Histone H3 Recombinant Rabbit Monoclonal Antibody [43F02]

RNA modifications have emerged as crucial regulators of cellular processes linked to aging. However, the dynamic changes in global RNA modification patterns during aging and their functional implications remain underexplored. Here, we comprehensively deciphered the RNA modification landscapes of total RNA, poly(A)-enriched mRNA, and tRNA-enriched fragments across six tissues in both young and aged mice, as well as in multiple cellular senescence models. Aged tissues exhibit overall decline of RNA modification abundance in tRNA, rather than in total RNA or mRNA, when compared to young tissues. Correspondingly, the expression of tRNA methyltransferases, METTL1 and TRMT1, also declines with aging and senescence. Modulation of these methyltransferases affects cellular senescence phenotypes; specifically, Mettl1 depletion results in accelerated aging in mice. Mechanistically, fibroblasts are identified as the primary cell type responsible for the aging traits induced by Mettl1 deficiency in mice. Reduced m 7 G modification in fibroblasts leads to a decrease in the abundance of m 7 G-modified tRNAs, which in turn impairs translation efficiency and protein synthesis, and contributes to an accumulation of tRNA-derived small RNAs (tsRNAs). Remarkably, these alterations affected the translation of genes involved in senescence and aging pathways. Our study provides a comprehensive landscape of tRNA modifications during aging and demonstrates that decreased activity of METTL1 in fibroblasts drives aging. Thus, modulation of tRNA modifications may be a promising strategy for improving healthy aging and alleviating age-associated disorders.

Cancer-associated fibroblasts (CAFs) interact with tumor cells in the tumor microenvironment (TME), enhancing glycolysis in CAFs and tumor malignancy. However, the regulatory mechanisms between hepatoblastoma (HB) cells and CAFs are unclear. This study aimed to elucidate the crosstalk mechanism between HB cells and CAFs and identify a new therapeutic target for HB. Exosomes were successfully extracted from Huh-6/HepG2 cells, and hepatic stellate cells (LX2) were treated with conditioned medium or exosomes from these cells. We found that HB cells may stimulate the differentiation of LX2 cells into CAFs through exosomes and enhance histone lactylation. Additionally, HB cell exosome-derived fatty acid synthase (FASN) promoted the transformation of LX2 cells into CAFs and histone lactylation. Mechanistically, FASN affected the transformation of LX2 cells into CAFs and histone lactylation by regulating hexokinase 2 (HK2). FASN regulated HK2 stability by competitively combining with MARCHF1. Activated fibroblasts promoted HB progression by secreting CXCL1/CXCL5. In vivo experiments have demonstrated that HB cell exosome-derived FASN affected the transformation of LX2 cells into CAFs and histone lactylation. Clinical sample analysis revealed that FASN protein expression was significantly positively correlated with the levels of HK2, lactate, and H3K18la, thereby validating the clinical relevance of this regulatory pathway. In conclusion, HB-derived exosomal FASN affected the transformation of LX2 cells into CAFs by regulating the stability of HK2 and mediating histone lactylation, providing novel insights into the crosstalk between HB cells and CAFs and highlighting exosomal FASN as a potential therapeutic target for HB.

Background The aim of this study was to construct a prognostic model of colon cancer based on demethylation-related genes. An in-depth understanding of the relationship between the set of demethylated genes and colon cancer not only assists in revealing the pathogenesis of colon cancer but also provides strong support for future therapeutic strategies and individualized medicine. Methods Data were obtained from the TCGA database and the GEO-GSE39582 cohort. A risk score model for demethylation-related genes was developed using univariate Cox regression analysis and LASSO regression analysis. The accuracy and reliability of the model were confirmed using K–M survival analysis and ROC curve analysis. Additionally, a nomogram was created by integrating the risk score and clinicopathological variables. Finally, the biological function of the RCOR2 gene was verified by performing qPCR, MTT, colony formation, Transwell, and subcutaneous tumor formation assays in nude mice. Results We constructed a risk score model containing 30 demethylation-related genes for predicting the survival risk of patients with colon cancer. COAD patients were categorized into high-risk and low-risk groups, and Kaplan–Meier (KM) curve analysis revealed that the high-risk group was associated with a worse prognosis. Univariate and multivariate Cox regression analyses validated the risk score as an independent prognostic factor for COAD. We also analyzed the differences in the sensitivity to nine chemotherapeutic agents and small molecule targeted drugs between the high-risk and low-risk groups. Moreover, we performed experiments in COAD cell lines and nude mice to verify that RCOR2 was differentially expressed between tumor tissues and normal tissues and that high RCOR2 expression promoted a malignant phenotype of colon cancer. Conclusion This study demonstrated the potential roles of demethylation-related genes in colon cancer by conducting a comprehensive analysis and constructing a risk score. These findings also highlight the ability of these genes to indicate patient prognosis and tumor immune microenvironment. Furthermore, this study provides a reliable predictive tool that can assist in guiding the treatment and management of colon cancer patients.

Excessive inflammation is a prominent issue in diabetic wounds, leading to delayed healing or amputation. Corilagin (Cori) is a natural polyphenolic compound with diverse pharmacological activities, particularly its anti-inflammatory properties. The aim of this study was to evaluate the anti-inflammatory effect of Cori on diabetic wounds and to explore the potential underlying mechanisms. The impact of Cori on wound healing was assessed in streptozotocin (STZ)-induced diabetic mice through morphological observation, histological staining, and gene expression analysis. Flow cytometry, qRT-PCR, western blot analysis, and RNA sequencing were conducted to elucidate the underlying mechanisms in RAW264.7 cells. The results demonstrated that Cori accelerated wound healing, inhibited excessive inflammation, and regulated macrophage polarization in diabetic mice. In Vitro, Cori decreased M1 polarization and inhibited the expression of pro-inflammatory mediators in RAW264.7 cells. Sequencing analysis revealed that Cori exerts anti-inflammatory effects on RAW 264.7 cells through multiple targeted mechanisms. Moreover, in LPS-induced macrophages, Cori dramatically decreased the activation of TLR4, MyD88, and NF-κB. Additionally, Cori enhanced M2 polarization by promoting fatty acid oxidation. In conclusion, the findings suggest that Cori modulates macrophage polarization through various targeted mechanisms, effectively suppressing inflammation and accelerating diabetic wound healing. Graphical Diabetic ulcers are common chronic wounds marked by excessive and persistent inflammation, imposing significant healthcare and economic burdens. Corilagin (Cori) was shown to accelerate wound healing in STZ-induced diabetic mice by modulating macrophage polarization and suppressing inflammation. In vitro, Cori inhibited M1 polarization and reduced the expression of pro-inflammatory mediators via the TLR4/MyD88/NF-κB pathway, while promoting M2 polarization by enhancing fatty acid oxidation. This study highlights Cori's potential as a therapeutic agent for diabetic wound management through its multi-targeted anti-inflammatory mechanisms.