Background
Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ
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, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals.
Methods
One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ
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, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time.
Results
Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ
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, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD.
Conclusions
Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.
Electronic supplementary material
The online version of this article (10.1186/s13024-019-0309-5) contains supplementary material, which is available to authorized users.
Abstract. Pancreatic cancer remains a challenging disease worldwide. Cryptotanshinone (CPT) is one of the active constituents of Salvia miltiorrhiza Bunge and exhibits significant antitumor activities in several human cancer cells. However, the efficacy and molecular mechanism of CPT in pancreatic cancer remains to be elucidated. In the present study, the effect of CPT on the proliferation, apoptosis and cell cycle of human pancreatic cancer cell BxPC-3 cells was evaluated. The results demonstrated that CPT inhibited proliferation of the BxPC-3 cells in a concentration-dependent manner, and significantly induced cell apoptosis and cell cycle arrest. The protein levels of cleaved caspase-3, caspase-9 and poly ADP ribose polymerase were upregulated, while the levels of c-myc, survivin and cyclin D1 were downregulated following treatment with CPT. In addition, CPT decreased the activities of signal transducer and activator of transcription 3 (STAT3) and several upstream regulatory signaling pathways after 24 h. However, CPT only inhibited the phosphorylation of STAT3 Tyr705 within 30 min, without marked effects on the phosphorylation of the other proteins. These results suggested that the inhibition of STAT3 activity by CPT was directly and independent of the upstream regulators in human pancreatic cancer. The present study demonstrated that CPT exerts anticancer effects by inducing apoptosis and cell cycle arrest via inhibition of the STAT3 signaling pathway in human BxPC-3 cells.
Transcatheter arterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) because of its survival benefit, although its clinical effect is still far from satisfactory. In China, there has been a long history of using traditional Chinese medicine in the treatment of liver cancer and other malignancies. In this study, the authors evaluated the effect of combined therapy with TACE and JDF granule preparation (a traditional Chinese herbal medicine formula) in the treatment of patients with unresectable HCC on survival. Clinical data, including baseline, performance status change, and survival time of 165 patients with unresectable HCC seen between January 2002 and December 2007 were retrospectively analyzed. Among the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and 85 patients (control group) received TACE alone. The survival rate of both groups was calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model. The median overall survival was 9.2 months (95% confidence interval [95% CI], 6.94-1.46) in the study group versus 5.87 months (95% CI, 4.21-7.52) in the control group.In the study group (TACE þ JDF), 1-year, 2-year, and 3-year survival rates were 41.2%, 18.4%, and 9.6%, respectively. The Cox regression analysis revealed the therapy model to be an independent predictor of patient prognosis. Current study data demonstrated that TACE combined with JDF granule preparation could improve the prognosis of patients. TACE combined with JDF granule preparation may prolong survival of patients with unresectable HCC.
Cryptotanshinone (CPT), a diterpene quinone isolated from Salvia miltiorrhiza, is recently reported to have obvious anticancer activities against diverse cancer cells. However, the effect and regulatory mechanism of CPT remain unclear in human chronic myeloid leukemia (CML) cells. In this study, we investigated the antiproliferative activity of CPT on the multidrug resistant CML cells K562/ADM. Our results demonstrated that CPT decreased the cell viability of K562/ADM cells by inducing cell cycle arrest and apoptosis through suppressing the expression of cyclin D1 and Bcl-2. Further studies indicated that CPT mainly functions at post-transcriptional levels, suggesting the involvement of eukaryotic initiation factor 4E (eIF4E). CPT significantly reduced the expression and activity of eIF4E in K562/ADM cells. Overexpression of eIF4E obvious conferred resistance to the CPT antiproliferation and proapoptotic activity as well as the cyclin D1 and Bcl-2 expressions. Knockdown of eIF4E significantly reduced the inhibitory effect of CPT in K562/ADM, confirming the participation of eIF4E during CPT function process. More importantly, the relative inhibitory efficiency of CPT positively correlated with the reductions on eIF4E in primary CML specimens. These results demonstrated that CPT played antitumor roles in K562/ADM cells by inhibiting the eIF4E regulatory system. Our results provide a novel anticancer mechanism of CPT in human CML cells.
In conclusion, although single use of Dex or GS may improve some indices of adverse effects after TACE, the combination of Dex and GS can systematically prevent and treat the postembolization syndrome following TACE.
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