Search Results (79)

Cellular senescence is an intricate process that severely restricts stem cell function. The N6-methyladenosine (m⁶A) eraser, fat mass and obesity-associated (FTO) protein control several aspects of stem cell fate, including differentiation, self-renewal, and senescence. However, the role of FTO in dental pulp stem cell (DPSC) senescence has not yet been elucidated. This study aimed to explore the role of FTO in DPSC senescence. FTO expression decreases during DPSC senescence. FTO depletion inhibited DPSC proliferation, accelerated senescence, and increased reactive oxygen species (ROS) levels. FTO overexpression reduced DPSC senescence, enhanced proliferation, and decreased ROS accumulation. RNA sequencing demonstrated that FTO knockdown inhibited ribosomal RNA precursor (pre-rRNA) biogenesis. We found nucleolar and coiled-body phosphoprotein 1 (NOLC1) as a novel target of FTO. NOLC1 was upregulated after FTO knockdown and promoted DPSC senescence. Mechanistically, FTO downregulation increased the m⁶A modifications of NOLC1 mRNA, increasing the stability of the NOLC1 mRNA. NOLC1 upregulation inhibits the transcription of pre-rRNA, causing nucleolar stress and p53 accumulation. In addition, NOLC1 knockdown partially rescued FTO deficiency-induced DPSC senescence. Our findings identified the significant role of the FTO/NOLC1/p53 axis in DPSC senescence and provide new insights to prevent the aging of DPSCs, which is beneficial for the application of DPSCs in regenerative medicine and stem cell therapy. Full article

This study investigated the epigenetic mechanisms through which graded levels of dietary methionine (Met) regulates growth, muscle quality, and health in juvenile Megalobrama amblycephala fed an all-plant-protein diet. Dietary Met supplementation improved growth performance in a dose-dependent manner and enhanced muscle nutritional quality, particularly protein content and amino acid composition. Optimal Met intake also strengthened hepatic antioxidant defenses, stabilized mitochondrial function, and modulated plasma metabolite profiles, including metabolites associated with antioxidant, anti-inflammatory, and antimicrobial activity. Epigenetic analysis revealed that dietary Met influenced hepatic N⁶-methyladenosine (m⁶A) RNA methylation and the expression of genes involved in autophagy and apoptosis, suggesting that these molecular pathways contribute to the observed physiological benefits. Collectively, these findings indicate that appropriate dietary Met of 10.1 g/kg not only supports growth and nutrient utilization but also promotes metabolic and cellular homeostasis through epigenetic regulation. This work provides novel insights into the nutritional and molecular strategies for improving the health and performance of juvenile M. amblycephala under plant-based feeding regimes, with potential implications for sustainable aquaculture practices. Full article

Pediatric obesity is rising globally, and emerging evidence suggests that sleep timing may influence metabolic health through epigenetic mechanisms. This study investigated epigenome-wide DNA methylation patterns associated with bedtime in children and explored their biological relevance. Children aged 6–10 years were classified as early (≤8:30 PM) or late (>8:30 PM) bedtime groups. Saliva-derived DNA was analyzed using the Illumina Infinium MethylationEPIC BeadChip Array, and the Sparse Wrapper Algorithm (SWAG) was applied to identify differentially methylated loci. A total of 1006 CpG sites, representing 571 unique genes, were significantly associated with bedtime (p < 0.001). Significant methylation differences were observed between early and late bedtime groups, with ABCG2, ABHD4, MOBKL1A, AK3, SDE2, PRAMEF4, CREM, CDH4, BRAT1, and SDK1 showing the most consistent variation. Functional enrichment analyses (Gene Ontology, KEGG, and DisGeNET) conducted on the SWAG-identified gene set revealed enrichment in biological processes including peptidyl-lysin demethylation, regulation of sodium ion transport, DNA repair, and lipo-protein particle assembly. Key KEGG pathways included circadian entrainment, neurotransmission (GABAergic, dopaminergic, and glutamatergic), growth hormone synthesis, and insulin secretion. DisGeNET analysis identified associations with neurodevelopmental disorders and cognitive impairment. Cross-comparison with established sleep and obesity gene sets identified ten overlapping genes(CDH4, NR3C2, ACTG1, COG5, CAT, HDAC4, FTO, DOK7, OCLN, and ATXN1). These findings suggest that variations in bedtime during childhood may epigenetically modify genes regulating circadian rhythm, metabolism, neuronal connectivity, and stress response, potentially predisposing to later-life developmental, and metabolic challenges. Full article

