keyword
https://read.qxmd.com/read/38460939/cancer-associated-polybromo-1-bromodomain-4-missense-variants-variably-impact-bromodomain-ligand-binding-and-cell-growth-suppression
#21
JOURNAL ARTICLE
Karina L Bursch, Christopher J Goetz, Guanming Jiao, Raymundo Nuñez, Michael D Olp, Alisha Dhiman, Mallika Khurana, Michael T Zimmermann, Raul A Urrutia, Emily C Dykhuizen, Brian C Smith
The Polybromo, BRG1-associated factors (PBAF) chromatin remodeling complex subunit Polybromo-1 (PBRM1) contains six bromodomains that recognize and bind acetylated lysine residues on histone tails and other nuclear proteins. PBRM1 bromodomains thus provide a link between epigenetic post-translational modifications and PBAF modulation of chromatin accessibility and transcription. As a putative tumor suppressor in several cancers, PBRM1 protein expression is often abrogated by truncations and deletions. However, ∼33% of PBRM1 mutations in cancer are missense and cluster within its bromodomains...
March 7, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38457193/-block-and-lock-viral-integration-sites-in-persons-with-drug-free-control-of-hiv-1-infection
#22
JOURNAL ARTICLE
Benjamin Bone, Mathias Lichterfeld
PURPOSE OF REVIEW: Elite controllers (ECs) and Posttreatment controllers (PTCs) represent a small subset of individuals who are capable of maintaining drug-free control of HIV plasma viral loads despite the persistence of a replication-competent viral reservoir. This review aims to curate recent experimental studies evaluating viral reservoirs that distinguish EC/PTC and may contribute to their ability to maintain undetectable viral loads in the absence of antiretroviral therapy. RECENT FINDINGS: Recent studies on ECs have demonstrated that integration sites of intact proviruses in EC/PTC are markedly biased towards heterochromatin regions; in contrast, intact proviruses in accessible and permissive chromatin were profoundly underrepresented...
February 29, 2024: Current Opinion in HIV and AIDS
https://read.qxmd.com/read/38451469/integration-of-demethylation-activated-dnazyme-with-a-single-quantum-dot-nanosensor-for-sensitive-detection-of-o-6-methylguanine-dna-methyltransferase-in-breast-tissues
#23
JOURNAL ARTICLE
Yun Han, Dong-Ling Li, Qian Han, Fei Ma, Chun-Yang Zhang
O6 -Methylguanine-DNA-methyltransferase (MGMT) is a demethylation protein that dynamically regulates the O6 -methylguanine modification (O6 MeG), and dysregulated MGMT is implicated in various malignant tumors. Herein, we integrate demethylation-activated DNAzyme with a single quantum dot nanosensor to sensitively detect MGMT in breast tissues. The presence of MGMT induces the demethylation of the O6 MeG-caged DNAzyme and the restoration of catalytic activity. The activated DNAzyme then specifically cleaves the ribonucleic acid site of hairpin DNA to expose toehold sequences...
March 7, 2024: Analytical Chemistry
https://read.qxmd.com/read/38450326/questionnaire-based-exposome-wide-association-studies-for-common-diseases-in-the-personalized-environment-and-genes-study
#24
JOURNAL ARTICLE
Dillon Lloyd, John S House, Farida S Akhtari, Charles P Schmitt, David C Fargo, Elizabeth H Scholl, Jason Phillips, Shail Choksi, Ruchir Shah, Janet E Hall, Alison A Motsinger-Reif
The exposome collectively refers to all exposures, beginning in utero and continuing throughout life, and comprises not only standard environmental exposures such as point source pollution and ozone levels but also exposures from diet, medication, lifestyle factors, stress, and occupation. The exposome interacts with individual genetic and epigenetic characteristics to affect human health and disease, but large-scale studies that characterize the exposome and its relationships with human disease are limited...
2024: Exposome
https://read.qxmd.com/read/38446993/plasma-proteomic-signature-predicts-myeloid-neoplasm-risk
#25
JOURNAL ARTICLE
Duc Tran, J Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C C Chan, Zilan Xin, Michael H Kramer, Armel L Batchi-Bouyou, Xiaoyu Zong, Matthew J Walter, Giulia E M Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T Oh, Daniel C Link, Ben Busby, Yin Cao, Kelly L Bolton
PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development. EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry...
