Astaxanthin promotes mitochondrial biogenesis and antioxidant capacity in chronic high-intensity interval training

Purpose: Reactive oxygen and nitrogen species are required for exercise-induced molecular adaptations; however, excessive exercise may cause cellular oxidative distress. We postulate that astaxanthin (ASX) can neutralize oxidative distress and stimulate mitochondrial biogenesis in high-intensity exercise-trained mice. Methods: Six-week-old mice (n = 8/group) were treated with ASX (10 mg/kg BW) or placebo. Training groups participated in 30 min/day high-intensity interval training (HIIT) for 6 weeks. Gastrocnemius muscle was collected and assayed following the exercise training period. Results: Compared to the HIIT control mice, the ASX-treated HIIT mice reduced malonaldehyde levels and upregulated the expression of Nrf2 and FOXO3a. Meanwhile, the genes NQO1 and GCLC, modulated by Nrf2, and SOD2, regulated by FOXO3a, and GPx4, were transcriptionally upregulated in the ASX-treated HIIT group. Meanwhile, the expression of energy sensors, AMPK, SIRT1, and SIRT3, increased in the ASX-treated HIIT group compared to the HIIT control group. Additionally, PGC-1α, regulated by AMPK and SIRT1, was upregulated in the ASX-treated HIIT group. Further, the increased PGC-1α stimulated the transcript of NRF1 and Tfam and mitochondrial proteins IDH2 and ATP50. Finally, the ASX-treated HIIT mice had upregulations in the transcript level of mitochondrial fusion factors, including Mfn1, Mfn2, and OPA1. However, the protein level of AMPK, SIRT1, and FOXO3a, and the transcript level of Nrf2, NQO1, PGC-1α, NRF1, Mfn1, Mfn2, and OPA1 decreased in the HIIT control group compared to the sedentary control group. Conclusion: Supplementation with ASX can reduce oxidative stress and promote antioxidant capacity and mitochondrial biogenesis during strenuous HIIT exercise in mice.</p

High-dose astaxanthin supplementation suppresses antioxidant enzyme activity during moderate-intensity swimming training in mice

Exercise-induced reactive oxygen and nitrogen species are increasingly considered as beneficial health promotion. Astaxanthin (ASX) has been recognized as a potent antioxidant suitable for human ingestion. We investigated whether ASX administration suppressed antioxidant enzyme activity in moderate-intensity exercise. Seven-week-old male C57BL/6 mice (n = 8/group) were treated with ASX (5, 15, and 30 mg/kg BW) combined with 45 min/day moderate-intensity swimming training for four weeks. Results showed that the mice administrated with 15 and 30 mg/kg of ASX decreased glutathione peroxidase, catalase, malondialdehyde, and creatine kinase levels in plasma or muscle, compared with the swimming control group. Beyond that, these two (15 and 30 mg/kg BW) dosages of ASX downregulated gastrocnemius muscle erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Meanwhile, mRNA of Nrf2 and Nrf2-dependent enzymes in mice heart were also downregulated in the ASX-treated groups. However, the mice treated with 15 or 30 mg/kg ASX had increased constitutive nitric oxidase synthase and superoxide dismutase activity, compared with the swimming and sedentary control groups. Our findings indicate that high-dose administration of astaxanthin can blunt antioxidant enzyme activity and downregulate transcription of Nrf2 and Nrf2-dependent enzymes along with attenuating plasma and muscle MDA

WAP four-disulfide core domain protein 2 promotes metastasis of human ovarian cancer by regulation of metastasis-associated genes.

