Estrogen receptor ß upregulated by lncRNA-H19 to promote cancer stem-like properties in papillary thyroid carcinoma.

Estrogen receptor ß (ERß) plays critical roles in thyroid cancer progression. However, its role in thyroid cancer stem cell maintenance remains elusive. Here, we report that ERß is overexpressed in papillary thyroid cancer stem cells (PTCSCs), whereas ablation of ERß decreases stemness-related factors expression, diminishes ALDH+ cell populations, and suppresses sphere formation ability and tumor growth. Screening estrogen-responsive lncRNAs in PTC spheroid cells, we find that lncRNA-H19 is highly expressed in PTCSCs and PTC tissue specimens, which is correlated with poor overall survival. Mechanistically, estradiol (E2) significantly promotes H19 transcription via ERß and elevates H19 expression. Silencing of H19 inhibits E2-induced sphere formation ability. Furthermore, H19 acting as a competitive endogenous RNA sequesters miRNA-3126-5p to reciprocally release ERß expression. ERß depletion reverses H19-induced stem-like properties upon E2 treatment. Appropriately, ERß is upregulated in PTC tissue specimens. Notably, aspirin attenuates E2-induced cancer stem-like traits through decreasing both H19 and ERß expression. Collectively, our findings reveal that ERß-H19 positive feedback loop has a compelling role in PTCSC maintenance under E2 treatment and provides a potential therapeutic targeting strategy for PTC.

Efficacy of telemedicine for thrombolytic therapy in acute ischemic stroke: a meta-analysis.

The aim of this study was to assess the benefits of telemedicine in the delivery of thrombolytic therapy for patients with acute ischemic stroke. We performed a meta-analysis using combinations of the following terms: telestroke, telemedicine, tissue plasminogen activator/t-PA, and acute ischemic stroke. The primary outcome was favorable outcome based on the modified Rankin score. Secondary outcomes were incidence of symptomatic intracranial hemorrhage and overall mortality. We found no significant difference in favorable outcome between the telemedicine and control groups, and no significant difference was found between these groups in the rate of symptomatic intracranial hemorrhage or overall mortality. Patients with acute ischemic stroke who were treated with intravenous thrombolysis had similar outcomes regardless of whether telemedicine was used or they were treated in-person at a medical facility. Telemedicine can be used to support hospitals with limited experience in administering thrombolytic therapy for stroke.

Effectiveness of Telemedicine for Controlling Asthma Symptoms: A Systematic Review and Meta-analysis.

BACKGROUND: The effectiveness of telemedicine for the management of chronic diseases is unclear. This study examined the effectiveness of telemedicine in relieving asthma symptoms. MATERIALS AND METHODS: A systematic review of the Medline, Cochrane, EMBASE, and Google Scholar databases was conducted until December 31, 2013 using the following key words: "asthma," "telemedicine," "telehealth," "e-health," "mobile health," "Internet," "telecommunication," "telemanagement," "remote," and "short message service." Inclusion criteria were randomized controlled trial, a diagnosis of asthma, the majority of the patients were ≥18 years of age, and intervention involved any format of telemedicine. A meta-analysis of eligible studies was conducted with the primary outcome being change of asthma symptoms. RESULTS: Of 813 articles identified, 11 were included in the qualitative synthesis, and 6 were included in the meta-analysis. Among the 11 studies, there were 1,460 patients in the intervention groups and 1,349 in the control groups, and the total numbers of participants ranged from 12 to 481 in the intervention groups and from 12 to 487 in the control groups. The mean age of patients ranged in the intervention groups from 34.4 to 54.6 years and in the control groups from 30.7 to 56.4 years. The treatment duration ranged from 0.5 to 12 months. The meta-analysis of six eligible studies revealed no significant difference in asthma symptom score change between the telemedicine and control groups (pooled Hedges's g=0.34, 95% confidence interval=-0.05 to 0.74, Z=1.69, p=0.090). CONCLUSIONS: Telemedicine interventions do not appear to improve asthma function scores, but other benefits may be present.

Clinical- and cost-effectiveness of telemedicine in type 2 diabetes mellitus: a systematic review and meta-analysis.

Emerging telemedicine programs offer potential low-cost solutions to the management of chronic disease. We sought to evaluate the clinical effectiveness and cost effectiveness of telemedicine approaches on glycemic control in patients with type 2 diabetes mellitus. Using terms related to type 2 diabetes and telemedicine, MEDLINE, Cochrane, EMBASE, and CINAHL Plus were searched to identify relevant studies published through February 28, 2014. Data from identified clinical trials were pooled according to telemedicine approach, and evaluated using conventional meta-analytical methods. We identified 47 articles, from 35 randomized controlled trials, reporting quantitative outcomes for hemoglobin A1c (HbA1c). Twelve of the 35 studies provided intervention via telephone, either in the form of a call or a text message; 19 studies tested internet-based programs, employing video-conferencing and/or informational websites; and four studies used interventions involving electronically transmitted recommendations made by clinicians in response to internet-based reporting by patients. Overall, pooled results from these studies revealed a small, but statistically significant, decrease in HbA1c following intervention, compared to conventional treatment (pooled difference in means=-0.37, 95% CI=-0.49 to -0.25, Z=-6.08, P<0.001). Only two of the 35 studies included assessment of cost-effectiveness. These studies were disparate, both in terms of overall expense and relative cost-effectiveness. Optimization of telemedicine approaches could potentially allow for more effective self-management of disease in type 2 diabetes patients, though evidence to-date is unconvincing. Furthermore, significant publication bias was detected, suggesting that the literature should be interpreted cautiously.

