LINC01198 promotes proliferation and temozolomide resistance in a NEDD4-1-dependent manner, repressing PTEN expression in glioma.

BACKGROUND: Dysregulation of numerous lncRNAs has been recently confirmed in glioma; however, the majority of their roles and mechanisms involved in this notorious disease remain largely unclear. This study aims to explore the roles and molecular mechanisms of LINC01198 implicated in the proliferation and chemoresistance in glioma. RESULTS: LINC01198 was elevated in glioma, and this predicted a poorer prognosis for patients with glioma. LINC01198 knockdown inhibited, while LINC01198 overexpression promoted, glioma cell proliferation and resistance to temozolomide. Mechanistically, NEDD4-1 (neural precursor cell expressed, developmentally downregulated 4, E3 ubiquitin protein ligase) and phosphatase and tensin homolog (PTEN) were recruited by LINC01198, which functioned as a scaffold. Moreover, we showed that LINC01198 exerted its oncogenic activities by enhancing the NEDD4-1-dependent repression of PTEN. CONCLUSIONS: Our study elucidated the role of oncogenic LINC01198 in glioma proliferation and temozolomide resistance, and this role may serve as a promising target for glioma therapy. METHODS: LINC01198 expression in glioma tissues and that in paired normal tissues were measured by qRT-PCR. The functional roles of LINC01198 in glioma were demonstrated by a series of in vitro experiments. CCK-8 assay, RNA pulldown, RNA immunoprecipitation and western blotting were used to demonstrate the potential mechanisms of LINC01198.

Psora-4, a Kv1.3 Blocker, Enhances Differentiation and Maturation in Neural Progenitor Cells.

AIM: The self-repair ability of neural progenitor cells (NPCs) has been found to be activated and protected in several therapies helpful in multiple sclerosis (MS), an inflammatory demyelinating disease of the CNS. As a potential therapeutic target in MS, the role of the ion channel Kv1.3 in NPC self-repair has received limited attention. The aim of this study was to explore the effects of a selective Kv1.3 blocker on NPC neuronal differentiation and maturation. METHODS: A small-molecule selective blocker for Kv1.3, Psora-4, was added to the differentiation medium of cultured mouse NPCs to assess its effect on NPC differentiation efficiency. Both a polypeptide Kv1.3 blocker and Kv1.3-specific RNA interference were used in parallel experiments. Further, the maturity of newborn neurons in the presence of Psora-4 was measured both by morphological analysis and by whole-cell patch clamping. RESULTS: Psora-4 induced a significant increase in the percentage of neurons. Knockdown of Kv1.3 in NPCs also promoted neuronal differentiation. Both morphological and electrophysiological analyses suggested that NPC-derived neurons in the presence of Psora-4 were more mature. CONCLUSION: Our studies reveal a crucial role for the ion channel Kv1.3 in the regulation of NPC differentiation and maturation, making Psora-4 a promising candidate molecule for MS treatment.

Usefulness of dual-energy computed tomography imaging in the differential diagnosis of sellar meningiomas and pituitary adenomas: preliminary report.

OBJECTIVE: To quantitatively assess the imaging characteristics of sellar lesion in dual-energy computed tomography (CT) imaging for differentiation of sellar meningiomas and pituitary adenomas during the arterial phase (AP) and venous phase (VP). MATERIALS AND METHODS: 51 patients with sellar/parasellar tumors (33 macroadenomas and 18 meningiomas) were examined with CT spectral imaging during the AP and the VP. Iodine concentrations were derived from iodine-based material-decomposition CT images and normalized to the iodine concentration in the aorta. The difference in Normalized iodine concentrations (NICs), HU curve slope (λHU), and mean CT values of lesions between the AP and VP were calculated. The two-sample t test was performed to compare quantitative parameters between sellar meningiomas and pituitary adenomas. RESULTS: NICs, λHU, and mean CT values in patients with sellar meningiomas differed significantly from those in patients with pituitary adenomas: Mean NICs were 43.52 mg/mL±1.35 versus 9.23 mg/mL ±2.44, respectively, during the AP and 52.13 mg/mL ±1.04 versus 24.37 mg/mL ±2.23 respectively, during the VP. λHU were -3.03±3.42 versus -0.53±0.23, respectively, during the AP and -2.96±0.41 versus -0.47±0.25, respectively, during the VP. Mean CT values were 193.63±2.08 versus 63.98±2.85, respectively, during the AP and 203.98±0.18 versus 77.66±0.91, respectively, during the VP. The combination of NIC and Mean CT value during VP had highest sensitivity (90.9%) and specificity (100%) among all phases. CONCLUSION: Quantitative dual-energy CT imaging has promising potential for diagnostic differentiation of sellar meningiomas and pituitary adenomas.

The gain modulation by N-methyl-D-aspartate in the projection neurons of robust nucleus of the arcopallium in adult zebra finches.

