PM_2.5 is fine particulate matter with a diameter of less than 2.5 μm. Recent evidence has shown that exposure to PM_2.5 markedly elevates the risk of neurodegenerative diseases, neurodevelopmental disorders, and cardiovascular diseases, which may culminate in cognitive impairment. Nevertheless, the precise mechanisms through which PM_2.5 affects cognitive function are unclear. Recent studies have demonstrated that PM_2.5-induced epigenetic alterations are associated with the development of cognitive impairment. Epigenetic alterations include modifications to DNA methylation, histone modifications, and non-coding RNAs. The underlying mechanisms of epigenetic alterations are related to inflammation, synaptic dysfunction, cardiovascular factors, and alterations in neuronal structure and function. This review reports the latest findings on the relationship between PM_2.5-induced epigenetic alterations and the development of cognitive disorders, offering novel insights into the cognitive effects of air pollution.

This study identified a transcription factor that might bind to the 5′ regulatory region of the HTR1A and explored the potential effect on 5-HT1A receptor expression. Based on JASPAR predictions, the binding of the transcription factor was demonstrated using the electrophoretic mobility shift assay (EMSA). Vectors over-expressing the transcription factor were co-transfected into HEK-293 and SK-N-SH cells with the recombinant pGL3 vector, and relative fluorescence intensity was measured to determine regulatory activity. Additionally, the qRT-PCR and Western blot were also used to identify whether the transcription factor modulated the endogenous expression of 5-HT1A receptor. The results suggest that the transcription factor CCAA/T enhancer binding protein beta (CEBPB) likely binds to the −1219 to −1209 bp (ATG+1) region of the HTR1A. Two sequences located in the −722 to −372 bp and −119 to +99 bp were also identified. Although the effect of CEBPB on endogenous 5-HT1A receptor expression was not significant, it exhibited the strong inhibition on the relative fluorescence intensity and the mRNA level of HTR1A. CEBPB inhibited the human HTR1A expression by binding to the sequence −1219–−1209 bp. This is useful and informative for ascertaining the regulation of 5-HT1A receptor and mental diseases.

Abnormal expression of ionotropic glutamate receptor NMDA type subunit 1, the key subunit of the NMDA receptor, may be related to many neuropsychiatric disorders. In this study, we explored the functional sequence of the 5' regulatory region of the human GRIN1 gene and discussed the transcription factors that may regulate gene expression. Twelve recombinant pGL3 vectors with gradually truncated fragment lengths were constructed, transfected into HEK-293, U87, and SK-N-SH cell lines, and analyzed through the luciferase reporter gene assay. JASPAR database is used to predict transcription factors. In SK-N-SH and U87 cell lines, regions from -337 to -159 bp, -704 to -556 bp inhibited gene expression, while -556 to -337 bp upregulated gene expression. In HEK-293 and U87 cell lines, the expression of fragment -1703 to + 188 bp was significantly increased compared to adjacent fragments -1539 to + 188 bp and -1843 to + 188 bp. The protein expressions of fragments -2162 to + 188 bp and -2025 to + 188 bp, -1539 to + 188 bp and -1215 to + 188 bp, -1215 to + 188 bp and -1066 to + 188 bp were significantly different in HEK-293 and SK-N-SH cells. According to the predictions of the JASPAR database, the transcription factors REST, EGR1, and CREB1/HIC2 may bind the DNA sequences of GRIN1 gene from the -337 to -159, -556 to -337, and -704 to -556, respectively. In addition, zinc finger transcription factors may regulate the expression of other differentially expressed fragments. Abnormal transcription regulation in the proximal promoter region of GRIN1 (-704 to + 188 bp) may be involved in the course of neuropsychiatric diseases.

Background: Umbralisib, a dual PI3Kδ/CK-1ϵ inhibitor, has shown clinical activity in various hematologic malignancies. However, a systematic assessment of its efficacy and safety is still lacking. This study provides a comprehensive evaluation based on current clinical evidence. Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, CNKI, and ClinicalTrials.gov for studies involving umbralisib in hematologic malignancies (up to March 14, 2025). Two investigators independently screened eligible studies and extracted data. Efficacy outcomes and adverse events (AEs) were analyzed using meta-analytic methods. The review protocol was registered in PROSPERO (registration number: CRD420251018098). Results: Umbralisib monotherapy was associated with frequent hematologic AEs such as thrombocytopenia, neutropenia, and anemia, along with common non-hematologic toxicities including diarrhea, nausea, and fatigue. Liver enzyme elevation and diarrhea represented the more severe AEs. Combination therapy showed a distinct AE profile, with infusion reactions and infections being more prominent, but generally demonstrated fewer severe toxicities. In terms of efficacy, monotherapy yielded a modest objective response rate, while combination regimens achieved substantially higher response rates, including improved complete and partial response outcomes. Conclusion: Umbralisib shows promising efficacy in hematologic malignancies such as MZL, FL, and DLBCL, though its clinical use is limited by frequent AEs. Combination therapy offers better response rates and appears to alleviate some of the severe toxicities seen with monotherapy. Further studies are needed to optimize combination strategies, explore alternative administration routes, and refine dosing approaches. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251018098.

Background: Inflammatory processes play a critical role in ischaemic stroke. Acetylation of NLRP3 is a key step in amplifying neuroinflammation. (LbGP), a bioactive glycoprotein derived from Lycium barbarum, has anti-inflammatory potential, but its mechanisms in post-stroke neuroinflammation remain unclear. Aim: This study aimed to investigate the efficacy and molecular mechanisms of LbGP in alleviating neuroinflammation following ischaemic stroke. Methods: A mouse model of middle cerebral artery occlusion (MCAO)/reperfusion was used to induce focal cerebral ischaemia/reperfusion (I/R) injury. Microglial cells were subjected to oxygen-glucose deprivation/reoxygenation. Neurological recovery was assessed by Y-maze and open-field tests. Molecular mechanisms were explored using Western blotting, ELISA, co-immunoprecipitation and immunofluorescence. Results: LbGP significantly reduced cerebral infarct volume, attenuated neuroinflammation and improved functional recovery in I/R mice. Mechanistically, LbGP suppressed NLRP3 inflammasome activation through Sirtuin 3-mediated inhibition of NLRP3 acetylation, a finding further validated by exacerbated neuroinflammation in Sirt3-knockout mice. Conclusion: This study demonstrates for the first time that LbGP alleviates post-stroke neuroinflammation via Sirt3-mediated deacetylation of NLRP3, thereby disrupting inflammasome activation, and identifies LbGP as a promising therapeutic candidate for ischaemic stroke.