angiogenin and Stroke

Stroke is a devastating event with a limited choice of intervention. Benzoinum is frequently used to treat stroke in traditional Chinese medicine. Our team has found that the neuroprotection of benzoinum may related to angiogenesis, but the exact biological mechanism is unclear. The objective of this study was to explore its biological mechanism of angiogenesis in cerebral ischemia model rats.. First, network pharmacology and molecular docking were performed to predict the possible targets and mechanisms of benzoinum in treating ischemic stroke. The best dose was then selected according to pharmacodynamic indexes such as those for neurological deficit, cerebral infarction rate, and brain histopathology in middle cerebral artery occlusion (MCAO) model rats. Finally, RT-PCR, Western Blot and immunohistochemical analysis were applied to verify the prediction results from molecular docking.. Network pharmacology and molecular docking demonstrated that the targets of treating cerebral ischemia were PDE4D, ACE and TTR, and the mechanism may be related to the ACE-AngI-VEGF signaling pathway. Experimental verification results suggested that 0.50 g/kg and 1.00 g/kg benzoinum could significantly protect against neurological deficit and reduce cerebral infarction rate in the cerebral cortex and hippocampus in MCAO model rats. At an optimal dose, benzoinum could significantly up-regulate VEGF, SHH and ANG-1, yet down-regulate ACE expression in MCAO model rats.. Balsamic acid is the active ingredient of benzoinum that protects against ischemic stroke and the possible mechanism is related to the promotion of angiogenesis via regulating ACE-AngI-VEGF pathway.

Topics: Animals; Brain Ischemia; Cerebral Cortex; Disease Models, Animal; Drugs, Chinese Herbal; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Male; Molecular Docking Simulation; Neovascularization, Pathologic; Neuroprotective Agents; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ribonuclease, Pancreatic; Small Molecule Libraries; Stroke; Vascular Endothelial Growth Factor A

The disruption of appropriate cellular stress responses is implicated in the pathogenesis of different neurological disorders including ischemic injury. Early diagnosis and treatment are often associated with better prognosis in ischemic stroke patients. Thus, there is an urgent need to improve the speed and accuracy of stroke diagnosis by developing highly sensitive stroke biomarkers. We recently reported that transfer RNA (tRNA) was involved in cell stress response pathways. Under cell stress conditions, mature tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived stress-induced RNA (tiRNA). To study tiRNA generation in an in vitro model of ischemic-reperfusion injury, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which detects 1-methyladenosine (m

Topics: Adenosine; Animals; Biomarkers; Cell Survival; Glucose; Hypoxia; Ischemia; Neurons; Oxygen; PC12 Cells; Rats; Reperfusion Injury; Ribonuclease, Pancreatic; RNA, Transfer; Stress, Physiological; Stroke

Our previous studies have found that bone-marrow-stromal cells (BMSC) therapy improves functional recovery after stroke in non-diabetic rats while increases brain hemorrhage and induces arteriosclerosis-like changes in type-one-diabetic (T1DM) rats. Niaspan treatment of stroke increases vascular stabilization, decreases brain hemorrhage and blood-brain-barrier (BBB) leakage in T1DM rats. We therefore tested the hypothesis that combination therapy of BMSC with Niaspan attenuates the side effects of BMSC monotherapy in T1DM rats.. T1DM-rats induced by streptozotocin were subjected to 2 hours of middle-cerebral-artery occlusion (MCAo) and treated with: 1) PBS; 2) BMSC (5×10(6)); 3) Niaspan (40 mg/kg) daily for 14 days; 4) BMSC (5×10(6)) +Niaspan (40 mg/kg, daily for 14 days) combination starting at 24 hours after MCAo. All rats were monitored for 14 days.. Combination BMSC+Niaspan treatment of T1DM-MCAo rats did not increase brain hemorrhage, and significantly decreased BBB leakage and vascular arteriosclerosis-like changes as well as decreased Angiogenin, matrix metalloproteinase 9 (MMP9) and ED1 expression in ischemic brain and internal-carotid-artery compared to non-treatment control and BMSC monotherapy animals.. Combination therapy using BMSC with Niaspan decreases BBB leakage and cerebral arteriosclerosis-like changes. These beneficial effects may be attributed to the decreased expression of Angiogenin, MMP9 and ED1.

Topics: Animals; Blood-Brain Barrier; Diabetes Mellitus, Type 1; Disease Models, Animal; Ectodysplasins; Intracranial Arteriosclerosis; Male; Matrix Metalloproteinase 9; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Niacin; Permeability; Protein Binding; Protein Transport; Rats; Ribonuclease, Pancreatic; Stroke; Stroke Rehabilitation

Adipokines such as adiponectin and resistin, as well as angiogenin, may be associated with inflammation and atherosclerosis. The relationship between their levels and prognosis in high risk patients is, however, still unclear. The aim of this study was to evaluate the prognostic value of these adipokines in patients with stable multivessel coronary artery disease (MCAD).. The study group comprised 107 MCAD patients (74% males, mean age 63 ± 8 years). Adiponectin, resistin and angiogenin plasma levels were measured at admission and after 1-year follow-up. Primary end point (major adverse cardiac and cerebrovascular events--MACCE) was defined as cardiac death, nonfatal myocardial infarction, stroke, and hospitalization for angina or heart failure over a 1-year period.. After 1-year follow-up, 9 (8%) patients died, all from cardiovascular causes. Primary end point was experienced by 32% of patients. Surgical treatment (CABG) was received by 51% of patients, while 49% were treated medically alone. Total cholesterol concentration levels ≥ 173 mg/dl were associated with a 7-fold increase (OR 7.3; 95% CI, 1.6-33.0); LDL ≥ 93.5 mg/dl with a 16-fold increase (OR 16.3; 95% CI, 2.8-93.8), and resistin ≥ 17.265 ng/ml with a 13-fold increase in MACCE risk (OR 13.5; 95% CI, 2.3-80.3). In multivariate analysis, a medical treatment strategy (p = 0.001), a higher CCS class (p = 0.004), resistin levels (p = 0.003) and a higher Gensini score (p = 0.03) were independent predictors of MACCE.. In stable patients with MCAD, elevated plasma resistin (as opposed to adiponectin or angiogenin) is a strong, independent predictive factor for the occurrence of MACCE over 1-year follow-up.

Topics: Adiponectin; Aged; Coronary Angiography; Coronary Artery Disease; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Heart Arrest; Humans; Male; Middle Aged; Poland; Prognosis; Resistin; Ribonuclease, Pancreatic; Statistics, Nonparametric; Stroke