Slow synaptic excitation (slow EPSP) in enteric neurones is recorded as a slowly activating depolarization of the membrane potential in specific populations of enteric neurones when neurotransmitters are released experimentally by focal electrical stimulation of presynaptic axons in the myenteric and submucosal plexuses (reviewed by Surprenant, 1989;Wood, 1994;Galligan, 1998;Gershon, 1998). Mediators released to the enteric nervous system in paracrine fashion from non-neuronal cell types (e.g. histamine and cytokines from enteric mast cells) can evoke responses that mimic slow synaptic excitation (Wood, 1992;Liu et al. 2003). Two kinds of slow EPSPs are recorded in enteric neurones. An increase in input resistance is associated with the depolarization and augmented excitability for one kind of slow EPSP. The input resistance decreases or remains unchanged during the depolarization and augmented excitability of the second kind. Slow EPSPs with increased input resistance are found generally in AH-type neurones with multipolar Dogiel Type II morphology. Most evidence suggests that the principal ionic mechanism for this type of slow EPSP is suppression of resting Ca 2+ -dependent K + conductance that accounts for the membrane depolarization, increased input resistance, and suppression of the Ca 2+ component of the rising phase of the action potential (e.g. Grafe et al. 1980). Signal transduction for the slow EPSP with increased input resistance involves coupling of metabotropic receptors through heterotrimeric G proteins to adenylate cyclase, and elevation of intraneuronal cyclic adenosine monophosphate (Palmer et al. 1986(Palmer et al. , 1987.Whereas slow EPSPs characterized by increased input resistance during the depolarizing response predominate in AH-type neurones in the myenteric plexus, slow EPSPs characterized by decreased input resistance are routinely found in S-type uniaxonal neurones in the small and large intestinal submucosal plexus. Likewise, application of putative neurotransmitters and paracrine mediators (e.g. serotonin, ATP and substance P) evoke slowly activating depolarizing responses associated with decreased input resistance in S-type neurones in the submucosal plexus.This report presents evidence that synaptically released ATP acts at P2Y 1 purinergic receptors to evoke slow EPSPs that are characterized by decreased input resistance in the submucosal plexus. The evidence suggests that the signal transduction cascade for the submucosal P2Y 1 receptor includes activation of phospholipase C, release of inositol 1,4,5-trisphosphate and elevation of cytosolic free Ca

The development and application of whole genome sequencing technology has greatly broadened our horizons on the capabilities of long non-coding RNAs (lncRNAs). LncRNAs are more than 200 nucleotides in length and lack protein-coding potential. Increasing evidence indicates that lncRNAs exert an irreplaceable role in tumor initiation, progression, as well as metastasis, and are novel molecular biomarkers for diagnosis and prognosis of cancer patients. Furthermore, lncRNAs and the pathways they influence might represent promising therapeutic targets for a number of tumors. Here, we discuss the recent advances in understanding of the specific regulatory mechanisms of lncRNAs. We focused on the signal, decoy, guide, and scaffold functions of lncRNAs at the epigenetic, transcription, and post-transcription levels in cancer cells. Additionally, we summarize the research strategies used to investigate the roles of lncRNAs in tumors, including lncRNAs screening, lncRNAs characteristic analyses, functional studies, and molecular mechanisms of lncRNAs. This review will provide a short but comprehensive description of the lncRNA functions in tumor development and progression, thus accelerating the clinical implementation of lncRNAs as tumor biomarkers and therapeutic targets.

Transient receptor potential vanilloid (TRPV) channels are polymodal detectors of multiple environmental factors, including temperature, pH, and pressure. Inflammatory mediators enhance TRPV function through multiple signaling pathways. The lipoxygenase and epoxygenase products of arachidonic acid (AA) metabolism have been shown to directly activate TRPV1 and TRPV4, respectively. TRPV3 is a thermosensitive channel with an intermediate temperature threshold of 31-39 degrees C. We have previously shown that TRPV3 is activated by 2-aminoethoxydiphenyl borate (2APB). Here we show that AA and other unsaturated fatty acids directly potentiate 2APB-induced responses of TRPV3 expressed in HEK293 cells, Xenopus oocytes, and mouse keratinocytes. The AA-induced potentiation is observed in intracellular Ca2+ measurement, whole-cell and two-electrode voltage clamp studies, as well as single channel recordings of excised inside-out and outside-out patches. The fatty acid-induced potentiation is not blocked by inhibitors of protein kinase C and thus differs from that induced by the kinase. The potentiation does not require AA metabolism but is rather mimicked by non-metabolizable analogs of AA. These results suggest a novel mechanism regulating the TRPV3 response to inflammation, which differs from TRPV1 and TRPV4, and involves a direct action of free fatty acids on the channel.

Hu proteins, together with neurone-specific enolase (NSE), protein gene product 9.5 (PGP-9.5), microtubule-associated protein-2 (MAP-2) and tubulin beta III isoform, were evaluated immunohistochemically as neuronal markers in whole-mount preparations and cultures obtained from the myenteric plexus of guinea-pig small intestine. Anti-Hu immunostaining marked the ganglion cell somas and nuclei without staining of the neuronal processes in the whole-mounts and cultures. The ganglion cell bodies were not obscured by staining of multiple neuronal fibres and this facilitated accurate counting of the neurones. MAP2 immunostaining also provided clear images of individual neurones in both whole mounts and cultures. Immunoreactivity for NSE, PGP-9.5 and tubulin beta III isoform provided sharp images of the ganglion cells in culture, but not in whole-mount preparations. Strong staining of the neuronal processes in the whole-mount preparations obscured the profiles of the ganglion cell bodies to such an extent that accurate counting of the total neuronal population was compromised. Anti-Hu immunostaining was judged to be an acceptable method for obtaining reliable estimates of total numbers of myenteric neurones in relation to other specific histochemical properties such as histamine binding.

Increased levels of IL-17-producing Tregs were identified in RA patients. This Treg subset with Th17 plasticity in peripheral blood retained suppressive functions and was associated with milder inflammatory conditions, suggesting that this Treg population works as a negative regulator in RA, but in RA synovial site it may be pathogenic.