Roseburia intestinalis Supplementation Could Reverse the Learning and Memory Impairment and m6A Methylation Modification Decrease Caused by 27-Hydroxycholesterol in Mice

Nutrients, Journal Year: 2024, Volume and Issue: 16(9), P. 1288 - 1288

Published: April 26, 2024

The abnormality in N6-methyladenosine (m6A) methylation is involved the course of Alzheimer’s disease (AD), while intervention 27-Hydroxycholesterol (27-OHC) can affect m6A modification brain cortex. Disordered gut microbiota a key link 27-OHC leading to cognitive impairment, and further studies have found that abundance Roseburia intestinalis significantly reduced under 27-OHC. This study aims investigate association 27-OHC, gut, learning memory ability injury. In this study, 9-month-old male C57BL/6J mice were treated with antibiotic cocktails for 6 weeks sweep intestinal flora, followed by or normal saline subcutaneous injection, then gavage applied mouse. level brain, barrier function, measured. From results, we observed impairs causing disturbance expression methylation-related enzymes reducing cortex, finally leads impairment. However, supplementation could reverse negative effects mentioned above. suggests 27-OHC-induced impairment might be linked disturbance, intestinalis, as probiotic great potential, damage caused research help reveal mechanism neural provide important scientific evidence future use neuroprotection.

Language: Английский

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NSUN2-Mediated RNA 5-Methylcytosine Modification of PTEN Regulates Cognitive Impairments of Mice with Sleep Deprivation and Autophagy Through PI3K/AKT Signaling

NeuroMolecular Medicine, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 4, 2025

Language: Английский

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The complex roles of m6A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(6), P. 1582 - 1598

Published: June 3, 2024

N6-methyladenosine (m 6 A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. plays crucial roles neural stem cell genesis regeneration, where it is highly concentrated actively involved these processes. Changes m A levels expression related enzymatic proteins can lead to neurological dysfunction contribute development diseases. Furthermore, proliferation differentiation as well nerve are intimately linked memory function neurodegenerative This paper presents a comprehensive review proliferation, differentiation, self-renewal, its implications has demonstrated divergent effects on cells. These observed contradictions may arise from time-specific nature differential impact cells across various stages development. Similarly, diverse distinct types could be attributed involvement specific brain regions formation recall. Inconsistencies different models disease, particularly Alzheimer's disease Parkinson's suggest that disparities variations affected regions. Notably, opposing changes exposed manganese compared normal further underscore complexity A's role The diseases, appear contradictory. inconsistencies varying environments.

Language: Английский

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Comprehensive landscape of m6A regulator-related gene patterns and tumor microenvironment infiltration characterization in gastric cancer

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 16, 2024

Abstract The epigenetic regulation of N6-methyladenosine (m 6 A) has attracted considerable interest in tumor research, but the potential roles m A regulator-related genes, remain largely unknown within context gastric cancer (GC) and microenvironment (TME). Here, a comprehensive strategy data mining computational biology utilizing multiple datasets based on 28 regulators (including novel anti-readers) was employed to identify genes patterns elucidate their underlying mechanisms GC. Subsequently, scoring system constructed evaluate individual prognosis immunotherapy response. Three distinct were identified through unsupervised clustering 56 (all significantly associated with GC prognosis). TME characterization revealed that these highly corresponded immune-inflamed, immune-excluded, immune-desert phenotypes, characteristics consistent different clinical outcomes biological processes. Additionally, an A-related developed quantify modification pattern samples. Low scores indicated high survival rates levels immune activation, whereas stromal activation malignancy. Furthermore, correlated mutation loads various traits, including molecular or histological subtypes stage grade, score had predictive values across all digestive tumors even types. Notably, low linked improved responses anti-PD-1/L1 anti-CTLA4 three independent cohorts. This study expanded important role shaping diversity clinical/biological traits could help develop more effective strategies personalized treatment guidance.

Language: Английский

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METTL Family in Healthy and Disease

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Aug. 19, 2024

Abstract Transcription, RNA splicing, translation, and post-translational protein modification are fundamental processes of gene expression. Epigenetic modifications, such as DNA methylation, play a crucial role in regulating The methyltransferase-like (METTL) family, constituent the 7-β-strand (7BS) methyltransferase subfamily, is broadly distributed across cell nucleus, cytoplasm, mitochondria. Members METTL through their S-adenosyl methionine (SAM) binding domain, can transfer methyl groups to DNA, RNA, or proteins, thereby impacting replication, transcription, mRNA participate maintenance normal function promote disease development. This review primarily examines involvement family differentiation, mitochondrial function, its association with tumor formation, nervous system, cardiovascular diseases. Notably, intricately linked cellular particularly regulation translation factors. represent important molecules development associated patient immunity tolerance radiotherapy chemotherapy. Moreover, future research directions could include drugs antibodies targeting structural domains, utilizing nanomaterials carry miRNA corresponding mRNA. Additionally, precise mechanisms underlying interactions between factors remain be clarified.

