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Concentration-dependent effect of delta-9-tetrahydrocannabinol on epigenetic DNA modifiers in human peripheral blood mononuclear cells.

Cannabis is among the most used illicit substances in the world, and approximately 10% of regular cannabis users are estimated to be suscept … ions of THC may affect the expression of genes critical for the development of CUD through aberrant demethylation.

Enhanced neurotoxic effects following co-administration of methamphetamine and ethanol in rats: Insights from integrated analysis of behavior, pharmacokinetics, and metabolomics.

Methamphetamine (MA) is a psychostimulant with high potential for abuse and neurotoxicity, and overdose or concurrent use with ethanol (EtOH … d total clearance. Notably, EtOH co-administration reduced the hydroxylation of MA and enhanced its demethylation, potentially contributing to elevated toxicity and addictive potential. Time-course metabolic profiling of amino acids and polyamines showed that EtOH-induced potentiation of stereotypic behaviors correlated with a significant increase in plasma spe …

KDM2A demethylase: A versatile epigenetic regulator in development, cancer, and therapeutic horizons.

Lysine demethylase 2A (KDM2A), a crucial member of the histone demethylase family, plays a vital role in epigenetic regulation by modifying histone methylation and the chromatin structure. It regulates key cellular activities, including development, differentiation, and metabolism, by controlling gene expression and transcriptional silencing, and maintaining genomic stability through the demethylation of histone H3 at lysine 36 (H3K36). In addition to its canonical enzymatic role, KDM2A is involved in diverse biological processes, together with embryonic development, stem cell maintenance, DNA…

Лизин деметилаза 6 (KDM6): перспективная терапевтическая цель в области аутоиммунных расстройств и рака.

Эпигенетическая динамика, которая влияет на выражения генов независимо от изменений последовательности ДНК, играет ключевую роль в регулировании структуры хроматина и транскрипции. Среди этих модификаций подсемейство подметила 6 (KDM6) с помощью динамического метилирования и деметилирования гистона 3 лизины 27 (H3K27me2/3) являются ключевыми регуляторами как физиологических, так и патологических процессов. В иммунных клетках KDM6A и KDM6B совершенствуют транскрипцию про- и антивоспалительных генов, оказывая влияние на дифференциацию, поляризацию и активацию в моноцитах, макрофагах, дендритных

Совпадение в аннотации оригинала
Epigenetic dynamics, which influence gene expressions independent of DNA sequence alterations, play a pivotal role in regulating chromatin structure and transcription. Among these modifications, the dynamic methylation and demethylation of histone 3 lysine 27 (H3K27me2/3) by the Lysine Demethylase 6 (KDM6) subfamily are pivotal regulators of both physiologic…

Comparative Fitness of Monilinia fructicola Isolates with Multiple Fungicide-Resistant Phenotypes.

This study characterized 52 isolates of Monilinia fructicola from peach and nectarine orchards for their multiresistance patterns to thiophanate-methyl (TF), tebuconazole (TEB), and azoxystrobin (AZO) using in vitro sensitivity assays and molecular analysis. The radial growth of M. fructicola isolates was measured on media amended with a single discriminatory dose of 1 μg/ml for TF and AZO and 0.3 μg/ml for TEB. Cyt b, CYP51, and β-tubulin were tested for point mutations that confer resistance to quinone outside inhibitors (QoIs), demethylation inhibitors (DMIs), and methyl benzimidazole carba…

Wu Mei Wan suppresses colorectal cancer stemness by regulating Sox9 expression via JAK2/STAT3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Wu Mei Wan (WMW) is a traditional Chinese herbal formula with a long-standing history in Chinese medicine, v … xpression through the JAK2/STAT3 signaling pathway. Additionally, the regulation of methylation and demethylation mediated by TET1 and DNMT3a expression was directly associated with the JAK2/STAT3 pathway's modulation of Sox9 expression. In vivo, WMW treatment attenuated CRC progression and metastasis with minimal toxicity. CONCLUSION: These findings suggest t …

Severe caffeine poisoning with mexiletine successfully treated by extracorporeal methods.