N⁶-methyladenosine (m⁶A) has recently emerged as a post-transcriptional modulator governing cell-specific gene expression in innate immune cells, particularly in monocytes. Disruptions in m⁶A homeostasis, manifested as the altered expression of m⁶A-related proteins and m⁶A levels, have been implicated in autoimmune disorders. Perturbations in m⁶A dynamics within total Peripheral blood mononuclear cells (PBMCs) have shown strong correlations with disease severity in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It remains unclear in which specific cell type(s) m⁶A homeostasis is disturbed, and also whether other rheumatic diseases such as juvenile idiopathic arthritis (JIA) show similar features. Here, we assess the involvement of m⁶A and m⁶A-regulatory proteins in JIA monocytes. Notably, the diminished expression of m⁶A-eraser proteins FTO and ALKBH5 was observed in JIA monocytes extracted from the inflamed joint. This resulted in increased m⁶A-methylated transcripts in monocytes from these patients. Correspondingly, we observed that culturing monocytes in the presence of synovial fluid from JIA inflamed joints reduced the expression of both FTO and ALKBH5. The knock-out of FTO in human monocytes of healthy controls increased monocyte activation, indicating the relevance of FTO and m⁶A in the context of JIA. These findings underscore the potential of ALKBH5 and FTO expression as a biomarker in JIA and identify the m⁶A machinery as a potential therapeutic target for the treatment of JIA and possibly other autoimmune diseases in the future. Full article

Resveratrol (RES), a natural polyphenol with lipid metabolism-regulating properties, also demonstrates remarkable efficacy in strengthening intestinal barrier integrity. In order to elucidate the mechanism by which RES ameliorates intestinal damage and lipid metabolism disturbances in Megalobrama amblycephala under a high-fat (HF) diet, a conventional diet (CON), an HF diet (HF), or an HF diet supplemented with 0.6, 3, or 6 g/kg RES (HF + 0.06%, 0.3%, or 0.6% RES) was fed to fish. After 8 weeks, RES supplementation in the HF diet significantly improved the growth performance and alleviated hepatic lipid deposition. Microbiota profiling revealed RES improved intestinal barrier function by reducing α-diversity, Actinobacteria and Bosea abundances, and enriching Firmicutes abundance. RES also maintained the integrity of the intestinal physical barrier and inhibited the inflammatory response. MeRIP-seq analysis indicated that RES modulated intestinal mRNA m⁶A methylation by upregulating methyltransferase-like 3 (mettl3) and downregulating fat mass and obesity-associated gene (fto) and Alk B homolog 5 (alkbh5). Combined RNA-seq and MeRIP-seq data revealed that RES alleviated endoplasmic reticulum stress (ERS) by upregulating the m⁶A methylation and gene level of heat shock protein 70 (hsp70). Correlation analyses identified significant associations between intestinal microbiota composition and ERS, tight junction, and inflammation. In summary, RES ameliorates lipid dysregulation via a synergistic mechanism involving intestinal microbiota, m⁶A modification, ERS, barrier function, and inflammatory response. Full article

Asthma is a chronic inflammatory airway disease influenced by both genetic and environmental factors. Recent insights have underscored the pivotal role of epigenetic regulation in the pathogenesis and heterogeneity of asthma. This review focuses on key epigenetically important regulators categorized as writers, erasers, and readers that govern DNA methylation, histone modifications, and RNA modifications. These proteins modulate gene expression without altering the underlying DNA sequence, thereby influencing immune responses, airway remodeling, and disease severity. We highlight the structural and functional dynamics of histone acetyltransferases (e.g., p300/CBP), histone deacetylases (e.g., SIRT family), DNA methyltransferases (DNMT1, DNMT3A), demethylases (TET1), and methyl-CpG-binding proteins (MBD2) in shaping chromatin accessibility and transcriptional activity. Additionally, the m6A RNA modification machinery including METTL3, METTL14, FTO, YTHDF1/2, IGF2BP2, and WTAP is explored for its emerging significance in regulating post-transcriptional gene expression during asthma progression. Structural characterizations of these proteins reveal conserved catalytic domains and interaction motifs, mirroring their respective families such as SIRTs, p300/CBP, DNMT1/3A, and YTHDF1/2 critical to their epigenetic functions, offering mechanistic insight into their roles in airway inflammation and immune modulation. By elucidating these pathways, this review provides a framework for the development of epigenetic biomarkers and targeted therapies. Future directions emphasize phenotype-specific epigenomic profiling and structure-guided drug design to enable precision medicine approaches in asthma management. Full article

