Nucleosides, Nucleotides & Nucleic Acids最新文献

RECK plays an important role in the development of cancer. The current study focuses on exploring the clinical significance of RECK expression in cancer by mining public data and also evaluating the relationship between genetic polymorphisms of the RECK gene and cancer risk through meta-analysis. The results showed that RECK expression was not only associated with survival prognosis and immune infiltration in many types of cancers, but also with multiple drug sensitivity in pan-cancer. In addition, the RECK rs10814325 polymorphism was also associated with cancer risk under the homozygote comparison model (CC vs. TT: OR = 1.64, 95%CI = 1.03-2.61, p = 0.04) and the recessive genetic model [CC vs. (CT + TT): OR = 1.55, 95%CI = 1.27-1.89, p < 0.01]. In conclusion, these findings suggest that RECK expression levels may serve as a valuable indicator for assessing cancer prognosis in some cancers as well as drug sensitivity in pan-cancer, and its rs10814325 polymorphism may be used to assess cancer risk.

Objective: Intervertebral disk degeneration (IVDD) is one of the most common causes of low back pain. However, in the etiology of IVDD, the specific method by which nucleus pulposus (NP) cell senescence and the immune response induce disease is uncertain.

Methods: Gene Expression Omnibus database was used to find differentially expressed genes (DEGs), differentially expressed miRNAs (DE miRNAs), differentially expressed lncRNAs (DE lncRNAs), and differentially expressed circRNAs (DE circRNAs). Functional enrichment analysis was performed through Enrichr database. Potential regulatory miRNAs, lncRNAs and circRNAs of mRNAs were predicted by ENCORI and circBank, respectively.

Results: We identified 198 upregulated and 131 downregulated genes, 39 upregulated and 22 downregulated miRNAs, 2152 upregulated and 564 downregulated lncRNAs, and 352 upregulated and 279 downregulated circRNAs as DEGs, DE miRNAs, DE lncRNAs, DE circRNAs, respectively. Functional enrichment analysis revealed that they were significantly enriched in Toll-like receptor signaling route and the NF-kappa B signaling pathway. An mRNA-miRNA-lncRNA/circRNA network linked to the pathogenesis of NP cells in IVDD was constructed based on node degree and differential expression level. Eight immune-related DEGs (6 upregulated and 2 downregulated genes) and five aging-related DEGs (3 upregulated and 2 downregulated genes) were identified in the critical network.

Conclusion: We established a novel immune-related and aging-related triple regulatory network of mRNA-miRNA-lncRNA/circRNA ceRNA, among which all RNAs may be utilized as the pathogenesis biomarker of NP cells in IVDD.

Objective: To conduct a meta-analysis and a bioinformatics analysis to assess the relationship between IGF2BP2 gene polymorphism and pan-cancer risk.

Methods: PubMed, EMBASE, and Web of Science were conducted to literature searches. The heterogeneity test was used in five genetic models. Odds ratios (OR), 95% confidence intervals (CI), and p-values were used to evaluate the combined effects of various genetic models. Subgroup analysis and Meta-regression analysis were used to analyze the characteristics of heterogeneity. Sensitivity analysis and publication bias were also performed. Transcriptomic information on IGF2BP2 was downloaded and analyzed from the TCGA and GTEx databases. GEPIA (http://gepia.cancer-pku.cn/) was performed to analyze the relationship between IGF2BP2 expression and cancer tissue.

Results: This meta-analysis contained 7 case-control studies, with 5,908 cases and 7,890 controls. There were significant differences in the heterozygous genetic model of IGF2BP2 gene rs4402960 polymorphism (OR = 1.080, 95% CI = 1.003-1.163, p = 0.041). In subgroup analysis based on ethnicity, There was a statistical significant association in Chinese (heterozygous: OR = 1.110, 95% CI = 1.010-1.220, p = 0.030). Bioinformatics analysis found that IGF2BP2 was over-expressed in pan-cancer (p < 0.01). In addition, the Kaplan-Meier estimate showed that there is statistical significance of OS between the low and high IGF2BP2 TPM groups in Lung adenocarcinoma (p <0.001).

