes and methyl donor. Therefore, the role of arsenic metabolising gene and there polymorphisms in DNA methylation has been analysed and a positive association has been found. We have also analysed the degree of histone modifications and it’s role in arsenic induced cancer. Gene expression and association of mi RNA has been pointed out to explore the molecular mechanism of arsenic induced cancer. Although the scope is limited, this paper also lighten on the future therapeutics of arsenic induced cancer. This is a platform on which many of our future research can be based on, although it lack the power of discussion about nutritional aspects and it’s association with aberrant methylation and subsequent development of cancer.

Author (s) Details

Dr. Sarmishtha Chanda
Department of Physiology, West Bengal Education Service, West Bengal, India.

View Book:- https://bp.bookpi.org/index.php/bpi/catalog/book/264