PO-145 Effects of HIF-1α on Nrf2-ARE antioxidant signal in mice skeletal muscle after acute exhaustive exercise

Objective Hypoxia or exercise could lead to oxidative stress. Hypoxia inducible factor-1 (HIF-1) is an oxygen sensor and the expression of its α subunit can be regulated by hypoxia. NF-E2-related factor 2 (Nrf2) is an important modifier of cellular responses to oxidative stress. A major mechanism in defense oxidative stress is the activation of the Nrf2-ARE antioxidant pathway. But whether the increase of HIF-1α could affect the Nrf2-ARE antioxidant signal, and further influence the oxidative stress status in vivo remains unknown. In this study, we wished to examine the effect of HIF-1α on Nrf2-ARE antioxidant pathway in mice skeletal muscle after acute exhaustion exercise. Methods HIF-1α high expression (H) and C57BL/6J mice(W) were used at 20 respectively and each kind of mice were randomly divided into two groups: control (C) and exercise (E). The treadmill exercise was preformed at the acute exhaustion exercise. On the day of acute exercise, mice allocated to perform treadmill running were subject to 5% incline and 5min at 10m/min, and then increased 3m/min every 3 minutes. Mice were sacrificed at the indicated time points following treadmill running.Nrf2, phosphor-Nrf2 (Ser40), nuclear Nrf2 protein were measured by Western Blot and Nrf2-ARE binding activity, the mRNA and proetin levels of Nrf2 target genes, key antioxidant enzymes (SOD1, SOD2, CAT, NQO-1) and ROS level, were also measured in skeletal muscles after the interventions. Results (1)The results showed that compared with WC, RNA and protein expression level of Nrf2 were increased in HC skeletal muscles. Nrf2-ARE binding activity, Nrf2 target gene SOD1, SOD2, NQO-1 mRNA expression and NQO-1 protein expression were also increased in HC skeletal muscles. Meanwhile, ROS level in HC skeletal muscles decreased significantly. (2) After the acute exhaustion exercise, high HIF-1α expression mice (HE) had higher expression of p-Nrf2(Ser 40) and nuclear Nrf2 protein than the wide type mice(WE). The mRNA expression of SOD1 and mRNA /protein of NQO-1 in HE increased as well. In contrast, ROS level decreased significantly in HE muscles. ConclusionsThe result indicated the proper high expression of HIF-1α could promote the antioxidant capacity of skeletal muscle in mice through Nrf2-ARE pathway

Near work, outdoor activity, and myopia in children in rural China: The Handan Offspring Myopia Study

Dataset. (XLS 112 kb

Structural Attack to Anonymous Graph of Social Networks

With the rapid development of social networks and its applications, the demand of publishing and sharing social network data for the purpose of commercial or research is increasing. However, the disclosure risks of sensitive information of social network users are also arising. The paper proposes an effective structural attack to deanonymize social graph data. The attack uses the cumulative degree of n-hop neighbors of a node as the regional feature and combines it with the simulated annealing-based graph matching method to explore the nodes reidentification in anonymous social graphs. The simulation results on two social network datasets show that the attack is feasible in the nodes reidentification in anonymous graphs including the simply anonymous graph, randomized graph and k-isomorphism graph

Biomimetic nanotherapies: red blood cell based core-shell structured nanocomplexes for atherosclerosis management

Cardiovascular disease is the leading cause of mortality worldwide. Atherosclerosis, one of the most common forms of the disease, is characterized by a gradual formation of atherosclerotic plaque, hardening, and narrowing of the arteries. Nanomaterials can serve as powerful delivery platforms for atherosclerosis treatment. However, their therapeutic efficacy is substantially limited in vivo due to nonspecific clearance by the mononuclear phagocytic system. In order to address this limitation, rapamycin (RAP)‐loaded poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles are cloaked with the cell membrane of red blood cells (RBCs), creating superior nanocomplexes with a highly complex functionalized bio‐interface. The resulting biomimetic nanocomplexes exhibit a well‐defined “core–shell” structure with favorable hydrodynamic size and negative surface charge. More importantly, the biomimetic nature of the RBC interface results in less macrophage‐mediated phagocytosis in the blood and enhanced accumulation of nanoparticles in the established atherosclerotic plaques, thereby achieving targeted drug release. The biomimetic nanocomplexes significantly attenuate the progression of atherosclerosis. Additionally, the biomimetic nanotherapy approach also displays favorable safety properties. Overall, this study demonstrates the therapeutic advantages of biomimetic nanotherapy for atherosclerosis treatment, which holds considerable promise as a new generation of drug delivery system for safe and efficient management of atherosclerosis

Penetration of the blood-brain barrier and anti-tumor effect of a novel PLGA-lysoGM1/DOX micelles drug delivery system

Effective treatment of glioma and other central nervous system (CNS) diseases is hindered by the presence of the blood-brain barrier (BBB). A novel nano-delivery vehicle system comprised of PLGA-lysoGM1/DOX micelles was developed to across the BBB for CNS administration. We have shown that Doxorubicin (DOX) as a model drug encapsulated in PLGA-lysoGM1 micelles, can achieve up to 3.8% loading efficiency and 61.6% encapsulation efficiency by the orthogonal test design. Our in vitro experiments demonstrate that PLGA-lysoGM1/DOX micelles have a slow and sustainable drug release under physiological conditions and exhibit a high cellular uptake through the macropinocytosis and the autophagy/lysosomal pathways. In vivo experimental studies in zebrafish and mice confirmed that PLGA-lysoGM1/DOX micelles could across the BBB and specifically accumulated in the brain. Moreover, an excellent anti-glioma effect presented in intracranial glioma‐bearing rat. Therefore, PLGA-lysoGM1/DOX micelles not only effectively acrossed the BBB, but our results suggest it has a great potential for anti-glioma therapy and other central nervous system diseases

Effects of carbohydrate drinks ingestion on executive function in athletes: a systematic review and meta-analysis

BackgroundCarbohydrates are often used as boosters for endurance and high-intensity exercise. However, it is unclear whether carbohydrate drinks intake before or during exercise can affect specific domains of cognitive function, such as Executive Function (EF).MethodsFollowing the guidance of PRISMA 2020, we searched six major databases including PubMed, WOS, SPORTDiscus, Cochrane, Embase, and Scopus. Outcomes were presented in the form of Reaction Time (RT), Accuracy (ACC), and Scores (Score) for performing EF tests. Effect sizes were calculated from the test results of EF and expressed as standardized mean differences (SMDs). After analyzing the overall results, we performed subgroup analyses based on the athletes’ program characteristics.ResultsAfter retrieving a total of 5,355 articles, ten randomized controlled trials (RCTs) were identified and included in this review. The overall results showed that the intake of carbohydrate drinks before or during exercise did not have a significant effect on the reduction of EF after exercise (ACC (−0.05 [−0.27, 0.18]); RT (−0.18 [−0.45, 0.09]); Score (0.24 [−0.20, 0.68])). The subgroup analyses based on open skill sports and close skill sports also showed invalid results, but the results of RT ended up with different preference (ACC of open skill sports athletes (−0.10 [−0.34, 0.14]); RT of open skill athletes (−0.27 [−0.60, 0.07]); RT of close skill athletes (0.29 [−0.24, 0.82])).ConclusionThe intake of 6–12% of single or mixed carbohydrates before or during exercise was not significantly effective in reducing the decline in EF after exercise. Our findings may have been influenced by the type of intervention, dose, mode of administration, or individual variability of the included subjects