Predictors of poor outcomes in First-Event Ischemic Stroke as assessed by Magnetic Resonance Imaging

Purpose: Stroke is the third most common cause of mortality worldwide and is a major cause of permanent disability. The purposed of the study was to better understand the risk factors for poor outcomes following ischemic stroke requiring treatment. Methods: Three hundred seventy patients with first-event ischemic stroke were enrolled. Good outcomes was defined as a using the Modified Rankin Scale (MRS) score ≤3 without any cardiovascular event, while poor outcomes were any of the following end points: MRS >3 at 3 months, recurrent stroke or death. Prognostic variables for poor outcomes were analyzed based on a stepwise logistic regression model. Results: Seventy-eight patients had poor outcomes (21%, 78/370), assessed at a minimum of six-month follow-up. Higher mean National Institutes of Health Stroke Scale (NIHSS) scores at presentation, presence of early neurologic deterioration (END) and higher mean high-sensitivity C-reactive protein (hs-CRP) levels were associated with poor outcomes at discharge. Furthermore, both NIHSS at presentation and the presence of END were associated with poor outcomes, assessed at a minimum of six-month follow-up. Conclusion: A higher mean initial NIHSS score implies not only severe neurologic deficits but also an increased risk of poor outcomes. Since END following ischemic stroke is frequently associated with poor outcomes, more attention should be directed to providing adequate treatment to patients in the acute stage, especially for high risk patients

Crude Extracts of Agaricus brasiliensis Induce Apoptosis in Human Oral Cancer CAL 27 Cells through a Mitochondria-dependent Pathway

In Taiwan, oral cancer is the fourth leading cause of male cancer mortality, and is still increasing. The Basiodiomycete, Agaricus brasiliensis Mural (ABM) is a dietary mushroom and has been known for its immune-enhancing, antitumor, antioxidation, antiviral and anti-mutagenesis functions. However, the exact anticancer mechanisms of ABM on human oral cancer cells are still unclear. In the present study, we investigated the effects of 50% ethanol crude extracts and hot water extracts of ABM on oral cancer CAL 27 cells. We observed that 0.9 mg/ml and 0.7 mg/ml of ABM 50% ethanol crude extracts and hot water, respectively, caused morphological changes and significantly reduced cell viability after 48-h treatment. The results showed that both extracts of ABM inhibited cell proliferation, increased the Ca(2+) release, reduced the mitochondria membrane potential (Delta Psi m), and caused cell cycle arrest in the G(0)/G(1) I phase, which contributed to apoptosis. Additionally, ABM induced DNA fragmentation, a characteristic of apoptosis and the expressions of apoptosis-related proteins, including apoptosis-inducing factor, cytochrome c, and caspase-3, were increased. Overall, we demonstrated that 50% ethanol crude extract and hot water extracts of ABM were able to induce apoptotic cell death in CAL 27 cells via the release of cytochrome c from mitochondria into the cytoplasm and activation of caspase-3 in vitro

Casticin Inhibits A375.S2 Human Melanoma Cell Migration/Invasion through Downregulating NF-κB and Matrix Metalloproteinase-2 and -1

Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti-metastasis effects of casticin on A375.S2 melanoma cells by using a non-lethal concentration. First; we used an adhesion assay to test the A375.S2 cells’ adhesion ability after treatment with casticin. We next investigated the cell migration ability after casticin treatment by using a wound healing assay to prove that the migration of A375.S2 cells can be inhibited by casticin and double checked the results using the transwell-migration assay. The suppressive effects on matrix metalloproteinase-2; and -9 (MMP-2; and -9) activities were examined by gelatin zymography. Furthermore, western blotting was used to investigate the protein level changes in A375.S2 cells. We found that p-EGFR; Ras and p-ERK1/2 are decreased by casticin, indicating that casticin can down-regulate the migration and invasion ability of A375.S2 cells via the p-EGFR/Ras/p-ERK pathway. The NF-κB p65 and p-ERK levels in nuclear proteins are also decreased by treatment with casticin. An EMSA assay also discovered that the NF-κB p65 and DNA interaction is decreased. NF-κB p65 protein level was examined by immunofluorescence staining and also decreased. Our findings suggest that casticin has anti-metastatic potential by decreasing the invasiveness of A375.S2 cells. We also found that casticin suppressed A375.S2 cell proliferation and cell adhesion ability, but did not affect cell death, as examined using cytometry and a collagen adhesion assay. Based on these observations, casticin could be used as an inhibitor of migration and invasion of human melanoma cells in the future

Cucurbitacin E Induces G2/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells

Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (ΔΨm) and annexin V/PI staining were determined by flow cytometry. The protein levels were measured by Western blotting. Our results demonstrated that cucurbitacin E-induced G2/M arrest was associated with a marked increase in the levels of p53, p21 and a decrease in phospho-signal transducer and activator of transcription 3 (STAT3), cyclin-dependent kinase 1 (CDK1) and cyclin B. Cucurbitacin E-triggered apoptosis was accompanied with up-regulation of Fas/CD95, truncated BID (t-BID) and a loss of ΔΨm, resulting in the releases of cytochrome c, apoptotic protease activating factor 1 (Apaf-1) and apoptosis-inducing factor (AIF), and sequential activation of caspase-8, caspase-9, and caspase-3. Our findings provided the first evidence that STAT3/p53/p21 signaling, Fas/CD95 and mitochondria-dependent pathways play critical roles in cucurbitacin E-induced G2/M phase arrest and apoptosis of T24 cells

Additional file 3 of The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study

Additional file 3: Figure S2. Subgroup analysis of forest plot of HR for SGLT2i versus glucagon-like peptide-1 receptor agonist (GLP-1RA) among patients with T2D after PSM. Subgroup analysis revealed that use of SGLT2i was associated with a lower risk of new-onset AF compared with use of DPP4i across most subgroups. Use of SGLT2i was associated with greater reductions in new-onset AF events in subgroup including those without concomitant use of sulfonylurea when compared with GLP-1RA (P interaction < 0.01)

Additional file 3 of The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study

Additional file 3: Figure S2. Subgroup analysis of forest plot of HR for SGLT2i versus glucagon-like peptide-1 receptor agonist (GLP-1RA) among patients with T2D after PSM. Subgroup analysis revealed that use of SGLT2i was associated with a lower risk of new-onset AF compared with use of DPP4i across most subgroups. Use of SGLT2i was associated with greater reductions in new-onset AF events in subgroup including those without concomitant use of sulfonylurea when compared with GLP-1RA (P interaction < 0.01)

Additional file 2 of The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study

Additional file 2: Figure S1. Subgroup analysis of forest plot of hazard ratio (HR) for sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) among patients with type 2 diabetes (T2D) after propensity score matching (PSM). Subgroup analysis revealed that use of SGLT2i was associated with a lower risk of new-onset AF compared with use of DPP4i across most subgroups. It is noted that dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02)

Additional file 4 of The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study

Additional file 4: Figure S3. Subgroup analysis of forest plot of HR for GLP-1RA versus DPP4i among patients with T2D after PSM. There was no difference of the risk of incident AF between the GLP-1RA and DPP4i across all subgroups (P interaction > 0.05)