A 20-year-old woman was brought to the hospital in an ambulance after ingesting 18 g of caffeine and 3500 mg of mexiletine 80 min earlier. O … has been reported that mexiletine may reduce the clearance of caffeine probably via inhibition of N-demethylation. In this case, the endogenous clearance of caffeine, calculated from blood concentrations, was considerably lower than estimated. If HD had not been performed, it may have taken longer to wean off the VA-ECMO because of reduced caffeine clearance in …

ALOX15-Driven Ferroptosis: The key target in Dihydrotanshinone I's epigenetic Battle in hepatic stellate cells against liver fibrosis.

BACKGROUND: It is known that ferroptosis promotes hepatic stellate cells (HSCs) inactivation. Arachidonate 15-Lipoxygenase (ALOX15), a ferro … CONCLUSION: DHI upregulates EGR1 level, leading to decreased DNMT1 expression and increased ALOX15 demethylation, thereby promoting HSC ferroptosis and inactivation.

CircMAPK1 induces cell pyroptosis in sepsis-induced lung injury by mediating KDM2B mRNA decay to epigenetically regulate WNK1.

BACKGROUND: Macrophage pyroptosis is a pivotal inflammatory mechanism in sepsis-induced lung injury, however, the underlying mechanisms rema … stically, loss of circMAPK1 enhanced the association between KDM2B and WNK1 promoter to promote the demethylation of WNK1 and increase its expression. CircMAPK1 facilitated KDM2B mRNA decay by recruiting UPF1. Functional experiments showed that silencing of KDM2B or WNK1 counteracted circMAPK1 knockdown-suppressed macrophage pyroptosis. In addition, silencing o …

Comparative profiling of the absorbed compounds and metabolites, and pharmacokinetic studies of Danshen-Chuanxiong herb pair in rat plasma and brain using liquid chromatography-tandem mass spectrometry.

Danshen-Chuanxiong (DS-CX) was a classic herb pair commonly used to treat ischemic stroke. Nevertheless, the metabolic conversion and pharma … major metabolic pathways were hydroxylation, methylation, deoxidation, dehydration, hydrogenation, demethylation, hydrolysis, decarboxylation and glucuronidation binding reactions. According to the results of metabolites profiling, sixteen active compounds (8 phenolic acids, 5 phthalides and 3 tanshinones) were selected as markers for further comparative pharm …

Epilimnetic oligotrophication increases contribution of oxic methane production to atmospheric methane flux from stratified lakes.

Although considerable attention has been paid to the effects of eutrophication on aquatic methane (CH4) emissions to the atmosphere, the eco … solved 13C-CH4, the potential substrates for OMP, and the phnJ/phnD genes associated with microbial demethylation of organic phosphorus compounds were analyzed. Our results indicate that CH4 accumulation was maximal in the surface mixed layer (SML, i.e., Epilimnion) during lake stratification, and ∼ 86 % of the total CH4 flux to the atmosphere was due to OMP. D …

Hydin as the Candidate Master Sex Determination Gene in Channel Catfish (Ictalurus punctatus) and Its Epigenetic Regulation.

Sex determination is a fascinating area of research. To date, more than 20 master sex determination (SD) genes have been reported from verte … em of channel catfish. Functional analysis using a methylation blocker, 5-aza-dC, demonstrated that demethylation, especially within the SDR, is accompanied with increased expression of hydin, which led to sex reversal of genetic females into phenotypic males. These evidences support the candidacy of hydin as a master SD gene in channel catfish. Future knockout …

The characteristic and bio-accessibility evaluation of mercury species in various kinds of seafood collected from Fujian of China for mercury risk assessment.

Seafood consumption is the major source of total Hg (tHg) and methyl mercury (MeHg) for humans. Lack of broad-representative bio-accessibili … Hg2+ during gastrointestinal digestion, which reduced the toxicity of mercury in seafood. The mean demethylation rate of MeHg varied as follows: seaweeds (⁓62.1 %) > shellfishes/shrimps (⁓19.7 %) > fishes (⁓9.2 %). The mean bio-accessibility of Hg2+ and tHg varied as follows: seaweeds (⁓97.7 % and ⁓90.1 %) > shellfishes/shrimps (⁓65.1 % and ⁓67.9 %) ≈ fishes ( …

Targeted CRISPR activation is functional in engineered human pluripotent stem cells but undergoes silencing after differentiation into cardiomyocytes and endothelium.

