Stroke is a major cause of death and adult disability. However, therapeutic options remain limited. Numerous pathways underlie acute responses of brain tissue to stroke. Early events following ischemic damage include reactive oxygen species (ROS)-mediated oxidative stress and glutamate-induced excitotoxicity, both of which contribute to rapid cell death within the infarct core. A subsequent cascade of inflammatory events escalates damage progression. This review explores potential neuroprotective strategies for targeting key steps in the cascade of ischemia–reperfusion (I/R) injury. NADPH oxidase (NOX) inhibitors and several drugs currently approved by the U.S. Food and Drug Administration including glucose-lowering agents, antibiotics, and immunomodulators, have shown promise in the treatment of stroke in both animal experiments and clinical trials. Ischemic conditioning, a phenomenon by which one or more cycles of a short period of sublethal ischemia to an organ or tissue protects against subsequent ischemic events in another organ, may be another potential neuroprotective strategy for the treatment of stroke by targeting key steps in the I/R injury cascade.
Increasing amounts of evidence show that insulin can activate different insulin signaling pathways to promote breast cancer growth and invasion. miR-29a plays crucial roles in decreasing glucose-stimulated insulin secretion, as well as in regulating breast cancer cell proliferation and EMT. However, the mechanism responsible for the regulatory effects of miR-29a on breast cancer growth and invasion and the relationship between these effects and insulin signaling remains unclear. Herein, we showed that human insulin increased miR-29a expression in ER-positive breast cancer cells and that miR-29a facilitated the ability of insulin to promote breast cancer cell proliferation and migration. We found that miR-29a-induced cell proliferation and metastasis acceleration occurred primarily through ERK phosphorylation. The IGF-1R is the upstream target gene of miR-29a, while CDC42 and p85α are the downstream target genes of miR-29a. These results have provided us with information regarding the molecular mechanisms by which hyperinsulinemia promotes breast cancer occurrence and development and thus leads to a poor prognosis in breast cancer patients and indicate that miR-29a plays an important role in breast cancer development and invasion.
PurposeThe engagement–addiction dilemma has been commonly observed in the information technology (IT) industry. However, this issue has received limited research attention in the information system (IS) discipline. Drawing on the stimulus–organism–response (SOR) framework, this study explores the engagement–addiction dilemma in the use of mobile games and highlights the impacts of game design features, namely, mobile user interface and mobile game affordance.Design/methodology/approachThe research model was empirically validated using a longitudinal survey data from 410 mobile game users in China.FindingsThe empirical results offer several key findings. First, mobile user interface and mobile game affordance positively affect telepresence and social presence, which lead to meaningful engagement and mobile game addiction. Second, a high-quality of mobile user interface positively moderates the effects of mobile game affordance on telepresence and social presence.Originality/valueThis study contributes to the literature by theorizing and empirically testing the impacts of game design features on the engagement-addiction dilemma.
Apigenin, identified as 4′, 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 μg/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1β (IL-1β), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN.
Objectives Andrographlide sulphonate E, namely sodium 9‐dehydro‐17‐hydro‐andrographolide‐19‐yl sulphate, was one of the major ingredients of Xiyanping injection. The present study aimed to demonstrate its suitability as a reference standard for use of quality control of this traditional Chinese medicine preparation made from andrographlide that has been widely used to treat various infectious diseases. Methods The stable crystals were prepared for unambiguous elucidation of the chemical structure by comprehensive spectral and thermal analysis. The anti‐inflammatory effects were investigated using in vitro and in vivo methods, and the potential allergenic risk related with safety was evaluated by in silico molecular docking analysis. Key findings The dihydrated sulphonate derivative could be present as orthorhombic crystals with stable three‐dimensional supramolecular structure, providing it the favourable physico‐chemical stability as reference substance. It exhibited potent anti‐inflammatory activity both in vitro and in vivo, suggesting the potency responsible for clinic efficacy of Xiyanping. Molecular docking further demonstrated its low risk of allergic reaction, as well as the proposed mechanism of anaphylactic effect of andrographolide analogues. Conclusions Dihydrated sodium 9‐dehydro‐17‐hydro‐andrographolide‐19‐yl sulphate may be the ideal reference standard for use in quality control of Xiyanping.
<b><i>Objective:</i></b> The purpose of this meta-analysis is to evaluate the safety and efficacy of tirofiban during endovascular treatment (EVT) for acute ischemic stroke (AIS) patients. <b><i>Methods:</i></b> We systematically searched PubMed, Embase, Web of Science, and CENTRAL (Cochrane Central Register of Controlled Trials) databases for randomized controlled trials and cohort studies (published before May 1, 2020; no language restrictions) comparing tirofiban administration to blank control during EVT in patients with AIS. Our primary end points were the 3-month functional outcome, recanalization rate, symptomatic intracerebral hemorrhage, and 3-month mortality. <b><i>Results:</i></b> The incidence of 3-month modified Rankin Scale (mRS) 0–2 score of the tirofiban group was higher than that of the control group (odds ratio [OR] = 1.27, 95% CI [1.09, 1.48], <i>p</i> = 0.002) with heterogeneity (<i>I</i><sup>2</sup> = 34%, <i>p</i> = 0.11). Data pooled from the 6 studies describing the details of retriever stent in EVT revealed that tirofiban was associated with higher incidence of 3-month mRS 0–2 score (OR = 1.48, 95% CI [1.11, 1.96], <i>p</i> = 0.007). The recanalization rate was higher in the tirofiban group compared to the control group (OR = 1.66, 95% CI [1.16, 2.39], <i>p</i> = 0.006). There were no statistically significant differences in the incidence of symptomatic intracranial hemorrhage (OR = 0.97, 95% CI [0.73, 1.31], <i>p</i> = 0.86) and intracranial hemorrhage (OR = 1.08, 95% CI [0.59, 1.97], <i>p</i> = 0.80) between tirofiban and non-tirofiban group. Besides, the tirofiban administration was associated with lower mortality (OR = 0.75, 95% CI [0.62, 0.91], <i>p</i> = 0.003). <b><i>Conclusions:</i></b> The application of tirofiban in EVT of AIS may improve functional outcomes and reduce mortality at 3 months. Besides, tirofiban does not seem to increase the risk of symptomatic intracranial hemorrhage and intracranial hemorrhage, either in the anterior or posterior circulation stroke.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.