5-Methylcytosine (m₅C) has attracted increasing attention as an important epitranscriptomic modification that regulates RNA metabolism and diverse cellular processes. It is dynamically controlled by writer, eraser, and reader proteins that govern the life cycle of the methylated transcript. Studies have demonstrated that aberrant m₅C enzymatic dysregulation is linked to a wide range of human diseases, ranging from non-communicable diseases like cancer to communicable diseases like viral infections. Notably, m₅C regulatory enzymes may exert context-dependent dual roles, functioning either protectively or pathogenically within and across different disease settings. However, current research efforts remain largely confined to individual disease models, and a unified understanding of m₅C functions across pathologies remains lacking. Furthermore, clinical translation targeting m₅C modification remains limited, with most findings restricted to experimental studies. This review aims to provide a comprehensive overview of current knowledge on m₅C-mediated mechanisms across both communicable and non-communicable contexts and evaluate their potential as therapeutic targets.

Alzheimer’s disease is a prevalent neurodegenerative disease that is characterized by synaptic dysfunction followed by neuronal loss. The core pathological mechanisms of Alzheimer’s disease include the extracellular deposition of amyloid beta (Aβ) plaques and intracellular neurofibrillary tangle deposits inside the brain. These pathological hallmarks initiate the activation of neuro-immunological pathways that lead to neuronal loss. Aβ aggregation and neurofibrillary tangles function as danger signals and cause the release of extracellular adenosine‑5′‑triphosphate (ATP) from stressed or damaged neurons. The released ATP further amplifies the neuroinflammatory response by activating the P2X7 receptor (P2X7R) on microglial cells, which in turn facilitates NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome complex formation and activation. The latter event leads to caspase-1 activation-mediated release of cytokines, including interleukin-1β and interleukin-18, followed by pyroptotic cell death. Consequently, this neuroinflammatory cascade results in cognitive impairment. Despite intensive research efforts, direct therapeutic targeting of the P2X7R has yielded limited clinical success, partly due to receptor compensatory mechanisms and genetic polymorphisms that affect treatment responsiveness. In this context, emerging evidence highlights the potential of targeting the downstream NLRP3 inflammasome via natural bioactive compounds or synthetic molecules as a more promising therapeutic strategy for modulating the neuroinflammatory pathways underlying Alzheimer’s pathogenesis. Collectively, this review summarizes the progressive molecular events linking Aβ and tau pathology to neuroinflammation via the P2X7R-NLRP3 inflammasome axis, while underscoring the therapeutic potential of plant-derived bioactive compounds as well as synthetic molecules in mitigating the progression of Alzheimer’s disease.

Objective: To evaluate the effects of total flavonoids of Selaginella tamariscina (Beauv.) Spring (TFST) on glucolipid metabolic disorders (GLMD) in rats and TNF-α-stimulated human umbilical vein endothelial cells, as well as elucidate the underlying mechanisms.
Methods: A rat model of GLMD was established using a high-fat diet combined with vitamin D₃. Body weight and liver weight were recorded, and serum lipid profiles and biochemical parameters were determined. Hepatic histopathological changes were evaluated using hematoxylin and eosin (H&E) staining. The potential mechanisms underlying the protective effects of TFST against vascular inflammation were further explored using network pharmacology and molecular docking. In in vitro studies, following TNF-α stimulation and TFST treatment, the levels of inflammatory mediators in cell culture supernatants were measured by ELISA. The subcellular localization of NF-κB p65 was detected by immunofluorescence microscopy to evaluate its nuclear translocation. In addition, Western blot analysis was performed to quantify the protein expression levels of NF-κB p65, IκBα, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin.
Results: TFST significantly normalized body weight, liver weight and liver index (P < 0.05) and improved lipid parameters (P < 0.05), while reducing plasma viscosity (P < 0.05) in GLMD rats. It also reduced hepatic lipid accumulation and injury, and enhanced the activities of rate-limiting enzymes involved in hepatic lipid metabolism (P < 0.05). In the endothelial inflammatory cell model, TFST decreased the levels of inflammatory mediators and oxidative stress (P < 0.05). Furthermore, TFST downregulated the protein expression of VCAM-1, E-selectin, and NF-κB p65, and restored IκBα levels (P < 0.05), while also suppressing NF-κB p65 nuclear translocation.
Conclusions: TFST ameliorates GLMD and vascular endothelial inflammation via NF-κB pathway inhibition.