Breast cancer promotes the expression of neurotransmitter receptor related gene groups and image simulation of prognosis model.

Breast cancer (BC), a prevalent and severe malignancy, detrimentally affects women globally. Its prognostic implications are profoundly influenced by gene expression patterns. This study retrieved 509 BCE-associated oncogenes and 1,012 neurotransmitter receptor-related genes from the GSEA and KEGG databases, intersecting to identify 98 relevant genes. Clinical and transcriptomic expression data related to BC were downloaded from the TCGA, and differential genes were identified based on an FDR value <0.05 & |log2FC| ≥ 0.585. Univariate analysis of these genes revealed that high expression of NSF and low expression of HRAS, KIF17, and RPS6KA1 are closely associated with BC survival prognosis. A prognostic model constructed for these four genes demonstrated significant prognostic relevance for BC-TCGA patients (P < 0.001). Subsequently, an immunofunctional analysis of the BC oncogene-neurotransmitter receptor-related gene cluster revealed the involvement of immune cells such as T cells CD8, T cells CD4 memory resting, and Macrophages M2. Further analysis indicated that immune functions were primarily concentrated in APC_co_inhibition, APC_co_stimulation, CCR, and Check-point, among others. Lastly, a prognostic nomogram model was established, and ROC curve analysis revealed that the nomogram is a vital indicator for assessing BC prognosis, with 1-year, 3-year, and 5-year survival rates of 0.981, 0.897, and 0.802, respectively. This model demonstrates high calibration, clinical utility, and predictive capability, promising to offer an effective preliminary tool for clinical diagnostics.

Research on the shared function of central neurons and breast cancer based on gene expression profile data mining: The role of EMID1 protein antibody expression.

In recent years, the incidence of breast cancer has gradually increased, and the research on it has become a hot spot in the scientific community. Central neurons play an important role in breast cancer. This study aims to explore the application of gene expression profile data mining in the study of shared function between central neurons and breast cancer, and focuses on the expression of EMID1 protein antibody. The study collected biomedical images and gene expression profile data of breast cancer patients. Then, we use image processing and analysis technology to extract and analyze features of biomedical images to obtain quantitative features of breast cancer. Gene expression profile data were preprocessed and analyzed to obtain information about breast cancer related genes. Integrating and fusing biomedical images and gene expression profile data, and exploring the sharing function between central neurons and breast cancer through data mining algorithms and statistical analysis methods. The results showed that the expression of EMID1 protein was high in breast cancer tissues, and the expression pattern was similar to that of central neurons. Further functional studies have shown that EMID1 protein is involved in the regulation of proliferation and invasion of breast cancer cells. By regulating the expression level of EMID1 protein, we observed that the proliferation and invasion ability of breast cancer cells were significantly affected. The research results show that through the comprehensive analysis of biomedical images and gene expression profile data, we found the sharing function between central neurons and breast cancer. The central neuronal cell marker genes EMID1 and GREB1L may be used as key biomarkers to regulate the pathogenesis of breast cancer and affect the occurrence and development of breast cancer.

Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis.

BACKGROUND: The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC. AIM: To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model. METHODS: Male rats (n = 8/each group) were randomly divided into a control (CG), a UC group (EG1), a UC + thrombin derived polypeptide 508 trifluoroacetic acid (TP508TFA; an NOS agonist) group (EG2), and a UC + NG-monomethyl-L-arginine monoacetate (L-NMMA; an NOS inhibitor) group (EG3). UC was induced by administering 5.5% DSS in drinking water without any other treatment (EG1), while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA, respectively. The disease activity index (DAI) and histological assessment were recorded for each group, whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining, Western blot, and enzyme linked immunosorbent assay, respectively. In addition, the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system. RESULTS: The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1, EG2, and EG3 than in the CG group. Compared with the EG1, the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated, respectively. Thus, during UC, regulation of the expression of NOS within the MP improved the intestinal motility, thereby favoring the recovery of intestinal functions. CONCLUSION: In UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.