March 6, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38434763/unraveling-the-role-of-m1-macrophage-and-cxcl9-in-predicting-immune-checkpoint-inhibitor-efficacy-through-multicohort-analysis-and-single-cell-rna-sequencing
#26
JOURNAL ARTICLE
Yunfang Yu, Haizhu Chen, Wenhao Ouyang, Jin Zeng, Hong Huang, Luhui Mao, Xueyuan Jia, Taihua Guan, Zehua Wang, Ruichong Lin, Zhenjun Huang, Hanqi Yin, Herui Yao, Kang Zhang
The exact function of M1 macrophages and CXCL9 in forecasting the effectiveness of immune checkpoint inhibitors (ICIs) is still not thoroughly investigated. We investigated the potential of M1 macrophage and C-X-C Motif Chemokine Ligand 9 (CXCL9) as predictive markers for ICI efficacy, employing a comprehensive approach integrating multicohort analysis and single-cell RNA sequencing. A significant correlation between high M1 macrophage and improved overall survival (OS) and objective response rate (ORR) was found...
March 2024: MedComm
https://read.qxmd.com/read/38427976/epigenetic-regulation-of-sex-dimorphism-in-cardiovascular-health
#27
JOURNAL ARTICLE
Charan Thej, Raj Kishore
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality, affecting people of all races, ages, and sexs. Substantial sex dimorphism exists in the prevalence, manifestation, and outcomes of cardiovascular diseases (CVD). Understanding the role of sex hormones as well as sex-hormone-independent epigenetic mechanisms could play a crucial role in developing effective and sex specific cardiovascular therapeutics. Existing research highlights significant disparities in sex hormones, epigenetic regulators, and gene expression related to cardiac health, emphasizing the need for a nuanced understanding of these variations between men and women...
March 1, 2024: Canadian Journal of Physiology and Pharmacology
https://read.qxmd.com/read/38426100/deciphering-the-fibrotic-process-mechanism-of-chronic-radiation-skin-injury-fibrosis
#28
REVIEW
Yiren Wang, Shouying Chen, Shuilan Bao, Li Yao, Zhongjian Wen, Lixia Xu, Xiaoman Chen, Shengmin Guo, Haowen Pang, Yun Zhou, Ping Zhou
This review explores the mechanisms of chronic radiation-induced skin injury fibrosis, focusing on the transition from acute radiation damage to a chronic fibrotic state. It reviewed the cellular and molecular responses of the skin to radiation, highlighting the role of myofibroblasts and the significant impact of Transforming Growth Factor-beta (TGF-β) in promoting fibroblast-to-myofibroblast transformation. The review delves into the epigenetic regulation of fibrotic gene expression, the contribution of extracellular matrix proteins to the fibrotic microenvironment, and the regulation of the immune system in the context of fibrosis...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38420827/recent-advancements-in-the-atopic-dermatitis-mechanism
#29
REVIEW
Maria Savva, Nikolaos G Papadopoulos, Stamatis Gregoriou, Spyridoula Katsarou, Niki Papapostolou, Michael Makris, Paraskevi Xepapadaki
Atopic dermatitis (AD) is a recurrent, chronic, inflammatory, itchy skin disorder that affects up to 20% of the pediatric population and 10% of the adult population worldwide. Onset typically occurs early in life, and although cardinal disease features are similar across all ages, different age groups and ethnicities present distinct clinical characteristics. The disease imposes a significant burden in all health-related quality of life domains, both in children and adults, and a substantial economic cost both at individual and national levels...
February 22, 2024: Frontiers in Bioscience (Landmark Edition)
https://read.qxmd.com/read/38413373/treatment-resistance-in-pancreatic-and-biliary-tract-cancer-molecular-and-clinical-pharmacology-perspectives
#30
REVIEW
Belén Toledo, Chiara Deiana, Fabio Scianò, Giovanni Brandi, Juan Antonio Marchal, Macarena Perán, Elisa Giovannetti
INTRODUCTION: Treatment resistance poses a significant obstacle in oncology, especially in biliary tract cancer (BTC) and pancreatic cancer (PC). Current therapeutic options include chemotherapy, targeted therapy, and immunotherapy. Resistance to these treatments may arise due to diverse molecular mechanisms, such as genetic and epigenetic modifications, altered drug metabolism and efflux, and changes in the tumor microenvironment. Identifying and overcoming these mechanisms is a major focus of research: strategies being explored include combination therapies, modulation of the tumor microenvironment, and personalized approaches...