BACKGROUND: WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. METHODS: In this study, we evaluated the role of WFCD2 in tumor mobility, invasion and metastasis of ovarian cancer in clinical tissue and in ovarian cancer cells, both in vitro and in vivo. RESULTS: Our results revealed WFCD2 was overexpressed in ovarian tissues, and the expression level of WFCD2 was associated with metastasis and lymph node metastasis. Higher expression of WFCD2 was also observed in aggressive HO8910-PM cells than in HO8910 cells, and WFCD2 knockdown halted cell migration, invasion, tumorigenicity and metastasis in ovarian cancer cells, both in vitro and in vivo. Knockdown of WFDC2 induced the down-regulation of ICAM-1, CD44, and MMP2. CONCLUSION: In summary, our work demonstrates that WFCD2 promotes metastasis in ovarian cancer. These findings suggest that WFCD2 plays a critical role in promoting metastasis and may constitute a potential therapeutic target of ovarian cancer

Nonlinear magnetic-coupled flutter-based aeroelastic energy harvester: modeling, simulation and experimental verification

Aeroelastic energy harvesting can be used to power wireless sensors embedded into bridges, ducts, high-altitude buildings, etc. One challenging issue is that the wind speed in some application environments is low, which leads to an inefficiency of aeroelastic energy harvesters. This paper presents a novel nonlinear magnetic-coupled flutter-based aeroelastic energy harvester (FAEH) to enhance energy harvesting at low wind speeds. The presented harvester mainly consists of a piezoelectric beam, a two-dimensional airfoil, two tip magnets and two external magnets. The function of magnets is to reduce the cut-in wind speed of the FAEH and enhance energy harvesting performance at low wind speeds. A theoretical model is deduced based on Hamilton's principle, theory of aeroelasticity, Kirchhoff's laws and experimental measurements, etc. A good agreement is found between numerical simulation and experimental results, which verifies the accuracy of the theoretical model. Stability analysis is provided to determine the characteristics of the presented harvester. More importantly, it is numerically and experimentally verified that the presented harvester has a much lower cut-in wind speed (about 1.0 m s−1) and has a better energy harvesting performance at a low wind speed range from 1.0 m s−1 to 2.9 m s−1, when compared with traditional FAEHs

Effect of high-elasticity anti-rutting additive on viscoelastic behavior of asphalt binder and its modification mechanism

High-elasticity anti-rutting additives, one of the most promising modifiers of asphalt mixtures, were commonly utilized for mixtures by mixing with aggregates directly. However, their interaction with the asphalt binder and their modification mechanism remain unclear. Accordingly, to understand the rheological behavior of asphalt binder modified with high-elasticity anti-rutting additives, three additives were added into asphalt binder to prepare high-elasticity modified asphalts (HEMAs) via a high-speed shear mixer, and the typical attributes of viscoelastic properties were investigated by the rotational viscosity (RV) test, frequency sweep test, as well as bending beam rheometer test. Following that, the relation between the macro-rheological behavior and microscopic mechanism was incorporated by applying Fourier transform infrared spectroscopy (FTIR), atomic force microscope (AFM), and fluorescence microscopy (FM) analysis, respectively. Results indicate that the incorporation of high-elasticity additives into base asphalt causes a remarkable increase in RV along with a decline in temperature susceptibility. Likewise, a higher proportion of elasticity behavior is indicated for HEMAs, for which the wider temperature range of elasticity dominance also occurs. Regarding modification mechanism, the interaction between the asphalt and additives is physical co-blending, without new characteristic peaks appearing in FTIR spectrum. The AFM test reveals the grouping effect of “bee-structures” conduces the agglomeration of wax crystals and macromolecular components, thus increasing the elasticity and RV of HEMAs. However, the poor compatibility between the ARA-U additive and asphalt leads to unsatisfactory low-temperature performance. Significantly, a large area percentage of “sea-island structure” implies better compatibility of ARA-N, which strongly confirms the existence of the plateau region in master curve. It recommends employing anti-rutting additives that are compatible with the asphalt and enable moderately increase its elasticity, which ensure considerable entanglement and sufficient network in the asphalt-additive system, so that balanced performance can be achieved for the asphalt binder

Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses

Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear.Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage.Results: Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-β, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α.Conclusion: QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage

Table3_Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses.XLSX

Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear.Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage.Results: Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-β, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α.Conclusion: QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage.</p

Table4_Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses.XLSX

Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear.Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage.Results: Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-β, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α.Conclusion: QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage.</p