Human induced pluripotent stem cells (hiPSCs) offer opportunities to study human biology where primary cell types are limited. CRISPR techno … all loci and with all promoters. Promoter DNA was hypermethylated in CRISPRa-engineered lines, and demethylation with 5-azacytidine enhanced dCas9-VPR gene expression. In summary, the dCas9-VPR cDNA is readily expressed from multiple loci during pluripotency but induces silencing in a locus- and promoter-independent manner during differentiation to mesoderm de …

Severe induction of aberrant DNA methylation by nodular gastritis in adults.

BACKGROUND: Nodular gastritis (NG) is characterized by marked antral lymphoid follicle formation, and is a strong risk factor for diffuse-ty … tion, such as CXCL13/CXCR5 and CXCL12/CXCR4, had higher expression in NG, and genes involved in DNA demethylation TET2 and IDH1, had only half the expression in NG. CONCLUSIONS: Severe aberrant methylation, involving multiple tumor-suppressor genes, was induced in the gastric antrum and body of patients with NG, in accordance with their high gastric cancer ris …

Deucravacitinib is an allosteric TYK2 protein kinase inhibitor FDA-approved for the treatment of psoriasis.

Psoriasis is a heterogeneous, inflammatory, autoimmune skin disease that affects up to 2% of the world's population. There are many treatmen … c and other inflammatory diseases. The use of deuterium in the trimethylamide decreases the rate of demethylation and slows the production of a metabolite that is active against a variety of targets in addition to TYK2. A second unique aspect in the development of deucravacitinib is the targeting of a pseudokinase domain. Deucravacitinib is rather specific for …

Two patients with KDM3B variants and new presentations of Diets-Jongmans syndrome.

KDM3B is located on chromosome 5q31 and encodes KDM3B, which is involved in histone demethylation and epigenetic regulation. Pathogenic KDM3B variants cause a dominantly inherited disorder presenting with intellectual disability (ID), short stature, and facial dysmorphism, named Diets-Jongmans syndrome. We describe two patients with KDM3B variants presenting with Diets-Jongmans syndrome. Genetic testing was performed because of the clinical data and a lack of a clear diagnosis in both patients. Candidate variants were verified by Sanger sequencing. After KDM3B variants were detected, in silico…

Epigenome-wide DNA methylation analysis of myasthenia gravis.

Myasthenia gravis (MG) is a common neuromuscular junction disorder and autoimmune disease mediated by several antibodies. Several studies ha … thylation positions. Subsequently, C2C12 and HT22 cell lines (derived from mouse) were treated with demethylation drugs. Transcribed mRNA of the screened differential genes was detected using quantitative real-time PCR. The control and MG group were compared, and two key probe positions were selected. The corresponding genes were CAMK1D and CREB5 (P < 0.05). Si …

Elimination of tetracyclines in seawater by laccase-mediator system.

Long-term exposure of antibiotics at low level leads to the accumulation of antibiotics in environmental media and organisms, inducing the f … ophobic interaction. TCs were degraded into small molecular products through a series of reactions: demethylation, deamination, deamidation, dehydration, hydroxylation, oxidation, and ring-opening. Prediction of the toxicity of intermediates showed that the majority of TCs can be degraded into low-toxic or non-toxic, small-molecule products within 1 h, indicati …

Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity.

Obesity is a complex medical condition that is linked to various health complications such as infertility, stroke, and osteoarthritis. Under … reduces gene expression in the hypothalamus. Despite this, we found that CRISPR-dCas9-TET1-mediated demethylation of Pomc was not sufficient to prevent abnormal weight gain following exposure to a high fat diet. Furthermore, CRISPR-dCas9-DNMT3a-mediated methylation of Pomc did not alter weight gain following exposure to standard or high fat diets. Collectively, …