Conclusions: To sum up, IGF2BP2 gene polymorphism may be related to cancer risk. IGF2BP2 has diagnostic value in the diagnosis and treatment of pan-cancer.

5-Fluorouracil (5-FU) is a commonly used anticancer drug for colorectal cancer (CRC). Therefore, it is crucial to elucidate the mechanisms that contribute to 5-FU resistance. We established an acquired 5-FU resistant cell line, HCT116R^F10, derived from CRC cells and investigated its energy metabolism as well as the underlying mechanism of 5-FU resistance. We examined the sensitivity to 5-FU and the formation of tumor spheres in parental HCT116 cells and 5-FU-resistant HCT116R^F10 cells under 3D culture conditions at high-glucose (HG 25 mM) and low-glucose (LG 5.5 mM) concentrations. These results suggested that the tumor spheres of parental HCT116 cells displayed higher sensitivity to 5-FU under LG conditions than under HG conditions. HCT116R^F10 tumor spheres exhibited comparable sensitivity to 5-FU under HG and LG conditions. Furthermore, under HG conditions, there was a marked decrease in extracellular lactate in the HCT116R^F10 tumor sphere compared to that in the LG tumor sphere. Similarly, HCT116 tumor spheres showed decreased extracellular lactate levels under LG conditions compared to those grown under HG conditions. Moreover, the evidence reveals that the tumor spheres of HCT116R^F10 and HCT116 cells exhibit disparate dependencies on energy metabolism, glycolysis, and mitochondrial respiration under both HG and LG conditions. These results have important clinical implications for overcoming 5-FU resistance and enhancing antitumor treatment strategies.

Nucleoside derivatives are important therapeutic drugs that have drawn significant attention recently. In this study, cytidine (1) was first exposed to react with cinnamoyl chloride in N,N-dimethylformamide, and trimethylamine to obtain 5'-O-(cinnamoyl)cytidine, which was further treated with several acylating agents to obtain a series of 2',3'-di-O-acyl derivatives. The chemical structures of the synthesized compounds were established through spectral, analytical, and physicochemical techniques. In vitro antimicrobial efficacy was evaluated, and the antimicrobial effect was greater than that of the precursor compound; in particular, compound 3 exhibited the most promising activity. Cytotoxicity measurements revealed that the compounds demonstrated a decreased degree of toxicity. A structure-activity relationship (SAR) study showed that the ribose moiety combined with the acyl chains (C-12/C13) and (C₆H₅CH = CHCO) had enhanced effects on bacteria and fungi. Molecular docking was applied for the potential inhibitors (3, 4, and 6) to predict their mode of action and confirm their efficacy against isozymes, tubulin-like protein TubZ, Bacillus cereus [PDB: 4ei9], and dihydrofolate reductase of Aspergillus flavus [PDB: 6dtc]. A molecular dynamics simulation study was performed to evaluate the deformability, flexibility, and stiffness of the target enzyme residues. Density functional theory (DFT) indicates the high polarizability and chemical reactivity of the synthesized compounds. The ADMET (absorption, distribution, mechanism, excretion, and toxicity) study suggested that all the designed molecules have moderate human intestinal absorption and good distribution values in addition to the absence of CNS side effects and structural toxicity. Above all else, these cytidine derivatives possess potential antimicrobial behavior, thereby rendering them suitable drug candidate(s) for additional exploration.

MicroRNA-134 (miRNA134) has emerged as a critical regulator in the pathogenesis of epilepsy, particularly in intractable cases resistant to conventional therapies. This review explores the multifaceted roles of miRNA134 in epileptogenesis, focusing on its influence on dendritic spine morphology and synaptic plasticity. Through its interactions with proteins such as LIM kinase 1 (LIMK1), Pumilio 2 (PUM2), and Tubby-like protein 1 (TULP1), miRNA134 modulates various molecular pathways implicated in epilepsy development. Preclinical studies have shown pro-mising results in targeting miRNA134 for mitigating seizure activity, highlighting its potential as a therapeutic target. Furthermore, miRNA134 holds promise as a biomarker for epilepsy diagnosis and prognosis, offering opportunities for personalized treatment approaches. However, further research is warranted to elucidate the precise mechanisms underlying miRNA134's effects and to translate these findings into clinical applications.