Background: The function and mechanism of N6-methyladenosine (m6A) methylation in pressure-overload cardiac fibrosis remains limited and unclear. This study aims to analyze and predict m6A modifications present in mouse hearts because of transverse aortic constriction (TAC). Materials and Methods: Twelve male C57BL/6 mice were randomly assigned to two groups, TAC group and sham group. The RNA Dot Blot assay was employed to evaluate the overall m6A methylation levels in both TAC and sham mice. The expression level of m6A-related enzymes were investigated through RT-PCR and Western blotting. MeRIP-seq and RNA-seq analyses were conducted to identify differentially modified m6A genes and mRNA expression genes. The protein–protein interaction (PPI) network was carried out to choose potential hub genes. Additionally, the transcription factor (TF)–microRNA (miRNA) coregulatory network and the drug–hub gene interaction network were built based on these hub genes. Furthermore, molecular docking simulations were also performed to analyze the interactions between drugs and hub genes. Results: Compared with the sham group, the TAC group demonstrated elevated levels of global m6A methylation. METTL3 and METTL14 were significantly upregulated, whereas FTO and ALKBH5 were significantly downregulated following TAC. MeRIP-seq analysis identified 17,806 m6A peaks associated with 9184 genes and 16,392 m6A peaks associated with 8550 genes in the TAC and sham groups, respectively. In conjunction with RNA-seq data, 66 genes were identified as exhibiting concurrent differences in both m6A methylation levels and mRNA expression. Six hub genes, Cd33, Irf4, Nr4a2, Hspa1b, Nr4a1, and Adcy1, were identified through the construction of a PPI network. The TF-miRNA coregulatory network contains six hub genes, 31 miRNAs, and 24 TFs. The drug–hub genes interaction network included five hub genes and 36 candidate drugs. Conclusions: The m6A modification is prevalent in TAC-induced cardiac fibrosis and significantly contributes to the fibrotic process by regulating critical genes. In the future, it may emerge as one of the potential cardiac fibrosis therapeutic targets. Full article

Obesity is a global health challenge marked by substantial inter-individual differences in responses to dietary and lifestyle interventions. Traditional weight loss strategies often overlook critical biological variations in genetics, metabolic profiles, and gut microbiota composition, contributing to poor adherence and variable outcomes. Our primary aim is to identify key biological and behavioral effectors relevant to precision medicine for weight control, with a particular focus on nutrition, while also discussing their current and potential integration into digital health platforms. Thus, this review aligns more closely with the identification of influential factors within precision medicine (e.g., genetic, metabolic, and microbiome factors) but also explores how these factors are currently integrated into digital health tools. We synthesize recent advances in nutrigenomics, nutritional metabolomics, and microbiome-informed nutrition, highlighting how tailored dietary strategies—such as high-protein, low-glycemic, polyphenol-enriched, and fiber-based diets—can be aligned with specific genetic variants (e.g., FTO and MC4R), metabolic phenotypes (e.g., insulin resistance), and gut microbiota profiles (e.g., Akkermansia muciniphila abundance, SCFA production). In parallel, digital health tools—including mobile health applications, wearable devices, and AI-supported platforms—enhance self-monitoring, adherence, and dynamic feedback in real-world settings. Mechanistic pathways such as gut–brain axis regulation, microbial fermentation, gene–diet interactions, and anti-inflammatory responses are explored to explain inter-individual differences in dietary outcomes. However, challenges such as cost, accessibility, and patient motivation remain and should be addressed to ensure the effective implementation of these integrated strategies in real-world settings. Collectively, these insights underscore the pivotal role of precision nutrition as a cornerstone for personalized, scalable, and sustainable obesity interventions. Full article