February 27, 2024: Expert Review of Clinical Pharmacology
https://read.qxmd.com/read/38408508/genome-wide-association-study-and-mendelian-randomization-analyses-provide-insights-into-the-causes-of-early-onset-colorectal-cancer
#31
JOURNAL ARTICLE
R S Laskar, C Qu, J R Huyghe, T Harrison, R B Hayes, Y Cao, P T Campbell, R Steinfelder, F R Talukdar, H Brenner, S Ogino, S Brendt, D T Bishop, D D Buchanan, A T Chan, M Cotterchio, S B Gruber, A Gsur, B van Guelpen, M A Jenkins, T O Keku, B M Lynch, L Le Marchand, R M Martin, K McCarthy, V Moreno, R Pearlman, M Song, K K Tsilidis, P Vodička, M O Woods, K Wu, L Hsu, M J Gunter, U Peters, N Murphy
BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. Colorectal cancer (CRC) has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC...
February 24, 2024: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://read.qxmd.com/read/38398194/cholangiocarcinoma-recent-advances-in-molecular-pathobiology-and-therapeutic-approaches
#32
REVIEW
Divya Khosla, Shagun Misra, Pek Lim Chu, Peiyong Guan, Ritambhra Nada, Rajesh Gupta, Khwanta Kaewnarin, Tun Kiat Ko, Hong Lee Heng, Vijay Kumar Srinivasalu, Rakesh Kapoor, Deepika Singh, Poramate Klanrit, Somponnat Sampattavanich, Jing Tan, Sarinya Kongpetch, Apinya Jusakul, Bin Tean Teh, Jason Yongsheng Chan, Jing Han Hong
Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e...
February 16, 2024: Cancers
https://read.qxmd.com/read/38398001/genetic-and-epigenetic-aspects-of-type-1-diabetes-mellitus-modern-view-on-the-problem
#33
REVIEW
Ildar Minniakhmetov, Bulat Yalaev, Rita Khusainova, Ekaterina Bondarenko, Galina Melnichenko, Ivan Dedov, Natalia Mokrysheva
Omics technologies accumulated an enormous amount of data that advanced knowledge about the molecular pathogenesis of type 1 diabetes mellitus and identified a number of fundamental problems focused on the transition to personalized diabetology in the future. Among them, the most significant are the following: (1) clinical and genetic heterogeneity of type 1 diabetes mellitus; (2) the prognostic significance of DNA markers beyond the HLA genes; (3) assessment of the contribution of a large number of DNA markers to the polygenic risk of disease progress; (4) the existence of ethnic population differences in the distribution of frequencies of risk alleles and genotypes; (5) the infancy of epigenetic research into type 1 diabetes mellitus...
February 8, 2024: Biomedicines
https://read.qxmd.com/read/38385496/dietary-plant-metabolites-induced-epigenetic-modification-as-a-novel-strategy-for-the-management-of-prostate-cancer
#34
JOURNAL ARTICLE
Vaibhav Singh, Ekta Shirbhate, Rakesh Kore, Aditya Mishra, Varsha Johariya, Ravichandran Veerasamy, Amit K Tiwari, Harish Rajak
Prostate cancer is a widespread malignancy among men, with a substantial global impact on morbidity and mortality. Despite advances in conventional therapies, the need for innovative and less toxic treatments remains a priority. Emerging evidence suggests that dietary plant metabolites possess epigenetic-modifying properties, making them attractive candidates for prostate cancer treatment. The present work reviews the epigenetic effects of dietary plant metabolites in the context of prostate cancer therapy...
February 21, 2024: Mini Reviews in Medicinal Chemistry
https://read.qxmd.com/read/38379272/epigenetics-as-a-key-factor-in-prostate-cancer
#35
REVIEW
Kadriia Enikeeva, Guzel Rafikova, Yuliya Sharifyanova, Diana Mulyukova, Alexandr Vanzin, Valentin Pavlov
Nowadays, prostate cancer is one of the most common forms of malignant neoplasms in men all over the world. Against the background of increasing incidence, there is a high mortality rate from prostate cancer, which is associated with an inadequate treatment strategy. Such a high prevalence of prostate cancer requires the development of methods that can ensure early detection of the disease, improve the effectiveness of treatment, and predict the therapeutic effect. Under these circumstances, it becomes crucial to focus on the development of effective diagnostic and therapeutic approaches...
