Aqueous Extract of Origanum majorana at Low Temperature (0°C) Promotes Mitochondrial Fusion and Contributes to Induced Apoptosis in Human Breast Cancer Cells.

Marjoram plants have varied pharmacological properties because they contain antioxidants. In the present study, to evaluate the effect of Origanum majorana, gathered from Abha, Saudi Arabia, on the growth of human breast cancer cells using MCF7. Fresh aerial parts from Origanum majorana were extracted at a low temperature (0 ℃/6 hours). Human MCF7 breast cancer cells were then treated with 4 separate fluctuated concentrations of 0, 50, 150, 200 and 350 µg/mL for 24 and 48 hours. The findings showed that Origanum majorana aqueous extract contained absolute phenolic content (TPC) was 58.24 mg equivalent/g DW, and the complete flavonoid content (TFC) 35.31 mg GAE equivalent/g DW in the Origanum majorana aqueous extract. The endurance of MCF7 cells after incubation with aqueous extract diminished, indicating that Origanum majorana is tumour cell selective. Origanum majorana extract increased the mRNA Expression of Apoptotic Genes in MCF7. Majorana aqueous extract expanded the activity of Caspase-7 action specifically at higher concentrations, 150, 200, and 350 µg/ml. Our findings indicate that Origanum majorana could induce apoptosis of human breast cancer cells. This is the first study that provides a basis for the use of aqueous Origanum majorana extracted at low temperature (0 °C/6 hours) as more effective anticancer treatment.

May endovascular thrombectomy without CT perfusion improve clinical outcome?

BACKGROUND: DAWN and DEFUSE-3 trials demonstrated the benefit of endovascular thrombectomy in late-presenting acute ischemic strokes due to anterior circulation large vessel occlusion. The aim of our study is to evaluate results of endovascular thrombectomy in large intracranial vessel occlusion without perfusion CT patient selection. METHODS: we reviewed our prospectively collected endovascular databases for patients with an acute stroke from March 2016 to October 2018, treated after 6 h from stroke onset, without perfusion CT selection. Baseline characteristics, procedural data, and outcomes were evaluated. A good outcome was defined as a 90-day modified Rankin Scale score of 0-2. The association between clinical and procedural parameters and functional outcome was assessed. RESULTS: out of 212 patients 55 were treated after 6 h from stroke onset, 49 of which for an anterior circulation occlusion. 18/49 were functional independent at 90 days (mRS 0-2), Successful recanalization (mTICI 2b to 3) was achieved in 38/49 patients (77 %). Multivariate logistic regression indicated that a low baseline NIHSS was associated with favorable outcome (OR 0.66, 95 % CI 0.52-0.83, p-value 0.001). CONCLUSIONS: in our retrospective analysis, baseline NIHSS is the only parameter that can predict good outcome (90-days mRS 0-2). We confirm data from recent papers assessing that perfusion CT can provide a better patients' selection compared to mCTA for large vessels occlusion treated beyond six hours from symptom onset.

Endovascular treatment for ischemic stroke beyond the time window: A meta-analysis.

Currently, endovascular treatment has been proven to be effective when conducted within 6 hours of symptom onset. However, when patients have symptoms for more than 6 hours, have a daytime-unwitnessed stroke (DUS) or wake up with a stroke (wake-up stroke, WUS), the safety and efficacy of endovascular treatment need to be further elucidated. Therefore, we performed a systematic review and meta-analysis to compare the clinical outcomes of endovascular treatment in patients with ischemic stroke beyond the time window with that ≤6 hours. PubMed, EMBASE, and Ovid MEDLINE were searched from inception to November 2018. The following outcomes were evaluated by a random-effects model: efficacy outcomes, that is, functional independence and successful recanalization, and safety outcomes, that is, symptomatic intracranial hemorrhage and mortality. Subgroup analyses were also performed to examine whether patient or study characteristics were associated with the outcomes. Nine observational studies, including 5192 patients (1414 patients with extended time windows [ETWs]; 3778 patients ≤6 hours), were eligible for analysis. The overall analysis demonstrated that the functional independence was worse in patients with ETWs vs those ≤6 hours (OR, 0.78; 95% CI, 0.68-0.90, P = .0006). However, subgroup analysis showed that there was no significant difference in functional independence between the two groups when patients were selected for a perfusion mismatch by imaging (OR, 1.00; 95% CI, 0.70-1.43, P = 1.000). Therefore, compared with a window ≤6 hours, endovascular treatment with ETWs for ischemic stroke may not result in poor outcomes when patients are typically selected by perfusion techniques.

