Search

[Display omitted] Small Ras homologous guanosine triphosphatase (Rho GTPase) family proteins are highly associated with tumorigenesis and development. As intrinsic exchange activity regulators of Rho GTPases, Rho guanine nucleotide exchange factors (RhoGEFs) have been demonstrated to be closely involved in tumor development and received increasing attention. They mainly contain two families: the diffuse B-cell lymphoma (Dbl) family and the dedicator of cytokinesis (Dock) family. More and more emphasis has been paid to the Dbl family members for their abnormally high expression in various cancers and their correlation to poor prognosis. In this review, the common and distinctive structures of Dbl family members are discussed, and their roles in cancer are summarized with a focus on Ect2, Tiam1/2, P-Rex1/2, Vav1/2/3, Trio, KALRN, and LARG. Significantly, the strategies targeting Dbl family RhoGEFs are highlighted as novel therapeutic opportunities for cancer. [ABSTRACT FROM AUTHOR]

Parkinson's disease is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. The surviving nigral dopaminergic neurons display altered spontaneous firing activity in Parkinson's disease. The firing rate of nigral dopaminergic neurons decreases long before complete neuronal death and the appearance of parkinsonian symptoms. A mild stimulation could rescue dopaminergic neurons from death and in turn play neuroprotective effects. Several neuropeptides, including cholecystokinin (CCK), ghrelin, neurotensin, orexin, tachykinins and apelin, within the substantia nigra pars compacta play important roles in the modulation of spontaneous firing activity of dopaminergic neurons and therefore involve motor control and motor disorders. Here, we review neuropeptide-induced modulation of the firing properties of nigral dopaminergic neurons. This review may provide a background to guide further investigations into the involvement of neuropeptides in movement control by modulating firing activity of nigral dopaminergic neurons in Parkinson's disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Parkinson's disease is the second most common neurodegenerative disease which is characterized by selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. The intrinsic neuronal firing activity is critical for the functional organization of brain and the specific deficits of neuronal firing activity may be associated with different brain disorders. It is known that the surviving nigra dopaminergic neurons exhibit altered firing activity, such as decreased spontaneous firing frequency, reduced number of firing neurons and increased burst firing in Parkinson's disease. Several ionic mechanisms are involved in changed firing activity of dopaminergic neurons under parkinsonian state. In this review, we summarize the changes of spontaneous firing activity as well as the possible mechanisms of nigra dopaminergic neurons in Parkinson's disease. This review may let us clearly understand the involvement of neuronal firing activity of nigra dopaminergic neurons in Parkinson's disease. • Firing property of dopaminergic neurons is associated with manifestation of PD. • The surviving dopaminergic neurons exhibit altered firing activity in PD. • Different ionic mechanisms are involved in the changes of firing activity. [ABSTRACT FROM AUTHOR]

Previous studies have shown that secretin and secretin receptors are expressed in central amygdala neurons. By using both in vivo extracellular recording as well as behavioral test, we investigated the direct electrophysiological effects of secretin in the central amygdala and its involvement in feeding behavior. Micro-pressure ejection of secretin increased the spontaneous firing rate by 104.22 ± 26.18% in 13 out of the 27 central amygdala neurons. In other 6 out of the 27 neurons, secretin decreased the firing rate by 68.80 ± 12.10%. Firing patter analysis showed that secretin did not change the firing pattern significantly. Further electrophysiological recordings revealed that secretin decreased the firing rate of glucose-sensitive neurons. In behavioral test, microinjection of secretin into the central amygdala significantly reduced cumulative food intake through cAMP-activated protein kinase activation. Based on the present electrophysiological and behavioral findings, we hypothesized that secretin may suppress food intake by its modulation of spontaneous firing of central amygdala neurons. [ABSTRACT FROM AUTHOR]

Highlights: [•] Pallidal 5-HT or 5-HT1B receptor agonist attenuated haloperidol-induced rigidity. [•] 5-HT or CP-93129 increased the spontaneous firing rate of the neurons. [•] Positive staining of 5-HT1B receptor was observed in the globus pallidus neurons. [ABSTRACT FROM AUTHOR]