Intracerebral Transplantation of Neural Stem Cells Restores Manganese-Induced Cognitive Deficits in Mice.

Manganese (Mn) is a potent neurotoxin known to cause long-lasting structural damage and progressive cognitive deficits in the brain. However, new therapeutic approaches are urgently needed since current treatments only target symptoms of Mn exposure. Recent studies have suggested a potential role for multipotent neural stem cells (NSCs) in the etiology of Mn-induced cognitive deficits. In this study, we evaluated the effect of direct intracerebral transplantation of NSCs on cognitive function of mice chronically exposed to MnCl2, and further explored the distribution of transplanted NSCs in brain tissues. NSCs were isolated and bilaterally injected into the hippocampal regions or lateral ventricles of Mn-exposed mice. The results showed that many transplanted cells migrated far away from the injection sites and survived in vivo in the Mn-exposed mouse brain, implying enhanced neurogenesis in the host brain. We found that NSCs transplanted into either the hippocampal regions or the lateral ventricles significantly improved spatial learning and memory function of the Mn-exposed mice in the Morris water maze. Immunofluorescence analyses indicated that some surviving NSCs differentiated into neurons or glial cells, which may have become functionally integrated into the impaired local circuits, providing a possible cellular basis for the improvement of cognitive function in NSC-transplanted mice. Taken together, our findings confirm the Mn-induced impairment of neurogenesis in the brain and underscore the potential of treating Mn exposure by NSC transplantation, providing a practical therapeutic strategy against this type of neurotoxicity.

Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons.

Epilepsy is a common and refractory neurological disorder, but the neuronal regulatory mechanisms of epileptogenesis remain largely unclear. Activity-dependent transcription of genes for neurotrophins such as brain-derived neurotrophic factor (BDNF) has been shown to promote epileptogenesis; however, little is known about factors that may act as intrinsic, homeostatic or counterbalancing mechanisms. Using rodent models, here we show that limbic seizure activity upregulated NRG1-ErbB4 signaling and that epileptogenesis was inhibited by infusing NRG1 intracerebrally but exacerbated by neutralizing endogenous NRG1 with soluble ErbB4 extracellular domain, by inhibiting ErbB4 activation or by deleting the Erbb4 gene. Furthermore, specific depletion of ErbB4 in parvalbumin-expressing interneurons abolished NRG1-mediated inhibition of epileptogenesis and promoted kindling progression, resulting in increased spontaneous seizures and exuberant mossy fiber sprouting. In contrast, depleting ErbB4 in CaMKIIα-positive pyramidal neurons had no effect. Thus, NRG1-induced activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve as a critical endogenous negative-feedback mechanism to suppress limbic epileptogenesis.

Conditional deletion of NRSF in forebrain neurons accelerates epileptogenesis in the kindling model.

Neuron-restrictive silencer factor (NRSF), also known as repressor element-1 silencing transcription factor, is a transcriptional repressor that plays important roles in embryonic development and neurogenesis. Recent findings show that NRSF is upregulated after seizures activity however, the link between NRSF and epileptogenesis remains poorly understood. To investigate the role of NRSF in epilepsy, we employed a Cre-loxp system to specifically delete NRSF in excitatory neurons of the postnatal mouse forebrain. In the kindling model of epileptogenesis, conditional NRSF knockout (NRSF-cKO) mice exhibited dramatically accelerated seizure progression and prolonged afterdischarge duration compared with control mice. Moreover, seizures activity-induced mossy fiber sprouting was enhanced in the NRSF-cKO mice. The degree of upregulation of Fibroblast growth factor 14 and Brain-derived neurotrophic factor (BDNF) following kainic acid-induced status epilepticus was significantly increased in the cortex of NRSF-cKO mice compared with control mice. Furthermore, the derepression of BDNF was associated by activation of PLCγ and PI(3)K signaling pathways. These findings indicate that NRSF functions as an intrinsic repressor of limbic epileptogenesis.