Trace amounts of copper exacerbate beta amyloid-induced neurotoxicity in the cholesterol-fed mice through TNF-mediated inflammatory pathway.

Evidence has been gathered to suggest that trace amounts of copper induce neurotoxicity by interaction with elevated cholesterol in diet. Step-through task and Morris water maze task were used to evaluate cognitive function in the animals. Although a 16-week copper treatment alone in mice showed no significant change in learning and memory performances, cholesterol treatment significantly induced learning and memory impairments, which could be exacerbated by the co-treatment with copper. Immunohistochemical studies revealed that trace amounts of copper further stimulated the amyloid precursor protein (APP) upregulation and contributed to amyloid beta-peptide (Abeta) deposition in the brain of cholesterol-fed mice. Western blot analysis showed that copper also increased the protein expression levels of tumor necrosis factor-alpha (TNF-alpha) and the degradation of IkappaB proteins in the brain of cholesterol-fed mice. Furthermore, increased production of high inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expressions were detected in the hippocampus and cerebral cortex of copper and cholesterol co-treated mice by immunohistochemical analysis. These findings suggest that trace amounts of copper could induce APP upregulation, activate inflammatory pathway and exacerbate neurotoxicity in cholesterol-fed mice.

Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose.

Ursolic acid (UA), a pentracyclic triterpene, is reported to have an antioxidant activity. Here we assessed the protective effect of UA against the d-galactose (D-gal)-induced neurotoxicity. We found that UA markedly reversed the D-gal induced learning and memory impairment by behavioral tests. The following antioxidant defense enzymes were measured: superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). The content of the lipid peroxidation product malondialdehyde (MDA) was also analyzed. Our results indicated that the neuroprotective effect of UA against D-gal induced neurotoxicity might be caused, at least in part, by the increase in the activity of antioxidant enzymes with a reduction in lipid peroxidation. And UA also inhibited the activation of caspase-3 induced by D-gal. Furthermore, we found that UA significantly increased the level of growth-associated protein GAP43 in the brain of D-gal-treated mice. These results suggest that the pharmacological action of UA may offer a novel therapeutic strategy for the treatment of age-related conditions.

Trace amounts of copper induce neurotoxicity in the cholesterol-fed mice through apoptosis.

Evidence has been gathered to suggest that trace amounts of copper induce neurotoxicity by interaction with elevated cholesterol in diet. Copper treatment alone showed no significant learning and memory impairments in behavioral tasks. However, copper-induced neurotoxicity was significantly increased in mice given elevated-cholesterol diet. Trace amounts of copper decreased the activity of SOD and increased the level of malondialdehyde (MDA) in the brain of cholesterol-fed mouse. Copper also caused an increase in amyloid precursor protein (APP) mRNA level and the activation of caspase-3 in the brain of cholesterol-fed mice. The apoptosis-induced nuclear DNA fragmentation was detected in the brain of those mice by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling staining. These findings suggest that trace amounts of copper induce neurotoxicity in cholesterol-fed mice through apoptosis caused by oxidative stress.

Quercetin reverses D-galactose induced neurotoxicity in mouse brain.

We assessed the neuroprotective effects of quercetin-feeding at doses of 5 and 10 mg/(kg day) on Kunming mice injected daily with D-gal (50 mg/(kg day)) by behavioral tests. Quercetin-fed mice showed higher activity upon induction by new environmental stimuli, lower anxiety and higher novelty-seeking behavior in the open field tasks, and significantly improved learning and memory ability in step-through and Morris water Maze tests compared with D-gal-treated mice. We further investigated the mechanisms involved in the neuroprotective effects of quercetin on mouse brain. Quercetin significantly increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) level. These results imply that quercetin can reverse oxidant impairment induced by D-gal in mouse brain. Neurotoxicity is also associated with Ca(2+) overload induced by oxidant stress. Quercetin could maintain the Ca(2+) homeostasis in the brain of D-gal-treated mice. Furthermore, we also examined the expression of growth-associated protein GAP43 mRNA in mouse brain by in situ hybridization. We found that quercetin dramatically elevated the GAP43 mRNA expression in the brain of D-gal-treated mice to regenerate normal function of neurons against the cellular injury caused by D-gal.