Mechanical Thrombectomy in Strokes with Large-Vessel Occlusion Beyond 6 Hours: A Pooled Analysis of Randomized Trials.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with or without intravenous thrombolysis is indicated in the acute treatment of ischemic strokes caused by an emergent large-vessel occlusion (ELVO) within 6 hours from symptom onset. However, a significant proportion of patients are referred to comprehensive stroke centers beyond this therapeutic time window. This study performed a pooled analysis of data from trials in which mechanical thrombectomy was performed beyond 6 hours from symptom onset. METHODS: We searched for randomized controlled trials that compared mechanical thrombectomy with the best medical treatment beyond 6 hours for ischemic strokes due to ELVO and reported on between 1990 and April 2018. The intervention group comprised patients treated with mechanical thrombectomy. Statistical analysis was conducted while pooling data and analyzing fixed- or random-effects models as appropriate. RESULTS: Four trials involving 518 stroke patients met the eligibility criteria. There were 267 strokes treated with mechanical thrombectomy, with a median time of 10.8 hours between when the patient was last known to be well to randomization. We observed a significant difference between groups concerning the rate of functional independence at 90 days from stroke, with an absolute difference of 27.5% (odds ratio=3.33, 95% CI=1.81-6.12, p<0.001) and good recanalization (odds ratio=13.17, 95% CI=4.17-41.60, p<0.001) favoring the intervention group. CONCLUSIONS: This meta-analysis confirms the efficacy of mechanical thrombectomy in selected ischemic stroke patients beyond 6 hours from symptom onset. The selection is mainly based on the limited core infarct detected by emergent assessment using neuroimaging techniques.

Mechanical Thrombectomy in Strokes with Large-Vessel Occlusion Beyond 6 Hours: A Pooled Analysis of Randomized Trials

BACKGROUND AND PURPOSE: Mechanical thrombectomy with or without intravenous thrombolysis is indicated in the acute treatment of ischemic strokes caused by an emergent large-vessel occlusion (ELVO) within 6 hours from symptom onset. However, a significant proportion of patients are referred to comprehensive stroke centers beyond this therapeutic time window. This study performed a pooled analysis of data from trials in which mechanical thrombectomy was performed beyond 6 hours from symptom onset. METHODS: We searched for randomized controlled trials that compared mechanical thrombectomy with the best medical treatment beyond 6 hours for ischemic strokes due to ELVO and reported on between 1990 and April 2018. The intervention group comprised patients treated with mechanical thrombectomy. Statistical analysis was conducted while pooling data and analyzing fixed- or random-effects models as appropriate. RESULTS: Four trials involving 518 stroke patients met the eligibility criteria. There were 267 strokes treated with mechanical thrombectomy, with a median time of 10.8 hours between when the patient was last known to be well to randomization. We observed a significant difference between groups concerning the rate of functional independence at 90 days from stroke, with an absolute difference of 27.5% (odds ratio=3.33, 95% CI=1.81–6.12, p < 0.001) and good recanalization (odds ratio=13.17, 95% CI=4.17–41.60, p < 0.001) favoring the intervention group. CONCLUSIONS: This meta-analysis confirms the efficacy of mechanical thrombectomy in selected ischemic stroke patients beyond 6 hours from symptom onset. The selection is mainly based on the limited core infarct detected by emergent assessment using neuroimaging techniques.

The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus.

BACKGROUND & AIMS: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. METHODS: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m(2)) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 µg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). RESULTS: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects. CONCLUSIONS: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.