Background/Objectives: The fat mass and obesity-associated (FTO) protein demethylates nuclear N6-Methyladenosine (m6A) on mRNA, facilitates tumor growth, and contributes to therapeutic resistance in multiple cancer types. Recent evidence demonstrates several roles of FTO in tumorigenesis. In this study, we seek to explore the role of FTO in non-small cell lung cancer (NSCLC) tumorigenicity and its relationship with epidermal growth factor receptor (EGFR) tyrosine kinase resistance. Methods: We performed qPCR, immunoblotting, viability assays, migration assays, and ATP assays to investigate the functions of FTO in EGFR tyrosine kinase inhibitor (TKI) resistance, specifically to erlotinib, in three NSCLC cell lines harboring either wild-type or mutant EGFR. We also performed immunohistochemistry on lung tumor tissues from patients diagnosed at different stages of NSCLC. Results: Our study found an upregulation of FTO in erlotinib-resistant (ER) cell lines at both the gene and protein levels. FTO inhibition and knockdown significantly reduced cell viability of erlotinib-resistant H2170 and PC9 cells by over 30% when treated with 0.8 µM of Dac51 and about 20% when treated with siFTO. FTO inhibition also slowed down the migration of ER cells, and the effect was even more pronounced when combined with erlotinib. Furthermore, FTO was found to be overexpressed in late-stage NSCLC tumor tissues compared to early-stage tumors, and it was upregulated in patients who smoked. Conclusions: These findings suggest FTO might mediate resistance and tumor growth by augmenting cell proliferation. In addition, FTO can be a potential prognostic marker in NSCLC patients. Full article

The objective of this study was to identify the AlkB family genes in poultry using bioinformatics, and to explore their molecular characteristics, evolutionary relationships, and expression patterns to clarify their potential functions in poultry. (1) Methods: The study utilized the NCBI database to obtain chicken genome data, and screened and validated AlkB family members (ALKBH1-5, ALKBH8, and FTO) by hmmsearch and TBtools. MEGA 11.0 was used for phylogenetic analysis, PHYRE2 and I-TASSER predicted protein structures, and the String database was used to construct an interoperability network. Finally, the tissue expression profiles were analyzed by using The Human Protein Atlas online database and qRT-PCR. (2) Results: Phylogenetic analysis revealed distinct avian and mammalian clusters, with chicken AlkB proteins exhibiting low sequence homology but conserved 3D structures compared to mammals. Chromosomal synteny and conserved domains highlighted evolutionary divergence, with ALKBH4 lacking typical AlkB structural motifs. Protein interaction networks linked ALKBH1/2/3/5/8/FTO, underscoring functional coordination in poultry adaptation. Tissue-specific expression showed high AlkB levels in brain tissues, while ALKBH5 dominated in muscle. During differentiation, ALKBH3, ALKBH5, and FTO expression significantly increased during myoblast differentiation. (3) Conclusions: This study identified seven AlkB family genes in poultry, revealing their phylogenetic classification into two subfamilies, conserved structural domains, chromosomal synteny, and tissue-specific expression patterns. Full article

FTO expression correlates with adipose tissue development in rabbits, yet its regulatory role in preadipocyte differentiation remains poorly understood. Therefore, we employed transcriptome sequencing to identify 422 differentially expressed genes (DEGs) between the FTO overexpression group and the FTO-negative control group. Multi-omics evidence from proliferation assays (CCK-8), protein verification (WB), gene quantification (qPCR), and lipid staining (Oil Red O) established FTO as a positive regulator of rabbit preadipocyte development with gain-of-function enhancing and loss-of-function impeding differentiation. In conclusion, FTO regulates the proliferation and differentiation of rabbit preadipocytes, providing deeper insights into livestock energy metabolism and physiological functions. These findings hold significant implications for healthy animal farming, high-quality livestock product production, and the prevention and control of metabolic diseases in animals. Full article

Kalanchoe pinnata is used in traditional medicine to treat cancer, as it contains flavonoids and phenols known to regulate key cellular processes associated with cancer. Breast cancer, the most common cancer among women globally, presents ongoing challenges in treatment. The discovery of m⁶A methylation and its regulation by methylosome proteins offers novel therapeutic avenues for cancer management. This study aimed to investigate the cytotoxic and epitranscriptomic effects of an aqueous extract from K. pinnata on MCF-7 (luminal A) and HCC1937 (triple-negative) breast cancer cells. Cell lines were treated with the aqueous K. pinnata extract, characterized by HPLC, for 72 h, followed by an assessment of cytotoxicity and migration. The expression of methylosome components METTL3 and FTO was measured using RT-PCR. m⁶A global methylation was assessed via colorimetry, and molecular docking studies were conducted. The results indicated that only HCC1937 cells exhibited altered migration capacity. This change was correlated in silico with the inhibition of METTL3 by luteolin and quercetin, constituents of the aqueous extract. METTL3, a methyltransferase, was overexpressed by scratch stimuli but was downregulated following K. pinnata treatment in both MCF-7 and HCC1937 cells. The FTO demethylase was overexpressed in both cell lines. In silico analysis suggested an interaction between FTO and compounds such as gallic acid and myricetin. Additionally, m⁶A global methylation decreased in MCF-7 cells but increased in HCC1937 cells, potentially affecting cell migration. Our findings indicate that K. pinnata influences both METTL3 and FTO, altering m⁶A methylation in a cell-type-dependent manner, with HCC1937 cells being particularly sensitive. Further research is required to elucidate the complete molecular mechanism of K. pinnata’s aqueous extract in breast cancer treatment. Full article

