Результаты поиска

Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.

The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabe

Совпадение в полном тексте источника
… Only mono and demethylation have been described for arginine residues. While methylation of DNA is generally associated with gene silencing, histone methylation on lysine residue, catalysed by histone methyl transferase HMT, can lead both to activation and inhibition (Miller and Grant 2013 ). … GLP-1RAs showed in human aortic endothelial cells exposed to high glucose and in diabetic patients to prevent glucose-induced DNA demethylation of NF-kB promoter by reducing TET2 binding. …

Epigenetic Therapies for Acute Myeloid Leukemia and Their Immune-Related Effects.

Over the past decades, our molecular understanding of acute myeloid leukemia (AML) pathogenesis dramatically increased, thanks also to the advent of next-generation sequencing (NGS) technologies. Many of these findings, however, have not yet translated into new prognostic markers or rationales for treatments. We now know that AML is a highly heterogeneous disease characterized by a very low mutational burden. Interestingly, the few mutations identified mainly reside in epigenetic regulators, which shape and define leukemic cell identity. In the light of these discoveries and given the increasi

DNA Damaging Drugs

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… Pharmacokinetics After administration, pentamethylmelamine is extensively demethylated by hepatic mixed-function oxidases. … Methylmelamines release the weakly alkylating formaldehyde upon demethylation . Methylated melamines are extensively demethylated by hepatic mixed-function oxidases. Their anti-tumor activity decreases with a decreasing number of methyl groups . …

The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies.

Immunotherapy has emerged as a preeminent force in the domain of cancer therapeutics and achieved remarkable breakthroughs. Nevertheless, the high resistance has become the most substantial impediment restricting its clinical efficacy. Beta-2 microglobulin (B2M), the light chain of major histocompatibility complex (MHC) class I, plays an indispensable part by presenting tumor antigens to cytotoxic T lymphocytes (CTLs) for exerting anti-tumor effects. Accumulating evidence indicates that B2M mutation/defect is one of the key mechanisms underlying tumor immunotherapy resistance. Therefore, eluci

Совпадение в полном тексте источника
… On the contrary, the Kobayashi team utilized a gene-specific system based on CRISPR/Cas9 technology, designated as TRED-I (Targeted reactivation and demethylation for MHC-I), to accomplish targeted demethylation of the NLRC5 promoter, induce an augmentation in NLRC5 expression, thereby upregulating MHC-I … Targeted demethylation and activation of NLRC5 augment cancer immunogenicity through MHC class I. Proc Natl Acad Sci U.S.A. (2024) 121:e2310821121. doi: 10.1073/pnas.2310821121 38. Burr ML, Sparbier CE, Chan KL, Chan YC, Kersbergen A, Lam EYN, et al. …

Research progress on N6-methyladenosine and non-coding RNA in multiple myeloma.

N6-methyladenosine (m6A) and non-coding RNA (ncRNA) play important roles in the occurrence, development, and prognosis of multiple myeloma (MM). They not only affect stemness, growth, and apoptosis of MM cells but also intervene in MM proliferation, migration, invasion, and even drug resistance. It is also a prognostic factor for poor MM survival. Therefore, in-depth research on the mechanisms of m6A and ncRNA in MM significant for diagnosis, treatment, and prognosis of MM.

Совпадение в полном тексте источника
… Alkbh5 promotes multiple myeloma tumorigenicity through inducing m(6)a-demethylation of sav1 mrna and myeloma stem cell phenotype. Int J Biol Sci. 2022;18(6):2235–48. 10.7150/ijbs.64943. 35414790 10.7150/ijbs.64943 PMC8990482 28. … Alkhb5-demethylated lncrna snhg15 promotes myeloma tumorigenicity by increasing chromatin accessibility and recruiting h3k36me3 modifier setd2. Am J Physiol Cell Physiol. 2024;326(3):C684–97. 10.1152/ajpcell.00348.2023. 38145297 10.1152/ajpcell.00348.2023 PMC11193452 …

Exploring the impact of m6A modification on immune diseases: mechanisms and therapeutic implication.

N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and system

Полнотрансформатная ретиноидальная кислота в гематологическое расстройство: не только острая промиелоцитическая лейкемия.