The song of zebra finch is stable in life after it was learned successfully. Vocal plasticity is thought to be a motor exploration that can support continuous learning and optimization of performance. The activity of RA, an important pre-motor nucleus in songbird's brain, influences the song directly. This variability in adult birdsong is associated with the activity of NMDA receptors in LMAN-RA synapses, but the detailed mechanism is unclear. The control of gain refers to modulation of a neuron's responsiveness to input and is critically important for normal sensory, cognitive, and motor functions. Here, we observed the change of gain in RA projection neurons after exogenous NMDA was applied to activate NMDA receptors using the whole-cell current clamp recording. We found that NMDA substantially increased the slope (gain) of the firing rate-current relationship in RA projection neurons. The AMPA receptor-dependent excitability played a crucial role in the modulation of gain by NMDA. These results suggested that NMDA receptors may regulate the dynamics of RA projection neurons by input-output gain.

SK channels modulate the excitability and firing precision of projection neurons in the robust nucleus of the arcopallium in adult male zebra finches.

OBJECTIVE: Motor control is encoded by neuronal activity. Small conductance Ca(2+)-activated K(+) channels (SK channels) maintain the regularity and precision of firing by contributing to the afterhyperpolarization (AHP) of the action potential in mammals. However, it is not clear how SK channels regulate the output of the vocal motor system in songbirds. The premotor robust nucleus of the arcopallium (RA) in the zebra finch is responsible for the output of song information. The temporal pattern of spike bursts in RA projection neurons is associated with the timing of the acoustic features of birdsong. METHODS: The firing properties of RA projection neurons were analyzed using patch clamp whole-cell and cell-attached recording techniques. RESULTS: SK channel blockade by apamin decreased the AHP amplitude and increased the evoked firing rate in RA projection neurons. It also caused reductions in the regularity and precision of firing. RA projection neurons displayed regular spontaneous action potentials, while apamin caused irregular spontaneous firing but had no effect on the firing rate. In the absence of synaptic inputs, RA projection neurons still had spontaneous firing, and apamin had an evident effect on the firing rate, but caused no significant change in the firing regularity, compared with apamin application in the presence of synaptic inputs. CONCLUSION: SK channels contribute to the maintenance of firing regularity in RA projection neurons which requires synaptic activity, and consequently ensures the precision of song encoding.

Electrophysiological properties of neurons in the robust nucleus of the arcopallium of adult male zebra finches.

Nucleus robust arcopallium (RA) of the songbird is a distinct forebrain region that is essential for song production. To explore the electrophysiological properties, whole cell recordings were made from adult zebra finch RA neurons in slice preparations. Based on the electrophysiological properties, neurons in RA were classified into two distinct classes. Type I neurons were spontaneously active. They had larger input resistance, longer time constant, larger time-peak of an afterhyperpolarization (AHP), and broader action potentials than those of the other class. A slow, time-dependent inward rectification was induced by hyperpolarizing current pulses in this type of neuron, and was blocked by external CsCl (2mM). Type II neurons had a more negative resting membrane potential than that of type I neurons. They were characterized by a steeper slope of the recovery from the peak of the AHP and frequency-current relationships, a higher firing threshold, and irregular spiking in response to depolarizing current injection.

Sexual dimorphism of the electrophysiological properties of the projection neurons in the robust nucleus of the arcopallium in adult zebra finches.

OBJECTIVE: To observe the sexual differences in electrophysiological properties of neurons in the robust nucleus of the arcopallium (RA) in adult zebra finches, and to provide the direct electrophysiological evidence for the sexual dimorphism of birdsong. METHODS: Whole-cell recording was used to record the spontaneous action potential firing rates from RA projection neurons in acute brain slices. RESULTS: The projection neurons of RA in male birds fired spontaneously at 10 Hz or above, while in female birds, the frequency was significantly lower, and even no firings could be detected. CONCLUSION: There is a sexual difference in electrophysiological properties of projection neurons in RA, which may result from the difference in the levels of steroid hormones in birds.

[Screening of environmental response genes related to dental fluorosis].

OBJECTIVE: To screen environmental response genes related to dental fluorosis, and to provide clues for further researches of the molecular mechanism of fluorosis. METHODS: The leukocyte gene expression profiles of control group, high-loaded fluoride group and dental fluorosis group were tested using the gene chiR HG-U133A from Affymetrix company. The results were analyzed by bioinformatical methods. RESULTS: Compared with control group, a total of 1057 genes were differentially expressed in high-loaded fluoride group. Of these, 148 were robustly up-regulated and 61 were robustly down-regulated. A total of 964 genes were differentially expressed in dental fluorosis group as compared with control group, including 71 robustly up-regulated genes and 60 robustly down-regulated genes. Compared with high-loaded fluoride group, 633 genes were identified to be differentially expressed in dental fluorosis group. Of these, the number of robustly up-regulated genes and robustly down-regulated genes were respectively 15 and 67. CONCLUSION: Multiple genes are related to fluorosis.