Abstract: Several recent studies have revealed that statins exert anti-inflammatory effects in addition to their lipid-lowering property in vivo and in vitro. Recently, statins were shown to alleviate pain associated trauma in a neuropathic pain model. The aim of the present study was to investigate the underlying mechanisms of analgesia caused by the lipophilic statin simvastatin in an animal model of formalin-induced pain in the rat. Intrathecal pretreatment with simvastatin significantly attenuated the second phase of the acute nociceptive response to formalin injection, and daily administration of simvastatin for 7 days inhibited the long-term mechanical hyperalgesia caused by formalin injection. Spinal microglial activation (detected by Iba-1 and CD11 b immunohistochemistry and Western blot), and phosphorylated-p38 mitogen-activated protein kinase (detected by immunohistochemistry and Western blot) were significantly inhibited by simvastatin treatment at day 7 after formalin injection. In addition, peripheral formalin injection induced a significant increase in microglial RhoA activation (detected by membrane RhoA translocation ratio using Western blot) in the spinal cord. The spinal RhoA activation in microglia was reversed by simvastatin treatment. These findings suggest that simvastatin attenuates formalin-induced nociceptive behaviors, at least in part, by inhibiting microglial RhoA and p38 mitogen-activated protein kinase activation. Perspective: Our novel findings indicated that simvastatin attenuated formalin-induced nociceptive responses by inhibiting microglial RhoA and p38 mitogen-activated protein kinase activation. Inactivation of RhoA-p38 signaling pathway may be a pharmacologic target for treating microglia-directed central nervous system inflammation and chronic pain conditions. [Copyright &y& Elsevier]

Abstract: The paraventricular nucleus (PVN) of hypothalamus is a major integrative center in homeostatic control. Morphological studies have revealed a high level of secretin and secretin receptor expression in the PVN. To investigate the direct electrophysiological effects of secretin in the PVN, in vivo extracellular recordings were performed in the present study. In 24 out of the 46 paraventricular neurons, micro-pressure ejection of secretin increased the firing rate from 3.07±0.43Hz to 4.86±0.70Hz. In another 8 out of the 46 paraventricular neurons, secretin decreased the firing rate from 2.61±0.46Hz to 1.41±0.25Hz. In the remaining 14 paraventricular neurons, secretin did not alter the firing rate significantly. The present findings provided direct electrophysiological evidence for the possible functions of secretin in the PVN. [Copyright &y& Elsevier]

Abstract: Protein tyrosine phosphorylation has been implicated in normal and pathological functions such as cell proliferation, migration and differentiation. Recently, some studies have shown that Src family kinases (SFKs) were involved in neurological disorders and neuropathic pain states in which microglial activation plays a role. In the formalin test, we have reported that microglia undergo at least 2 distinct stages of activation on the basis of signaling events regarding p38 mitogen-activated protein kinases (MAPK). Here, we investigated the involvement of SFKs signaling in a formalin pain animal model and the association with p38 MAPK. Our results showed that SFKs were activated in the spinal microglia beginning 1 day after peripheral formalin injection lasting for 7 days. Pretreatment with SFK specific inhibitor PP2 could not inhibit formalin-induced spontaneous pain behaviors. However, PP2 inhibited formalin injury, induced persistent mechanical hyperalgesia, and reversed microglial phospho-p38 expression as well using immunohistostaining and Western blot at day 3 and 7 after injection. Our results suggested that the activation of the Src/p38MAPK signaling cascade in spinal microglia contributed to late stage persistent mechanical hyperalgesia evoked by formalin injection into the paw. Perspective: This study presents unique properties of spinal microglial activation in a pain animal model. This finding could potentially help clinicians to further understand the contributions of spinal microglia to acute and persistent pain state. [Copyright &y& Elsevier]

The Trotter theorem is applied to investigate the mixed-spin (1, 1/2) Heisenberg ferrimagnet chain with exchange anisotropy in a magnetic field. With the help of discretized path-integral representation and the double-chain approximation, the system is mapped onto a double chain in an effective magnetic field. We report the low temperature thermodynamics of the quantum system subject to the field. The quantized magnetization plateau as a function of the field, appearing at a third saturated magnetization, is stable over the whole antiferromagnetic coupling region. The Kosterlitz–Thouless transition point (owing to the anisotropy) is obtained in ferromagnetic coupling region αc≃−0.9. The double-peak structure in the specific heat curve is also found, which comes from the huge variation of the long-range order. [Copyright &y& Elsevier]

Abstract: There has been arguments about the estrogen receptor-α (from this point referred to as ER) of breast cancer stem cells (BrCSCs). Most investigations support the proposition that BrCSCs are ER−, whereas some other studies indicate that BrCSCs are ER+. We concluded that the ER expression of BrCSCs in ER+ breast cancers is positive, while it is negative in ER− breast cancers. Therefore, we hypothesize that the ER expression of BrCSCs depends on the original breast cancers. It may provide a novel strategy for the therapy targeting BrCSCs. [Copyright &y& Elsevier]