Всетранс-ретиноиновая кислота (ATRA) играет определенную роль в развитии тканей, нейронной функции, воспроизводстве, зрение, росте и дифференциации клеток, иммунитете от опухоли и апоптозе. АТРА может действовать, вызывая автофагическую сигнализацию, ангиогенез, клеточную дифференциацию, апоптоз и иммунную функцию. В крови ATRA впервые с большим успехом использовалась в острой промиелоцитической лейкемии (APL), где ATRA дифференцировала клетки лейкемии на зрелые гранулоциты. АТРА может играть определенную роль не только в ППН, но и в других гематоологических заболеваниях, таких, как иммунная т

The Hedgehog-GLI pathway in embryonic development and cancer: implications for pulmonary oncology therapy.

Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies. Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas. In

Совпадение в полном тексте источника
… of the Hh pathway: implications for pulmonary oncology therapeutics Epigenetic profile of the Hh pathway Genomic DNA methylation analysis is based on the detection and quantification of the covalent addition of methyl groups to the fifth position of a cytosine base (5-methyl-cytosine “5mC”) or of demethylation … 0537-9 18060563 10.1007/s00441-007-0537-9 9 Montavon T Duboule D Chromatin organization and global regulation of Hox gene clusters Philos Trans R Soc B Biol Sci 2013 368 20120367 20120367 https://doi.org/10.1098/rstb.2012.0367 10.1098/rstb.2012.0367 PMC3682730 23650639 10 Dean W DNA methylation and demethylation …

Человеческие эндогенные ретровирусы как новые терапевтические цели в нейродегенеративных расстройствах.

Человеческие эндогенные ретровирусы составляют приблизительно 8% генома человека и служат фрагментами древних антиретровирусных инфекций. Хотя они, как правило, удерживаются в замалчиваемом состоянии с помощью надежных эпигенетических механизмов, конкретные группы HERV, в частности HERV-W и HERV-K, могут депрессировать в конкретных патологических условиях, что способствует инициированию и продвижению нейро-воспалительных и нейродегенеративных процессов. Доклинические исследования и клинические испытания, такие, как исследования моноклонных антител, показывают, что прямая ориентация на эти элем

Совпадение в полном тексте источника
… Additionally, demethylating agents such as DNA methyltransferase (DNMT) inhibitors have gained considerable attention due to their capability to modulate DNA methylation patterns directly [ 100 ]. … However, this therapeutic strategy must be carefully tailored to achieve specificity, as global demethylation may inappropriately activate other genomic elements or disrupt normal gene regulation. …

Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induc

Совпадение в полном тексте источника
… Moreover, other studies have shown that treatment with a potent activator such as TNF-α results in demethylation of CpG islands within the 5′ LTR [ 69 , 86 , 87 ]. … Early studies demonstrated that azacitidine treatment resulted in demethylation of the HIV-1 LTR and reactivation in a T cell line containing an HIV-1 LTR reporter construct [ 62 , 63 ] and in ACH2 cells [ 68 ]. …

Impact of Alterations in Homocysteine, Asymmetric Dimethylarginine and Vitamins-Related Pathways in Some Neurodegenerative Diseases: A Narrative Review.

Hyperhomocysteinemia (HHcy) influences the development and progression of neurodegenerative disorders in different ways. Homocysteine (Hcy) metabolism is related to that of asymmetric dimethylarginine (ADMA) and group B vitamins. The breakdown of the pathway involving nitric oxide (NO) and ADMA can be considered one of the causes of endothelial alteration that represents a crucial step in the development of several neurodegenerative disorders. Deficiencies of vitamins other than group B ones, such as D and A, have also been associated with central nervous system disorders. The aim of this narr

Совпадение в полном тексте источника
… Based on evidence about methylation/demethylation, SAM is considered to be the main donor of methyl groups in numerous metabolic processes, leading to the formation of methyl derivatives. … Epigenetic modifications mediate AD onset and progression; in particular, the Presenilin 1 ( PS1 ) gene is a specific locus of demethylation in AD patients. …

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progress

Совпадение в полном тексте источника
… Emerging evidence revealed that curcumin suppresses STAT3 by reactivating the receptor activator of NF-κB (RANK) via demethylation through epigenetic modification in human glioblastoma cells [ 116 ]. … Genistein-provoked demethylation of CHD5 promoter was thought to be associated with DNA-methyltransferase 3 beta suppression [ 159 ]. In addition, genistein also improves the effect of chemotherapeutic drugs in brain tumor management. …

The Impact and Safety of GLP-1 Agents and Breast Cancer.

