Photoreceptors are non-spiking neurons, and their synapses mediate the continuous release of neurotransmitters under the control of L-type voltage-gated calcium channels (VGCCs). Photoreceptors express endogenous circadian oscillators that play important roles in regulating photoreceptor physiology and function. Here, we report that the L-type VGCCs in chick cone photoreceptors are under circadian control. The L-type VGCC currents are greater when measured during the subjective night than during the subjective day. Using antibodies against the VGCCa1C and VGCCa1D subunits, we found that the immunofluorescence intensities of both VGCCa1C and VGCCa1D in photoreceptors are higher during the subjective night. However, the mRNA levels of VGCCa1D, but not VGCCa1C, are rhythmic. Nocturnal increases in L-type VGCCs are blocked by manumycin A, PD98059, and KN93, which suggest that the circadian output pathway includes Ras, Erk, and calcium-calmodulin dependent kinase II. In summary, four independent lines of evidence show that the L-VGCCs in cone photoreceptors are under circadian control. Keywords: avian, circadian, photoreceptor, retina, voltagegated calcium channel. Visual systems must anticipate daily changes in ambient illumination over 10-12 orders of magnitude. Circadian oscillators in the retina provide a mechanism for visual systems to initiate more sustained adaptive changes throughout the course of the day (Cahill and Besharse 1995;Green and Besharse 2004). The circadian oscillators in photoreceptors are endogenous and able to function independently in the absence of other retinal inputs (Cahill and Besharse 1993;Thomas et al. 1993;Ko et al. 2001). Photoreceptor circadian oscillators regulate retinomotor movement (Pierce and Besharse 1985;Burnside 2001), outer segment disc shedding and membrane renewal (LaVail 1980;Besharse and Dunis 1983), morphological changes at synaptic ribbons (Adly et al. 1999), gene expression (Korenbrot and Fernald 1989;Pierce et al. 1993;Haque et al. 2002), and the gating behavior of ion channels (Ko et al. 2001) among other photoreceptor activities. Importantly, photoreceptors are more sensitive to intense light damage at night than during the day, even in animals that have been maintained in constant darkness (DD) for several days after circadian lightdark (LD) cycle entrainment (Vaughan et al. 2002).Photoreceptors are non-spiking neurons, and they release glutamate continuously in the darkness as a result of depolarization-evoked activation of L-type voltage-gated calcium channels (VGCCs) (Barnes and Kelly 2002). The synthesis and release of the neurohormone melatonin in photoreceptors is also under circadian control (Cahill and Besharse 1993;Bernard et al. 1997;Ivanova and Iuvone 2003b), and melatonin synthesis and release can be blocked by dihydropyridine inhibitors of L-type VGCCs (Iuvone and Besharse 1986;Ivanova and Iuvone 2003a). In this regard, we previously showed that there is a circadian regulation of the apparent affinity of cGMP-gated ion channels (CNGCs) for cG...

BackgroundMicroRNA-223 (miR-223) has been shown to be a potential diagnostic and prognostic marker for several cancers. In addition, miR-223 has been reported to suppress osteosarcoma cell proliferation in vitro. However, the clinical value of miR-223 is still unknown.MethodsWe detected the expression of miR-223 expression in the serum of osteosarcoma patients and in osteosarcoma cancer cells using RT-PCR. We compared the serum expression of miR-223 with the clinicopathological characteristics and survival of osteosarcoma patients. Finally, we explored the role of miR-223 on the invasion of osteosarcoma cancer cells using cell migration and invasion assays.ResultsWe observed that the expression of miR-223 was significantly decreased in the serum of osteosarcoma patients and osteosarcoma cancer cells compared to healthy controls (P<0.01). Moreover, a receiver operating characteristic (ROC) curve analysis indicated that serum miR-223 is a potential diagnostic marker of osteosarcoma with an area under the ROC curve (AUC) of 0.956. Importantly, the patients with a lower expression of miR-223 tended to have distant metastasis (P<0.001) and a more advanced clinical stage (P<0.001). In addition, the survival time of patients with low miR-223 expression was significantly shorter compared to patients with high miR-223 expression (P<0.001). Furthermore, we found that miR-223 could inhibit the migration and invasion of osteosarcoma cells.ConclusionsmiR-223 might be related to the metastasis of osteosarcoma and could be used as a potential diagnostic and prognostic biomarker in osteosarcoma.

