Efficacy and safety of intracoronary pro-urokinase combined with low-pressure balloon pre-dilatation during percutaneous coronary intervention in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: The efficacy and safety of low-pressure balloon pre-dilatation before intracoronary pro-urokinase (pro-UK) in preventing no-reflow during percutaneous coronary intervention (PCI) remains unknown. This study aimed to evaluate the clinical outcomes of intracoronary pro-UK combined with low-pressure balloon pre-dilatation in patients with anterior ST-segment-elevation myocardial infarction (STEMI). METHODS: This was a randomized, single-blind, investigator-initiated trial that included 179 patients diagnosed with acute anterior STEMI. All patients were eligible for PCI and were randomized into two groups: intracoronary pro-UK combined with (ICPpD group, n = 90) or without (ICP group, n = 89) low-pressure balloon pre-dilatation. The main efficacy endpoint was complete epicardial and myocardial reperfusion. The safety endpoints were major adverse cardiovascular events (MACEs), which were analyzed at 12 months follow-up. RESULTS: Patients in the ICPpD group presented significantly higher TIMI myocardial perfusion grade 3 (TMPG3) compared to those in the ICP group (77.78% versus 68.54%, P = 0.013), and STR ≥ 70% after PCI 30 min (34.44% versus 26.97%, P = 0.047) or after PCI 90 min (40.0% versus 31.46%, P = 0.044). MACEs occurred in 23 patients (25.56%) in the ICPpD group and in 32 patients (35.96%) in the ICP group. There was no difference in hemorrhagic complications during hospitalization between the groups. CONCLUSION: Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI. TRIAL REGISTRATION: 2019xkj213.

Scutellaria baicalensis Georgi stems and leaves flavonoids promote neuroregeneration and ameliorate memory loss in rats through cAMP-PKA-CREB signaling pathway based on network pharmacology and bioinformatics analysis.

The aim of this study was to investigate the possible molecular mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) in Alzheimer's disease (AD). The active ingredients of SSF and their targets were identified via network pharmacology and bioinformatics analysis. To test the successful establishment of a rat model of AD by Aß25-35 combined with RHTGF-ß1 and AlCl3, the Morris water maze test was used. To intervene, three different doses of SSF were administered. The model group and the control group were included among the parallel groups. A shuttle box test, immunohistochemistry, an enzyme-linked immunosorbent assay, qPCR and Western blot were performed to verify the results. Based on the intersection of genes among AD disease targets, SSF component targets, and differentially expressed genes in the single cell dataset GSE138852 and bulk-seq dataset GSE5281, nine genes related to the action of SSF on AD were identified. SSF have an important anti-AD pathway in the cAMP signaling pathway. SSF can ameliorate the conditioned memory impairment, augment Brdu protein expression and cAMP content; and differentially regulate the mRNA and protein expressions of GPCR, Gαs, AC1, PKA, and VEGF. The cAMP-PKA-CREB pathway in the SSF may mediate the ability of the SSF to ameliorate the composite-induced memory loss and nerve regeneration in rats induced by composite Aß.

Flavonoids From Stems and Leaves of Scutellaria Baicalensis Georgi Improve Composited Aß-Induced Alzheimer's Disease Model Rats' Memory and Neuroplasticity Disorders.

AIM: The study aims to investigate the effects and mechanism of flavonoids from stems and leaves of Scutellaria baicalensis Georgi (SSF) on the disorders in learning and memory and neuroplasticity induced by beta amyloid 25-35 (Aß25-35) combined with aluminum trichloride (AlCl3) and human recombinant transfer factor-ß1 (RHTGF-ß1) (composited Aß) in rats. METHODS: A rat Alzheimer's disease (AD) model was established by intracerebroventricular injection of Aß25-35 combined with AlCl3 and RHTGF-ß1. The successful AD model of rats was screened with a Morris water maze. The successful model rats were randomly divided into a model group and three doses of SSF treated group. The Morris water maze was used to detect the rats' learning and memory abilities. The real-time fluorescence quantitative (qPCR) was applied to assay the mRNA expressions of CaM, CamkIV and Ferritin, as well as the neuroplasticity factors of HuB, HuC and HuD. The Western blotting was used to measure the protein expressions of CaM, CamkIV, HuB/D, HuC+HuD and Ferritin in the CaM-CamkIV-CREB signal pathway. RESULTS: Compared with the sham group, the abilities of learning and memory in the model group were significantly impaired (P<0.01), and the mRNA or protein expressions of CaM, CamkIV, HuB, HuC, HuD, HuB/D, HuC+HuD and Ferritin in CaM-CamkIV-CREB signal pathway were abnormally changed in model group. However, the three doses of SSF can differently ameliorate the impaired learning and memory and regulate the abnormal expressions of mRNA or protein in rats' CaM, CamkIV, HuB, HuC, HuD, HuB/D, HuC+HuD and Ferritin induced by composited Aß. CONCLUSION: The improvement of SSF on the learning and memory disorder induced by composited Aß is primarily derived from the positive regulation in the CaM-CamkIV-CREB signal pathway and activation in neuroplasticity.

The Molecular Mechanism of Scutellaria baicalensis Georgi Stems and Leaves Flavonoids in Promoting Neurogenesis and Improving Memory Impairment by the PI3K-AKT-CREB Signaling Pathway in Rats.

AIM: The aim of this study was to investigate the effect and molecular mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) in promoting neurogenesis and improving memory impairment induced by the PI3K-AKT-CREB signaling pathway. METHODS: Alzheimer's disease (AD) was induced in the male Wistar rats by intracerebroventricular injection of amyloid beta peptide 25-35 (Aß25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-ß1(RHTGF-ß1) (composited Aß). The Morris water maze was used to screen the successful establishment of the memory impairment model of rats. The screened successful model rats were randomly divided into a model group and three groups of three different doses of the drug (SSF). Rats in the drug group were treated with 35, 70, and 140 mg/kg of SSF for 43 days. The Eight-arm maze was used to measure the spatial learning and memory abilities of the rat, including working memory errors (WME) and reference memory errors (RME). Immunohistochemistry was used to detect the expression of BrdU, an indicator of neuronal proliferation, in the hippocampal gyrus of rats. The mRNA and protein expressions of TRKB, PI3K, AKT, P-AKT, and IGF2 in the PI3K-AKT-CREB signaling pathway in the hippocampus and cerebral cortex of the rats were determined by quantitative real-time PCR (qPCR) and Western blotting methods. RESULTS: Compared to the sham group, the spatial memory ability of rats with composited Aß was decreased, the number of WME and RME (P < 0.01) was increased, the expression of BrdU protein (P < 0.01) in the hippocampal gyrus was reduced, the mRNA and protein expression levels of TRKB, AKT, and IGF2 (P < 0.01, P < 0.05) in the hippocampus and cerebral cortex were lowered, and the mRNA expression level of PI3K (P < 0.01) in the cerebral cortex and the protein expression level of PI3K (P < 0.01) in the hippocampus were augmented. However, compared to the model group, the three-doses of SSF improved memory disorder induced by composited Aß, reduced the number of WME and RME, increased the expression of BrdU protein in the hippocampal gyrus, and differently regulated the mRNA and protein expressions in composited Aß rats. CONCLUSION: SSF improved memory impairment and neurogenesis disorder induced by composited Aß in rats by activating the PI3K-AKT-CREB signaling pathway and up-regulating the mRNA and protein expressions of TRKB, PI3K, AKT, CREB, and IGF2.