In the central auditory system, cartwheel cells (CWCs) are a group of interneurons in the dorsal cochlear nucleus (DCN). While other DCN neurons respond to stimuli with a simple discharge pattern of single action potentials (SAPs), CWCs respond with complex action potentials (CAPs), consisting of SAPs superimposed on a slow depolarization. The CAPs in CWCs may participate in various auditory or non‑auditory signaling processing but its intrinsic mechanisms are largely unknown. In the present study, in vitro whole‑cell current clamp recordings on neonatal mice brain slices were used to demonstrate that CWCs respond to brief voltage stimulation with CAPs. Western blotting and immunohistochemistry were also utilized to demonstrate that Nav1.9 was expressed in the CWCs. Finally, when Nav1.9 was genetically silenced, CWCs responded to voltage stimulation with SAPs, not CAPs. The results strongly suggested that Nav1.9 was expressed and functionally contributed to the signaling processing in the central auditory pathway.
Tuberculosis (TB) is an ancient disease caused by Mycobacterium tuberculosis (Mtb). TB is one of the world's deadliest diseases, with one-third of infected individuals falling ill each year especially in many developing countries. Upon invading host cells, such as macrophages, Mtb can replicate in infected cells by arresting phagosome maturation and then potentially escaping into the cytosol. Host cells have a mechanism to control intracellular Mtb by inducing autophagy, which is an elaborate cellular process to target intracellular pathogens for degradation in infected cells. However, some factors of Mtb are involved in defense against killing by autophagy. Thus, this review highlights the recent advances in the interactions between autophagy and Mtb.
e14651 Background: Early lymph node metastasis is one of the most important characteristic features of pancreatic ductal adenocarcinoma (PDAC) with a dismal prognosis. MicroRNAs (miRNAs) have been shown to have a role in oncogenesis, invasion, and metastasis via epigenetic posttranscriptional gene regulation. However lymphatic metastasis related miRNAs of pancreatic cancer (PC) has not been well documented. Methods: Through microarray analysis aberrantly expressing miRNAs potentially regulating lymphatic metastasis in PC were gained from PDAC tissue specimens and cell lines. Candidate miRNAs were confirmed in total 40 resected PDAC cases and cell lines by quantitative reverse transcription-PCR (qRT-PCR). In situ hybridization was performed to elucidate the expression features of miRNA-218 in PDAC, precursor lesions, metastatic lymph nodes and cell lines. Results: MiRNA-218 and other five miRNAs were found aberrantly expressing both in PDAC and BxPC-3-LN5 (cell line with high-metastasis characteristics) by microarray analysis. Down-regulated expression of miRNA-218 was validated in PDAC tissue samples (4 fold decrease) compared to adjacent benign tissue (p=0.006) and cell line BxPC-3-LN5 (3 fold decrease) compared to BxPC-3 (p=0.01). Clinicopathological data demonstrated inverse correlation of miRNA-218 expression with lymph node metastasis (p=0.045). Expression of miRNA-218 was down-regulated in IPMN and even decreased in PDAC in a grade-dependent manner. Almost negative expression of miRNA-218 was revealed in metastatic lymph nodes. Conclusions: Down-regulated expression of miRNA-218 in PDAC and its expression features in precursor lesions suggests a tumor suppressor action of miRNA-218 in PDAC. Decreased expression of miRNA-218 may be associated with lymphatic metastasis of PDAC and interpret the high-metastasis ability of BxPC-3-LN5 cell line.
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