Lysophosphatidylcholine trigger myocardial injury in diabetic cardiomyopathy via the TLR4/ZNF480/AP-1/NF-kB pathway.

Background: Diabetic cardiomyopathy (DC), a frequent complication of type 2 diabetes mellitus (T2DM), is mainly associated with severe adverse outcomes. Previous research has highlighted the role of Lysophosphatidylcholine (LPC) in inducing myocardial injury; however, the specific mechanisms through which LPC mediate such injury in DC remain elusive. The existing knowledge gap underscores the need for additional clarification. Consequently, this study aimed to explore the impact and underlying mechanisms of LPC on myocardial injury in DC. Methods: A total of 55 patients diagnosed with T2DM and 62 healthy controls were involved. A combination of 16s rRNA sequencing, metabolomic analysis, transcriptomic RNA-sequencing (RNA-seq), and whole exome sequencing (WES) was performed on fecal and peripheral blood samples collected from the participants. Following this, correlation analysis was carried out, and the results were further validated through the mouse model of T2DM. Results: Four LPC variants distinguishing T2DM patients from healthy controls were identified, all of which were upregulated in T2DM patients. Specifically, Lysopc (16:0, 2 N isoform) and LPC (16:0) exhibited a positive correlation with nuclear factor kappa B subunit 2 (NFKB2) and a negative correlation with Zinc finger protein 480 (ZNF480) Furthermore, the expression levels of Toll-like receptor 4 (TLR4), c-Jun, c-Fos, and NFKB2 were upregulated in the peripheral blood of T2DM patients and in the myocardial tissue of T2DM mice, whereas ZNF480 expression level was downregulated. Lastly, myocardial injury was identified in T2DM mice. Conclusions: The results indicated that LPC could induce myocardial injury in DC through the TLR4/ZNF480/AP-1/NF-kB pathway, providing a precise target for the clinical diagnosis and treatment of DC.

ZNF480 influences the prognosis, pathogenesis, and immune microenvironment in patients with lower-grade glioma.

ZNF480 has not yet attracted attention in the study of malignant tumors. Therefore, this study attempts to explain the significance of ZNF480 in the pathological process of lower-grade gliomas (LGG) based on large-scale samples from public database sources and in vitro experiments. Reverse transcription quantitative real-time polymerase chain reaction and immunohistochemistry confirmed that ZNF480 was highly expressed at both the mRNA and protein levels in LGG. Prognostic correlation analysis confirmed that the high expression of ZNF480, as an independent pathogenic gene, significantly correlates with poor survival in patients. Furthermore, the expression level of ZNF480 was significantly inhibited in SHG-44 cells treated with ademetionine disulfate tosylate. Gene set enrichment analysis showed that ZNF480 exists in multiple tumor-related signaling pathways, including the Notch signaling pathway. Immunological correlation analysis showed that ZNF480 can promote the LGG microenvironment to a high immune state and significantly enhance the infiltration of various immune cells, such as M2 macrophages. Finally, Spearman analysis showed a positive correlation of ZNF480 with many immune checkpoints, such as PD-L1. Overall, this study reveals for the first time the adverse effects of ZNF480 on the prognosis of tumor patients, which expands our understanding of the molecular mechanisms behind the regulation of ZNF480. We believe that the high expression of ZNF480 in LGG may be valuable for molecular targeted therapy or combined immunotherapy.

Whole Genome Sequencing of a Vietnamese Family from a Dioxin Contamination Hotspot Reveals Novel Variants in the Son with Undiagnosed Intellectual Disability.

Although it has been a half-century since dioxin-contaminated herbicides were used to defoliate the landscape during the Vietnam War, dioxin contamination "hotspots" still remain in Vietnam. Environmental and health impacts of these hotspots need to be evaluated. Intellectual disability (ID) is one of the diseases found in the children of people exposed to the herbicides. This study aims to identify genetic alterations of a patient whose family lived in a dioxin hotspot. The patient's father had a highly elevated dioxin concentration. He was affected with undiagnosed moderate ID. To analyze de novo mutations and genetic variations, and to identify causal gene(s) for ID, we performed whole genome sequencing (WGS) of the proband and his parents. Two de novo missense mutations were detected, each one in ETS2 and ZNF408 genes, respectively. Compound heterozygosity was identified in CENPF and TTN genes. Existing knowledge on the genes and bioinformatics analyses suggest that EST2, ZNF408, and CENPF might be promising candidates for ID causative genes.