• The globus pallidus contains a high level of neuropeptides and endocannabinoids. • Neuropeptides and endocannabinoids modulate the neuronal activity of the globus pallidus through multiple mechanisms. • Pallidal neuropeptides and endocannabinoids are associated with the pathophysiology of neurological disorders, such as Parkinson's disease. The globus pallidus in the basal ganglia plays an important role in movement regulation. Neuropeptides and endocannabinoids are neuronal signalling molecules that influence the functions of the whole brain. Endocannabinoids, enkephalin, substance P, neurotensin, orexin, somatostatin and pituitary adenylate cyclase-activating polypeptides are richly concentrated in the globus pallidus. Neuropeptides and endocannabinoids exert excitatory or inhibitory effects in the globus pallidus mainly by modulating GABAergic, glutamatergic and dopaminergic neurotransmission, as well as many ionic mechanisms. Pallidal neuropeptides and endocannabinoids are associated with the pathophysiology of a number of neurological disorders, such as Parkinson's disease, Huntington's disease, schizophrenia, and depression. The levels of neuropeptides and endocannabinoids and their receptors in the globus pallidus change in neurological diseases. It has been demonstrated that spontaneous firing activity of globus pallidus neurons is closely related to the manifestations of Parkinson's disease. Therefore, the neuropeptides and endocannabinoids in the globus pallidus may function as potential targets for treatment in some neurological diseases. In this review, we highlight the morphology and function of neuropeptides and endocannabinoids in the globus pallidus and their involvement in neurological diseases. [ABSTRACT FROM AUTHOR]

The spontaneous firing activity of nigral dopaminergic neurons is associated with some important roles including modulation of dopamine release, expression of tyrosine hydroxylase (TH), as well as neuronal survival. The decreased neuroactivity of nigral dopaminergic neurons has been revealed in Parkinson's disease. Central glucagon-like peptide-1 (GLP-1) functions as a neurotransmitter or neuromodulator to exert multiple brain functions. Although morphological studies revealed the expression of GLP-1 receptors (GLP-1Rs) in the substantia nigra pars compacta, the possible modulation of GLP-1 on spontaneous firing activity of nigral dopaminergic neurons is unknown. The present extracellular in vivo single unit recordings revealed that GLP-1R agonist exendin-4 significantly increased the spontaneous firing rate and decreased the firing regularity of partial nigral dopaminergic neurons of adult male C57BL/6 mice. Blockade of GLP-1Rs by exendin (9–39) decreased the firing rate of nigral dopaminergic neurons suggesting the involvement of endogenous GLP-1 in the modulation of firing activity. Furthermore, the PKA and the transient receptor potential canonical (TRPC) 4/5 channels are involved in activation of GLP-1Rs-induced excitatory effects of nigral dopaminergic neurons. Under parkinsonian state, both the exogenous and endogenous GLP-1 could still induce excitatory effects on the surviving nigral dopaminergic neurons. As the mild excitatory stimuli exert neuroprotective effects on nigral dopaminergic neurons, the present GLP-1-induced excitatory effects may partially contribute to its antiparkinsonian effects. • GLP-1R agonist exendin-4 increased the firing rate of nigral dopaminergic neurons. • Endogenous GLP-1 is involved in the modulation of firing activity. • PKA and TRPC 4/5 channels are involved in GLP-1R-induced excitation. • GLP-1 is functional on the surviving nigral dopaminergic neurons in PD mice. [ABSTRACT FROM AUTHOR]

This aim of this study was to remove triethylamine by a biological method, as well as to understand the ability of mixed bacteria cultures to treat a triethylamine compound from synthetic wastewater. The mixed bacteria cultures could not remove triethylamine, whether the activated sludge came from an acrylonitrile–butadiene–styrene resin manufactured wastewater treatment system or a waterborne polyurethane resin manufactured wastewater treatment system. When the mixed bacteria cultures were acclimated to triethylamine, they could utilize 650mgl−1 triethylamine for growth. When the initial triethylamine concentration was below 200mgl−1, the triethylamine removal efficiency could reach 100%. The triethylamine removal rate of the acclimated GMIX sludge was faster than the acclimated EMIX sludge. [Copyright &y& Elsevier]