Prolonged breastfeeding (BF), as opposed to artificial infant formula feeding (FF), has been shown to prevent the development of obesity later in life. The aim of our narrative review is to investigate the missing molecular link between postnatal protein overfeeding—often referred to as the “early protein hypothesis”—and the subsequent transcriptional and epigenetic changes that accelerate the expansion of adipocyte stem cells (ASCs) in the adipose vascular niche during postnatal white adipose tissue (WAT) development. To achieve this, we conducted a search on the Web of Science, Google Scholar, and PubMed databases from 2000 to 2025 and reviewed 750 papers. Our findings revealed that the overactivation of mechanistic target of rapamycin complex 1 (mTORC1) and S6 kinase 1 (S6K1), which inhibits wingless (Wnt) signaling due to protein overfeeding, serves as the primary pathway promoting ASC commitment and increasing preadipocyte numbers. Moreover, excessive protein intake, combined with the upregulation of the fat mass and obesity-associated gene (FTO) and a deficiency of breast milk-derived microRNAs from lactation, disrupts the proper regulation of FTO and Wnt pathway components. This disruption enhances ASC expansion in WAT while inhibiting brown adipose tissue development. While BF has been shown to have protective effects against obesity, the postnatal transcriptional and epigenetic changes induced by excessive protein intake from FF may predispose infants to early and excessive ASC commitment in WAT, thereby increasing the risk of obesity later in life. Full article

Background/Objectives: RNA-modifying proteins play a crucial role in the progression of cancer. The fat mass and obesity-associated protein (FTO) and alkB homolog 5 RNA demethylase (ALKBH5) are RNA-demethylating proteins that have contrasting effects in renal cell carcinoma (RCC) among different populations. This research investigates the genotype and expression levels of FTO and ALKBH5 in RCC patients from the Middle East and Northern Africa (MENA) region. Methods: Formalin-fixed paraffin-embedded samples from the kidney biopsies of RCC patients and controls were examined using targeted DNA sequencing, whole transcriptome profiling, and immunohistochemistry. Results: Our findings show that the rs11075995T variant in FTO is associated with a heightened risk of clear-cell RCC (ccRCC). ALKBH5 and FTO protein expression were significantly lower in ccRCC and chromophobe RCC (chRCC) patients but not in papillary RCC (pRCC) patients. In ccRCC, transcriptomic data revealed a significant downregulation of FTO (log₂FC = −5.2, q < 0.001) and ALKBH5 (log₂FC = −4.7, q < 0.001) compared to controls. A significant negative correlation was found in ccRCC between FTO expression and T allele frequency in rs11075995, suggesting that FTO expression is affected. Conclusions: This is the first demonstration of the association of the dysregulated expression of FTO and ALKBH5 in ccRCC and chRCC patients from the MENA region. FTO variant rs11075995T increased the risk of ccRCC and was negatively associated with FTO protein expression. Full article

Phaeodactylum tricornutum is rich in bioactive substances, rendering it valuable in nutrition and medicine. Epigenetic editing mediated by human RNA demethylase FTO can significantly increase the yields of rice and potato and offers significant potential for the genetic breeding of microalgae. This study aimed to enhance the production of certain metabolites in P. tricornutum via FTO-mediated epigenetic editing. Phenotypic analysis revealed that transgenic P. tricornutum exhibits significantly reduced RNA m⁶A modification levels and faster growth, producing markedly higher levels of lipids, proteins, and carotenoids than the wild type. Transcriptome analysis revealed 1009 upregulated genes and 378 downregulated genes. KEGG analysis demonstrated the upregulated expression of multiple key enzymes involved in long-chain fatty acid synthesis (e.g., ACSL, fabF, and fabG), carotenoid synthesis (e.g., crtQ, PDS, and PSY1), and amino acid synthesis (e.g., dapF, glyA, and aroK) in transgenic P. tricornutum, consistent with our phenotypic results. These results indicate that FTO can promote growth and increase the bioactive compound content in P. tricornutum by regulating the m⁶A modification of RNA, and further suggest that FTO has the potential to serve as a new tool for the epigenetic editing of microalgae. Full article