Language: Английский

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MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis

Veterinary Research, Journal Year: 2025, Volume and Issue: 56(1)

Published: Feb. 4, 2025

Abstract Trichinella spiralis ( T. ) has been reported to induce inflammation, which can cause immune system dysregulation. Myeloid differentiation primary response gene 88 (MyD88) is implicated in inflammation signalling pathways. TJ-M2010-5 a novel MyD88 inhibitor with remarkable protective effects against several diseases. However, the precise mechanism of TJ-M2010-5’s involvement spleen impairment and early infection yet be fully elucidated. This study analysed histological, macrophage polarisation -infected mice treated TJ-M2010-5. promoter methylation results showed that levels 5 d group were lower compared control P < 0.05). Furthermore, led an imbalance anti-inflammatory regulation infected mice. After treatment, was reduced. Sequencing analysis significantly up-regulated 9 down-regulated 10 miRNAs group. A dual-luciferase reporter assay further revealed miR-136-5p involved treatment by targeting AKT3. In RAW264.7 cells, pre-treatment reversed M1 inhibited nitric oxide (NO) production. LC–MS/MS hepatosplenic-targeted. conclusion, demonstrates could effectively alleviate reduce its stages blocking activation PI3K/miR-136-5p/AKT3.

Language: Английский

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Modification of the RNA methylome in neurodevelopmental disorders

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102330 - 102330

Published: March 12, 2025

RNA metabolism is fundamental to protein synthesis, degradation and transport of molecules. Methylation influences the processing mRNA, noncoding RNA, tRNA rRNA. Here, we review accumulating evidence that disruption methylome impairs developmental processes causes neurodevelopmental conditions. We first describe mutated methylation effector genes give rise syndromes. consider biological thereby disrupted, including translational dynamics at cytoplasmic mt-ribosomes, synaptic function, energy production cellular stress. Finally, discuss novel forms methylated such as R-loops circular RNAs, which may contribute disease processes. These findings herald an exciting new era brain research highlight significant potential manipulating a therapeutic target in treatment disorders.

Language: Английский

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Biallelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a neurodevelopmental disorder

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

The post-transcriptional modification of tRNAs plays a crucial role in tRNA structure and function. Pathogenic variants tRNA-modification enzymes have been implicated wide range human neurodevelopmental neurological disorders. However, the molecular basis for many these disorders remains unknown. Here, we describe comprehensive cohort 43 individuals from 31 unrelated families with bi-allelic methyltransferase 1 (TRMT1). These present disorder universally characterized by developmental delay intellectual disability, accompanied variable behavioral abnormalities, epilepsy, facial dysmorphism. identified include ultra-rare TRMT1 variants, comprising missense predicted loss-of-function which segregate observed clinical pathology. Our findings reveal that several lead to mis-splicing consequent loss protein accumulation. Moreover, cells derived harboring exhibit deficiency modifications catalyzed TRMT1. Molecular analysis reveals distinct regions required activity binding. Notably, depletion Trmt1 zebrafish is sufficient induce phenotypes along gene-expression changes associated disrupted cell cycle, immune response, neurodegenerative Altogether, demonstrate TRMT1-catalyzed leads disability provides insight into underpinnings caused pathogenic variants.

Language: Английский

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Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2880 - 2880

Published: March 1, 2024

Traumatic brain injury (TBI) can lead to post-traumatic epilepsy (PTE). Blast TBI (bTBI) found in Veterans presents with several complications, including cognitive and behavioral disturbances PTE; however, the underlying mechanisms that drive long-term sequelae are not well understood. Using an unbiased proteomics approach a mouse model of repeated bTBI (rbTBI), this study addresses gap knowledge. After rbTBI, mice were monitored using continuous, uninterrupted video-EEG for up four months. Following period, we collected cortex hippocampus tissues from three groups mice: those (PTE+), without (PTE−), control group (sham). Hundreds differentially expressed proteins identified PTE+ PTE− relative sham. Focusing on protein pathways unique PTE+, related mitochondrial function, post-translational modifications, transport disrupted. Computational metabolic modeling dysregulated expression predicted proton pump dysregulation, suggesting electron chain dysregulation epileptic tissue PTE−. Finally, data mining enabled identification novel previously validated biomarkers our set, many which already be targeted by drugs various phases clinical testing. These findings highlight may chronic PTE following rbTBI.

Language: Английский

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Regulatory effect of N6-methyladenosine on tumor angiogenesis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 4, 2024

Previous studies have demonstrated that genetic alterations governing epigenetic processes frequently drive tumor development and modifications in RNA may contribute to these alterations. In the 1970s, researchers discovered N6-methyladenosine (m

Language: Английский

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