PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

Correlation between Nurr1 expression and drug resistance in the brain of rats with epilepsy.

OBJECTIVE: To investigate the correlation between nuclear receptor related 1 (Nurr1) expression and drug resistance in the brain of rats with epilepsy. MATERIALS AND METHODS: A total of 60 adult male Sprague-Dawley rats were selected, and the animal model of epilepsy was established by electrical stimulation. These rats were randomly divided into the control group and the drug-resistant group. The model of drug-resistant epilepsy was screened with phenytoin (PHT) and phenobarbital (PB); the hippocampus and temporal lobe cortex tissues were isolated from rats; the messenger ribonucleic acid (mRNA) and protein levels of Nurr1 in the hippocampus and cortex tissues of the two groups of rats were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry, respectively. The budding tissue marker growth-associated protein-43 (GAP43) in hippocampus tissues were labeled by immunofluorescence staining; the mRNA and protein levels of indicators related to drug-resistant epilepsy, including leukemia-associated phenotype (LAP), multi-drug resistance protein (MRP), P-glycoprotein (P-gp) and monocyte chemoattractant protein-1 (MCP-1), were further detected. Pearson correlation analysis was used to analyze the correlations of the protein level of Nurr1 with drug-resistant indicators. RESULTS: The mRNA and protein levels of Nurr1 in hippocampus tissues of the drug-resistant group were significantly increased compared with those of the control group (p < 0.05). In temporal lobe cortex tissues, there was no significant difference in the mRNA level of Nurr1 between the control group and the drug-resistant group (p > 0.05). The immunohistochemistry results showed that the fluorescence intensity of GAP3 in hippocampus tissues of the drug-resistant group was significantly higher than that of the control group. The mRNA and protein levels of epilepsy-related indicators, LAP, MRP, P-gp and MCP-1 in hippocampus tissues of drug-resistant group were significantly up-regulated compared with those of the control group (p < 0.05). Pearson correlation analysis indicated that the protein level of Nurr1 in hippocampus tissues was positively correlated with those of LAP, MRP, P-gp and MCP-1 in the corresponding regions (p < 0.05). CONCLUSIONS: Nurr1 enhances the drug resistance of epilepsy in rats by up-regulating the expression of proteins related to drug resistance.

Human periapical cyst-mesenchymal stem cells differentiate into neuronal cells.

It was recently reported that human periapical cysts (hPCys), a commonly occurring odontogenic cystic lesion of inflammatory origin, contain mesenchymal stem cells (MSCs) with the capacity for self-renewal and multilineage differentiation. In this study, periapical inflammatory cysts were compared with dental pulp to determine whether this tissue may be an alternative accessible tissue source of MSCs that retain the potential for neurogenic differentiation. Flow cytometry and immunofluorescence analysis indicated that hPCy-MSCs and dental pulp stem cells spontaneously expressed the neuron-specific protein ß-III tubulin and the neural stem-/astrocyte-specific protein glial fibrillary acidic protein (GFAP) in their basal state before differentiation occurs. Furthermore, undifferentiated hPCy-MSCs showed a higher expression of transcripts for neuronal markers (ß-III tubulin, NF-M, MAP2) and neural-related transcription factors (MSX-1, Foxa2, En-1) as compared with dental pulp stem cells. After exposure to neurogenic differentiation conditions (neural media containing epidermal growth factor [EGF], basic fibroblast growth factor [bFGF], and retinoic acid), the hPCy-MSCs showed enhanced expression of ß-III tubulin and GFAP proteins, as well as increased expression of neurofilaments medium, neurofilaments heavy, and neuron-specific enolase at the transcript level. In addition, neurally differentiated hPCy-MSCs showed upregulated expression of the neural transcription factors Pitx3, Foxa2, Nurr1, and the dopamine-related genes tyrosine hydroxylase and dopamine transporter. The present study demonstrated for the first time that hPCy-MSCs have a predisposition toward the neural phenotype that is increased when exposed to neural differentiation cues, based on upregulation of a comprehensive set of proteins and genes that define neuronal cells. In conclusion, these results provide evidence that hPCy-MSCs might be another optimal source of neural/glial cells for cell-based therapies to treat neurologic diseases.