The Calcium-sensing receptor (CaSR) participates in the regulation of gastrointestinal (GI) motility under normal conditions and might be involved in the regulation of GI dysmotility in patients with Parkinson's disease (PD). CaSR antagonist-NPS-2143 was applied in in vivo and ex vivo experiments to study the effect and underlying mechanisms of CaSR inhibition on GI dysmotility in the MPTP-induced PD mouse model. Oral intake of NPS-2143 promoted GI motility in PD mice as shown by the increased gastric emptying rate and shortened whole gut transit time together with improved weight and water content in the feces of PD mice, and the lack of influence on normal mice. Meanwhile, the number of cholinergic neurons, the proportion of serotonergic neurons, as well as the levels of acetylcholine and serotonin increased, but the numbers of nitrergic and tyrosine hydroxylase immunoreactive neurons, and the levels of nitric oxide synthase and dopamine decreased in the myenteric plexus in the gastric antrum and colon of PD mice in response to NPS-2143 treatment. Furthermore, the numbers of c-fos positive neurons in the nucleus tractus solitarius (NTS) and cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) increased in NPS-2143 treated PD mice, suggesting the involvement of both the enteric (ENS) and central (CNS) nervous systems. However, ex vivo results showed that NPS-2143 directly inhibited the contractility of antral and colonic strips in PD mice via a non-ENS mediated mechanism. Further studies revealed that NPS-2143 directly inhibited the voltage gated Ca2+ channels, which might, at least in part, explain its direct inhibitory effects on the GI muscle strips. CaSR inhibition by its antagonist ameliorated GI dysmotility in PD mice via coordinated neuronal regulation by both ENS and CNS in vivo , although the direct effects of CaSR inhibition on GI muscle strips were suppressive. [Display omitted] • Oral intake of NPS-2143 promoted gastrointestinal motility. • ENS and CNS are involved in the effects of NPS-2143 in vivo. • Direct effects of NPS-2143 on gastrointestinal strips is suppressive via VGCC. [ABSTRACT FROM AUTHOR]

The dopaminergic neurons in the substantia nigra pars compacta are characterized by autonomous pacemaking activity. The spontaneous firing activity of nigral dopaminergic neurons plays an important role in physiological function and is essential for their survival. Importantly, the spontaneous firing activity may also be involved in the preferential vulnerability of the nigral dopaminergic neurons in Parkinson's disease (PD). The neuropeptide apelin was reported to exert neuroprotective effects in neurodegenerative diseases, including PD. And it was noticed that apelin modulates neuronal activity in some brain regions. The present study investigated the electrophysiological and behavioral effects of apelin in the substantia nigra. Double-labeling immunofluorescence showed that apelin was present in nigral dopaminergic neurons and that these neurons expressed apelin receptor APJ. Further single unit in vivo electrophysiological recordings revealed that endogenous apelin tonically increased the firing rate of nigral dopaminergic neurons in both normal and parkinsonian animals. Exogenous apelin-13 exerted excitatory effects on the majority of nigral dopaminergic neurons, yet reduced excitability in a subset of neurons. In addition, nigral application of apelin-13 increased motor activity in normal rats and blocking endogenous apelin reduced motor activity. Considering the involvement of the spontaneous firing activity of nigral dopaminergic neurons in the development of PD and the possibility that apelin acts in an autocrine manner on apelin receptors expressed by nigral dopaminergic neurons, the modulation of the spontaneous firing activity of nigral dopaminergic neurons by apelin may serve as a neuroprotective factor in PD. • Apelin and APJ were colocalized with TH in the nigral dopaminergic neurons. • Endogenous apelin modulated the firing activity of nigral dopaminergic neurons. • Apelin-13 bidirectionally regulated the excitability of nigral dopaminergic neurons. • Apelin in SNc enhanced motor activity of normal rats. [ABSTRACT FROM AUTHOR]

Seven undescribed meroterpenoids with different substituted types of p -menthane, named maglignans D–J (1 – 7), were obtained from the bark of Magnolia officinalis var. biloba. Maglignan D (1) was an unusual meroterpenoid, featuring two p -menthane units with different substitution types were connected to two C6C3 fragments, respectively. Maglignans E–G (2 – 4) were characterized by a 6/5/6 or 6/6/6 tricyclic skeleton. The p -menthane in others connected to the magnolol through the ether or carbon-carbon single bonds directly. Spectroscopic techniques, NMR calculations with DP4+ analysis, and ECD calculations were used for the structure elucidation of these compounds. Moreover, maglignan E (2) showed significant neuroprotective effects on glutamic acid-induced cellular damage in cortical and hippocampal neurons. [Display omitted] • Seven undescribed p -menthane-based meroterpenoids were isolated from the bark of Magnolia officinalis var. biloba. • Maglignan D (1) was an unusual meroterpenoids possessing two different types of p -menthane. • The structures were determined by spectroscopic techniques and theoretical calculations. • Maglignan E (2) showed neuroprotective effect on glutamic acid-induced cellular damage in cortical and hippocampal neurons. [ABSTRACT FROM AUTHOR]

We investigate wave-vector filtering and spin filtering for electrons tunneling through a magnetic double-barrier and double-well quantum structure in the presence of an external electric field, where the double magnetic wells are within or outside the double magnetic barriers. It is shown that electronic resonant tunneling shows strong wave-vector-dependent enhancement and suppression as the applied bias increases. It is also shown that although the current density decreases with the strength of the inhomogeneous magnetic field increasing, the degree of spin polarization is generally enhanced and shows a more wider and nearly 100% spin polarization plateau in small external bias range. The general rules for relations between wave-vector filtering and the magnetic configuration as well as between spin filtering and the magnetic configuration are summarized and explained. [Copyright &y& Elsevier]