Dietary Dityrosine Induces Oxidative Stress and Mitochondrial-Lipid Imbalance in Mouse Liver via MiR-144-3p-Mediated Downregulation of Nrf2.

SCOPE: Dityrosine (DT) is a protein oxidation marker present in many high-protein foods, such as dairy and meat products. Chronic dietary intake of DT induces oxidative stress damage in the liver and impairs energy metabolism. This study aims to investigate the mechanisms underlying the effects of DT on disrupted hepatic energy metabolism. METHODS AND RESULTS: The study investigates hepatic lipid accumulation, redox status imbalance, mitochondrial dysfunction, and energy metabolism disorders in 4-week-old C57BL/6J mice after 35 days of DT (420 µg kg-1 body weight) treatment. Transcriptome sequencing and quantitative real-time PCR in HepG2 cells show that DT mainly acted via miR-144-3p. miR-144-3p targets immune responsive gene 1 (IRG1) and decreases the fumaric acid level in the tricarboxylic acid (TCA) cycle, thereby decreasing nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant activity. CONCLUSION: Administration of lycopene, a strong antioxidant, alleviates DT-induced damage in mice, confirming the involvement of the Nrf2 pathway in DT-induced abnormal hepatic lipid metabolism and energy homeostasis.

Does ambient air quality standard contribute to green innovation of enterprises in China? Implications for environmental protection and public health.

In the post-COVID-19 era, environmental pollution has been a serious threat to public health. Enterprises are in urgent need of enhancing green technology innovation as the main source of pollutant emissions, and it is necessary for governments to support green innovation of enterprises to reduce pollutant emissions and promote public health. In this context, this paper investigates whether the Ambient Air Quality Standard (AAQS) implemented in 2012 in China contributes to green innovation of enterprises, to provide implications for environmental protection and public health. By using panel data of Chinese A-share listed companies from 2008 to 2020, this study adopts the difference-in-difference model to analyze the policy impact of environmental regulation on green innovation of enterprises and its internal mechanism. The results show that AAQS has significantly improved the green innovation of enterprises. Furthermore, AAQS affects the green innovation of enterprises by virtue of two mechanism paths: compliance cost effect and innovation offset effect. On the one hand, AAQS leads to an increase in production costs of enterprises, thus inhibiting green innovation activities of enterprises. On the other hand, AAQS encourages enterprises to increase R&D investment in green technology, thus enhancing their green innovation. In addition, the impact of AAQS on firms' green innovation has heterogeneous characteristics. Our findings not only enrich the studies of environmental regulation and green innovation of enterprises but also provide policymakers in China and other developing countries with implications for environmental protection and public health improvement.

Whether Green Finance Improves Green Innovation of Listed Companies-Evidence from China.

Facing the intensification of global carbon emissions and the increasingly severe pressure of environmental pollution, listed companies urgently need to promote green innovation, achieve green transformation, and alleviate environmental problems. Green finance policy has played a significant role as a financial strategy for environmental governance in affecting green innovation level over the years. In this context, taking the green finance reform and innovation pilot zone (GFRIPZ) implemented in 2017 in China as a quasi-natural experiment, this paper analyzes the impact of green finance policy on green innovation level of listed companies by the difference-in-difference model. Based on the data of Chinese A-share listed companies from 2008 to 2020, the results of empirical analysis show that green finance significantly promotes green innovation of listed companies. The effect is profound on green utility model patents, but less pronounced on green invention patents. Among all these pilot zones, the policy effects of GFRIPZ ranked in descending order are Zhejiang, Guangdong, Jiangxi, Guizhou, and Xinjiang. In addition, green finance has a more significant impact on heavy-polluting industries, large and state-owned enterprises, and listed companies located in the eastern region. Furthermore, the effects of industry heterogeneity ranked in descending order are energy, manufacturing, processing, and engineering industry, while it is not obvious in the service industry. Mechanism analysis suggests that the effect is driven by a reduction in the cost of debt financing and an increase in the long-term debt ratio. The findings provide implications for policymakers to promote the level of green innovation and environmental governance. Therefore, policymakers should support the long-term creative development of green invention patents by reducing the cost of debt financing and increasing the long-term debt ratio and consider the heterogeneous characteristics of listed companies when formulating green finance policies.

Sodium butyrate protects against oxidative stress in high-fat-diet-induced obese rats by promoting GSK-3ß/Nrf2 signaling pathway and mitochondrial function.

Sodium butyrate (NaB), obtained by fermenting dietary fiber via intestinal microflora, was recently shown to improve the activity of some antioxidant enzymes in vivo. This study aims to investigate the term changes of mitochondrial energy metabolism and redox homeostasis in skeletal muscles and clarify the regulatory mechanism and dose effect of NaB on skeletal muscle. Male Sprague-Dawley rats were divided into the control group, obesity-prone (OP) group and obesity-resistant (OR) group based on the gain of body weight after 8 weeks' of feeding high-fat diet (HFD), followed by sacrificing rats at the end of 20th week. NaB intervention (12 weeks) could effectively reduce the body weight of rats in the OP and OR groups. NaB also mediated upregulation of antioxidant enzyme activity and GSH/GSSG ratio, while reducing reactive oxygen species (ROS) levels and malondialdehyde (MDA) content. At the molecular level, NaB upregulated Pi3k, Nrf2, Nqo-1, and Ho-1, but downregulated Gsk-3ß mRNA expression by regulating the Nrf2 antioxidant pathway to enhance tissue antioxidant capacity. At the same time, NaB intervention significantly upregulated Glut4, Irs-1, Pdx1, and MafA, expression in gastrocnemius muscles of OP and OR rats, and elevated insulin secretion and muscle insulin sensitivity. Thus, NaB activates antioxidant pathway, improves the antioxidant capacity of obese rat tissues and promotes glucose metabolism. PRACTICAL APPLICATIONS: This study found that obesity-prone and obesity-resistant rats have differences in mitochondrial redox homeostasis and energy metabolism in tissues. Meanwhile, sodium butyrate can effectively promote muscle protein synthesis, increase insulin sensitivity, and promote glucose metabolism in obesity rats. Thus, sodium butyrate supplementation or increasing intestinal butyrate production (e.g., by consuming foods rich in dietary fiber) is a potential means of improving the body's glucose metabolism and obesity profile.