OBJECTIVEBoth structural allograft and PEEK have been used for anterior cervical discectomy and fusion (ACDF). There are reports that PEEK has a higher pseudarthrosis rate than structural allograft. The authors compared pseudarthrosis, revision, subsidence, and loss of lordosis rates in patients with PEEK and structural allograft.METHODSThe authors performed a retrospective review of patients who were treated with ACDF at their hospital between 2005 and 2017. Inclusion criteria were adult patients with either PEEK or structural allograft, anterior plate fixation, and a minimum 2-year follow-up. Exclusion criteria were hybrid PEEK and allograft cases, additional posterior surgery, adjacent corpectomies, infection, tumor, stand-alone or integrated screw and cage devices, bone morphogenetic protein use, or lack of a minimum 2-year follow-up. Demographic variables, number of treated levels, interbody type (PEEK cage vs structural allograft), graft packing material, pseudarthrosis rates, revision surgery rates, subsidence, and cervical lordosis changes were collected. These data were analyzed by Pearson’s chi-square test (or Fisher’s exact test, according to the sample size and expected value) and Student t-test.RESULTSA total of 168 patients (264 levels total, mean follow-up time 39.5 ± 24.0 months) were analyzed. Sixty-one patients had PEEK, and 107 patients had structural allograft. Pseudarthrosis rates for 1-level fusions were 5.4% (PEEK) and 3.4% (allograft) (p > 0.05); 2-level fusions were 7.1% (PEEK) and 8.1% (allograft) (p > 0.05); and ≥ 3-level fusions were 10% (PEEK) and 11.1% (allograft) (p > 0.05). There was no statistical difference in the subsidence magnitude between PEEK and allograft in 1-, 2-, and ≥ 3-level ACDF (p > 0.05). Postoperative lordosis loss was not different between cohorts for 1- and 2-level surgeries.CONCLUSIONSIn 1- and 2-level ACDF with plating involving the same number of fusion levels, there was no statistically significant difference in the pseudarthrosis rate, revision surgery rate, subsidence, and lordosis loss between PEEK cages and structural allograft.

Aberrant nucleus pulposus cell proliferation is implicated in the development of intervertebral disk degeneration (IDD). Recent studies have suggested that long noncoding RNAs (lncRNAs) can modulate cell proliferation in several pathological conditions. Here, we indicate that expression of SNHG1 was upregulated in IDD tissues compared with control tissues and that higher SNHG1 expression was associated with disk degeneration grade. In addition, we show that ectopic expression of SNHG1 promoted nucleus pulposus (NP) cell proliferation and increased the PCNA and cyclin D1 expression in NP cells. Ectopic expression of SNHG1 inhibited miR-326 expression in nucleus pulposus cells and promoted CCND1 expression, which is a direct target gene of SNHG1. Moreover, we demonstrate that expression of miR-326 was downregulated in IDD tissues compared with control tissues and that lower SNHG1 expression was associated with disk degeneration grade. Expression of miR-326 was negatively associated with SNHG1 expression in disk degeneration tissues. Overexpression of miR-326 inhibited NP cell growth and inhibited PCNA and cyclin D1 expression in NP cells. Furthermore, we show that overexpression of SNHG1 promoted nucleus pulposus cell proliferation through inhibiting miR-326 expression. These data shed novel light on the role of SNHG1 in the pathogenesis of IDD.

Growing evidences suggested that microRNAs (miRNAs) played important roles in the development of intervertebral disc degeneration (IDD). However, the expression level and function of miR-665 in IDD remain unknown. In this study, we showed that the expression level of miR-665 was upregulated in degenerative human NP samples. In addition, miR-665 expression level gradually increased with the exacerbation of disc degeneration grade. Moreover, miR-665 expression level was positively associated with the Pfirrmann grade. Ectopic expression of miR-665 promoted NP cell growth. Furthermore, miR-665 overexpression decreased aggrecan and Col II expression and ectopic expression of miR-665 increased MMP-3 and MMP-13 expression in NP cell. We identified growth differentiation factor 5 (GDF5) was a direct target gene of miR-665 in NP cell and enforced expression of miR-665 decreased GDF5 expression. Elevated expression of miR-665 enhanced NP cell proliferation and decreased aggrecan and Col II expression. In addition, ectopic expression of miR-665 increased MMP-3 and MMP-13 expression through inhibiting GDF5 expression in NP cells. These results suggested that dysregulated miR-665 expression might act an important role in the development of IDD.

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Increasing evidence suggests that capsaicin may play a role in modulating neuronal function and controlling motor behavior. However, the underlying mechanism is still unclear and the activation of transient receptor potential vanilloid 1 (TRPV1) might be involved in. This study investigated the potential neuroprotective role of capsaicin in a rat model of 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Capsaicin was treated intraperitoneally for the 6-OHDA induced PD rats and the locomotor activity and abnormal involuntary movements were found alleviated. Besides, brain oxidative stress (lipid peroxidation, superoxide dismutase and catalase) was also assessed, and oxidative insults were investigated relieved. Both the expression of tyrosine hydroxylase and TRPV1 were increased in the striatal and substantia nigra areas of 6-OHDA induced rats after the treatment of capsaicin by the semi-quantitative analysis of Western Blot. And the immunostaining of substantia nigra further suggested that capsaicin might protect against dopaminergic neuronal loss. Our results showed that TRPV1 might be a novel therapeutic target for PD.

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