18 research outputs found

    Xanthohumol alleviates oxidative stress and impaired autophagy in experimental severe acute pancreatitis through inhibition of AKT/mTOR

    Get PDF
    Severe acute pancreatitis (SAP) is a lethal gastrointestinal disorder, yet no specific and effective treatment is available. Its pathogenesis involves inflammatory cascade, oxidative stress, and autophagy dysfunction. Xanthohumol (Xn) displays various medicinal properties,including anti-inflammation, antioxidative, and enhancing autophagic flux. However, it is unclear whether Xn inhibits SAP. This study investigated the efficacy of Xn on sodium taurocholate (NaT)-induced SAP (NaT-SAP) in vitro and in vivo. First, Xn attenuated biochemical and histopathological responses in NaT-SAP mice. And Xn reduced NaT-induced necrosis, inflammation, oxidative stress, and autophagy impairment. The mTOR activator MHY1485 and the AKT activator SC79 partly reversed the treatment effect of Xn. Overall, this is an innovative study to identify that Xn improved pancreatic injury by enhancing autophagic flux via inhibition of AKT/mTOR. Xn is expected to become a novel SAP therapeutic agent

    Study on the synthesis and characterization of CoTiO3 catalysts and their catalytic properties in Oxone activation for the degradation of tetracycline antibiotic in water

    No full text
    The chemical degradation of sulfate by activated Oxyone has the advantages of high degradation capacity, wide pH range and convenient transportation and storage, making it one of the most attractive advanced oxidation processes (AOPs). Besides, Co is the metal most capable of activating Oxone to produce sulfate. Therefore, it is critical to develop Co-based catalyst, an effective and recyclable heterogeneous catalyst, for activating Oxone to degrade tetracycline. In this study, CoTiO _3 was extensively investigated for the activation of Oxone to generate sulfate radicals and degrade tetracycline antibiotics. The results showed that more than 95% of tetracyclines could be degraded at the amount of CoTiO _3 catalyst of 0.02 g, the Oxone reagent concentration of 0.4 mmol l ^−1 , and the pH value of 7. The removal rate of tetracyclines could still reach more than 85% after the CoTiO _3 composite was repeatedly used for four consecutive cycles. These results indicate that CoTiO _3 /Oxone can be explored as an effective system for degrading long-lived organic pollutants

    Comprehensive Land Consolidation and Linear Cultural Heritage Protection, Utilization, Cohesion and Integration: A Case Study of the Gutian Section of the Meiguan Historical Trail, South China Historical Trail, Guangdong Province

    No full text
    The protection of historical and cultural heritage sites is the main focus of land space planning and use control. Its protection and utilization are important for promoting the revitalization of rural culture and building a pattern of historical and cultural protection, and are essential for the research on comprehensive land consolidation in recent years. The historical trail of South China is a linear cultural heritage site of Guangdong's historical development. Exploring the connotative relationship between comprehensive land consolidation and the protection and utilization of linear cultural heritage is conducive to enhancing their synergy and superposition. This study begins with a connotation analysis and trend analysis of comprehensive land consolidation and linear cultural heritage protection and utilization, taking the connecting line of the Gutian section of the ancient Meiguan historical trail of the Southern China historical trail in Guangdong Province as an example to explore the working relationship between comprehensive land consolidation and the protection and utilization of linear cultural heritage. It proposes a comprehensive land consolidation path for linear cultural heritage protection and utilization. Results showed that: 1) The problems faced by the protection of historical trails were closely related to the goal and content of comprehensive land consolidation; 2) The protection of historical trails and the comprehensive land consolidation could be integrated into the implementation of land space planning, rights and interests protection, policy incentives, public participation and landscape coordination to jointly promote the enhancement of land space value; 3) Focusing on the dimensions of development orientation, planning layout, engineering design, overall planning funds and service operation, it is necessary to constantly innovate the path of comprehensive land improvement across the region, and comprehensively promote the protection and utilization of rural cultural heritage. Guangdong Province can fully utilize the platform tools of comprehensive land consolidation in the protection of South China historical trail, achieve the connection and integration of ancient cultural protection and utilization with land consolidation projects, and establish a mutual feedback relationship in work, innovate and establish a working mechanism for the integration and development of comprehensive land consolidation and historical trail protection, which is conducive to the synergistic effect of rural revitalization and historical and cultural protection, better service and support for rural revitalization and high-quality development

    Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

    No full text
    Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD-/- mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway

    Table1_Calycosin attenuates renal ischemia/reperfusion injury by suppressing NF-κB mediated inflammation via PPARγ/EGR1 pathway.DOCX

    No full text
    Renal ischemia reperfusion injury (IRI) is a leading and common cause of acute kidney injury (AKI), and inflammation is a critical factor in ischemic AKI progression. Calycosin (CAL), a major active component of Radix astragali, has been reported to have anti-inflammatory effect in multiple organs. However, whether CAL can alleviate renal IRI and its mechanism remain uncertain. In the present study, a renal IRI model is established by bilateral renal pedicles occlusion for 35 min in male C57BL/6 mice, and the effect of CAL on renal IRI is measured by serum creatinine and pathohistological assay. Hypoxia/reoxygenation (H/R) stimulated human renal tubular epithelial cells HK-2 were applied to explore the regulatory mechanisms of CAL. Luciferase reporter assay and molecular docking were applied to identify the CAL’s target protein and pathway. In the mice with renal IRI, CAL dose dependently alleviated the renal injury and decreased nuclear factor kappa B (NF-κB) mediated inflammatory response. Bioinformatics analysis and experiments showed that early growth response 1 (EGR1) increased in mice with renal IRI and promoted NF-κB mediated inflammatory processes, and CAL dose-dependably reduced EGR1. Through JASPAR database and luciferase reporter assay, peroxisome proliferator-activated receptor γ (PPARγ) was predicted to be a transcription factor of EGR1 and repressed the expression of EGR1 in renal tubular epithelial cells. CAL could increase PPARγ in a dose dependent manner in mice with renal IRI and molecular docking predicted CAL could bind stably to PPARγ. In HK-2 cells after H/R, CAL increased PPARγ, decreased EGR1, and inhibited NF-κB mediated inflammatory response. However, PPARγ knockdown by siRNA transfection abrogated the anti-inflammation therapeutic effect of CAL. CAL produced a protective effect on renal IRI by attenuating NF-κB mediated inflammatory response via PPARγ/EGR1 pathway.</p
    corecore