IntroductionObesity and breast cancer rates are increasing globally, with obesity prevalence more than doubling since 1990. By 2022, 44% of women were overweight, and 18% were obese. Breast cancer remains the most common malignancy among women, with 2.2 million new cases in 2020. A significant proportion of breast cancer patients are overweight or obese at diagnosis, which is associated with higher recurrence and mortality rates. Recently, GLP-1 receptor agonists (GLP-1 RAs) have emerged as remarkably effective weight loss drugs. Understanding the relationship between obesity, breast cancer, a

Совпадение в полном тексте источника
… Similar to the results in the breast cancer cell lines, the liraglutide treatment produced significant demethylation in CDH1 and ADAM33 promoter regions. Specifically, in the ADAM33 promoter region, there was a significant reduction in the methylation profile of CpG islands close to 55%. … These results prove that liraglutide treatment reached the tumors and induced demethylation. This increase in gene expression may lead to potentially improved tumor prognosis [ 86 ]. …

Current Advances of Nanomedicines Delivering Arsenic Trioxide for Enhanced Tumor Therapy.

Arsenic trioxide (ATO) is one of the first-line chemotherapeutic drugs for acute promyelocytic leukemia. Its anti-cancer activities against various human neoplastic diseases have been extensively studied. However, the clinical use of ATO for solid tumors is limited, and these limitations are because of severe systemic toxicity, low bioavailability, and quick renal elimination before it reaches the target site. Although without much success, several efforts have been made to boost ATO bioavailability toward solid tumors without raising its dose. It has been found that nanomedicines have various

Совпадение в полном тексте источника
… Hassani S et al. suggested that the demethylation of cyclin genes by ATO such as CCND1 and CCNE1 accelerates G1 and S transition into the G2/M cell cycle arrest [ 49 ]. Many reports have shown that cancer stem cells (CSCs) play a critical role in sustaining the malignant phenotype. … Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB 4 ) Ann. Hematol. 2018 97 83 93 10.1007/s00277-017-3163-y 29159499 50. Yang Z.F. Ngai P. Ho D.W. Yu W.C. Ng M.N. …

Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology.

Oleocanthal (OC), a secoiridoid phenolic compound exclusive to extra virgin olive oil (EVOO), has emerged as a promising nutraceutical with multifaceted anti-cancer properties. Despite its well-characterized anti-inflammatory and antioxidant effects, the mechanistic breadth and translational potential of OC in oncology remain underexplored and fragmented across the literature. This comprehensive review synthesizes and critically analyzes recent advances in the molecular, pharmacological, and translational landscape of OC's anti-cancer activities, providing an integrative framework to bridge pr

Совпадение в полном тексте источника
… Similarly, the demethylation of repressive histone marks such as H3K9me2/3 and H3K27me3 leads to chromatin de-repression and the activation of oncogenic gene expression programs. … These modifications are mechanistically linked to OC’s anti-inflammatory properties, as H3K9 demethylation typically promotes pro-inflammatory gene activation, while H3K27 demethylation is associated with chromatin relaxation and the transcriptional activation of immune response genes. …

Cobalamin deficiency, hyperhomocysteinemia, and dementia.