February 20, 2024: Advanced biology
https://read.qxmd.com/read/38371024/clinically-actionable-topical-strategies-for-addressing-the-hallmarks-of-skin-aging-a-primer-for-aesthetic-medicine-practitioners
#36
REVIEW
Piercarlo Minoretti, Enzo Emanuele
In this narrative review, we sought to provide a comprehensive overview of the mechanisms underlying cutaneous senescence, framed by the twelve traditional hallmarks of aging. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, impaired macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. We also examined how topical interventions targeting these hallmarks can be integrated with conventional aesthetic medicine techniques to enhance skin rejuvenation...
January 2024: Curēus
https://read.qxmd.com/read/38364552/molecular-crosstalk-between-polyphenols-and-gut-microbiota-in-cancer-prevention
#37
REVIEW
Falak Zeb, Huma Naqeeb, Tareq Osaili, MoezAllslam Ezzat Faris, Leila Cheikh Ismail, Reyad Shakir Obaid, Farah Naja, Hadia Radwan, Hayder Hasan, Mona Hashim, Sharifa AlBlooshi, Iftikhar Alam
A growing body of evidence suggests that cancer remains a significant global health challenge, necessitating the development of novel therapeutic approaches. In recent years, the molecular crosstalk between polyphenols and gut microbiota has emerged as a promising pathway for cancer prevention. Polyphenols, abundant in many plant-based foods, possess diverse bioactive properties, including antioxidant, anti-inflammatory, and anticancer activities. The gut microbiota, a complex microbial community residing in the gastrointestinal tract, plays a crucial role in a host's health and disease risks...
January 27, 2024: Nutrition Research
https://read.qxmd.com/read/38355298/of-mice-and-men-the-inter-individual-variability-of-the-brain-s-response-to-drugs
#38
JOURNAL ARTICLE
Wolfgang Löscher
Biological variation is ubiquitous in nature. Despite highly standardized breeding and husbandry under controlled environmental conditions, phenotypic diversity exists in laboratory mice and rats just as it does in humans. The resulting inter-individual variability affects various characteristics of animal disease models, including the responsiveness to drugs. Thus, the common practice of averaging data within an experimental group can lead to misinterpretations in neuroscience and other research fields. In this commentary, the impact of inter-individual variation in drug responsiveness is illustrated by examples from the testing of antiseizure medications in rodent temporal lobe epilepsy models...
February 2024: ENeuro
https://read.qxmd.com/read/38350182/optimizing-therapeutic-targets-for-breast-cancer-using-boolean-network-models
#39
JOURNAL ARTICLE
Domenico Sgariglia, Flavia Raquel Gonçalves Carneiro, Luis Alfredo Vidal de Carvalho, Carlos Eduardo Pedreira, Nicolas Carels, Fabricio Alves Barbosa da Silva
Studying gene regulatory networks associated with cancer provides valuable insights for therapeutic purposes, given that cancer is fundamentally a genetic disease. However, as the number of genes in the system increases, the complexity arising from the interconnections between network components grows exponentially. In this study, using Boolean logic to adjust the existing relationships between network components has facilitated simplifying the modeling process, enabling the generation of attractors that represent cell phenotypes based on breast cancer RNA-seq data...
February 7, 2024: Computational Biology and Chemistry
https://read.qxmd.com/read/38345160/flow-cytometry-of-dnmt1-as-a-biomarker-of-hypomethylating-therapies
#40
JOURNAL ARTICLE
Philip G Woost, Basem M William, Brenda W Cooper, Masumi Ueda Oshima, Folashade Otegbeye, Marcos J De Lima, David Wald, Reda Z Mahfouz, Yogen Saunthararajah, Tammy Stefan, James W Jacobberger
The 5-azacytidine (AZA) and decitabine (DEC) are noncytotoxic, differentiation-inducing therapies approved for treatment of myelodysplastic syndrome, acute myeloid leukemias (AML), and under evaluation as maintenance therapy for AML postallogeneic hematopoietic stem cell transplant and to treat hemoglobinapathies. Malignant cell cytoreduction is thought to occur by S-phase specific depletion of the key epigenetic regulator, DNA methyltransferase 1 (DNMT1) that, in the case of cancers, thereby releases terminal-differentiation programs...
February 12, 2024: Cytometry. Part B, Clinical Cytometry
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