IntroductionAlthough consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1) Which patients should be tested? (2) What test should be ordered? (3) How are inferences made from such testing? (4) In addition to serum B12, should other tests be ordered? (5) Is B12 deficiency compatible with dementia of the Alzheimer's type? (6) What is to be expected from treatment? (7) How is B12 deficiency treated?MethodsOn January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hype

Совпадение в полном тексте источника
… Methyl groups produced by AdoMet demethylation to AdoHcy are used for nucleic acid, protein, lipid, and neurotransmitter biosynthesis. Cysteine is a nonessential amino acid used in the biosynthesis of proteins, glutathione, coenzyme A, taurine, and inorganic sulfur. … SAM demethylation to SAH serves as a methyl group donor for the biosynthesis of nucleic acids, proteins, phospholipids, and catecholamines and the metabolism of drugs and toxins. …

Targeting the epigenome to treat neurodegenerative diseases or delay their onset: a perspective.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… For example, it was shown that decitabine exacerbates neurotoxicity and upregulates PD-related genes in cultured dopaminergic neurons, including demethylation of the SNCA gene coding for α-synuclein (Wang et al., 2013). …

Polyphenols bind G4-Quadruplex structures and act as epigenetic modifiers with anti-cancer effects.

G4-quadruplexes (G4s) are non-canonical structures of nucleic acids that develop in guanine rich regions of DNA and RNA. Due to their presence in oncogenic promoters and telomeres, G4s represent attractive targets in anticancer drug designs. G4s have also been the subject of recent research regarding their role as epigenetic modulators, supporting their participation in epigenetic processes that control gene expression. The development of small compounds that preferentially target G4s have led to a better understanding of how G4s control these mechanisms. Natural products have greatly contribu

Совпадение в полном тексте источника
… Tumor cells are characterized by global DNA demethylation and local hypermethylation (Kisseljova and Kisseljov, 2005[ 87 ]). … DNA Demethylation and Carcinogenesis. Biochemistry (Moscow) 2005;70:743–52. doi: 10.1007/s10541-005-0179-z. 88. Kjær TN, Ornstrup MJ, Poulsen MM, Jørgensen JOL, Hougaard DM, Cohen AS, et al. …

Ось NSDHL/c-Myc/PKM2 ведет гликолитическое перепрограммирование и рост опухоли в множестве миелом.

Множественная миелома (ММ) остается в основном неизлечимой из-за ее сложной биологии и частого рецидива заболеваний. Перепрограммирование метаболических программ все чаще признается в качестве одного из важнейших факторов развития ММ. Зависящий от NAD (P) стероид дегидрогеназный белок (NSDHL) был выделен в качестве неблагоприятного прогностического гена, связанного с метаболизмом, в плазменной клеточной миеломе, но его функциональное значение и метаболическая роль в MM остаются неясными. Для оценки выражения НКПЧС и его клинической значимости были проанализированы общедоступные наборы данных M

Совпадение в полном тексте источника
… NAD (P)-dependent steroid dehydrogenase-like protein (NSDHL) is an enzyme involved in post-squalene cholesterol biosynthesis, where it participates in the C4-demethylation process during the conversion of lanosterol-derived sterol intermediates to cholesterol [ 8 ]. … Targeting C4-Demethylating Genes in the Cholesterol Pathway Sensitizes Cancer Cells to EGF Receptor Inhibitors via Increased EGF Receptor Degradation. Cancer Discov. 2013;3:96–111. doi: 10.1158/2159-8290.Cd-12-0031. 13. Huang H.-Y., Wang Y., Wang W.-D., Wei X.-L., Gale R.P., Li J.-Y., Zhang Q. …

The next new target in leukemia: The embryonic stem cell gene SALL4.

The embryonic stem (ES) cell gene SALL4 has recently been identified as a new target for cancer therapy, including leukemia. SALL4 is expressed in ES cells and during embryonic development, but is absent in most adult tissues. It is, however, aberrantly expressed in various solid tumors and hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Aberrant expression of SALL4 is frequently associated with a more aggressive cancer phenotype, which includes high-risk MDS and its progression to AML. SALL4 contributes to leukemogenesis through multiple path

Совпадение в полном тексте источника
… In breast cancer cells, STAT3 has been shown to be an upstream transcriptional activator of SALL4. 44 The mechanism underlying aberrant SALL4 expression in leukemia is not known although recent studies have suggested DNA demethylation as one possibility. 25 In a study using B-ALL cell lines and primary … Furthermore, treatment of low SALL4-expressing B-ALL cell lines with a DNA methylation inhibitor led to demethylation of the SALL4 CpG region and increased SALL4 expression. …