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Cardiac hypertrophy and remodeling are among the major health challenges facing countries around the world today. Neohesperidin plays an important role in influencing cell apoptosis, cell growth, tumorigenesis and tumor microenvironment, but the mechanism and role of Neohesperidin in cardiac hypertrophy and remodeling caused by Angiotensin II has not been fully elucidated. This study used Angiotensin II to induce cardiac hypertrophy and cardiac remodeling in mice. Echocardiography was used to evaluate cardiac function, H&E and Masson trichrome staining were used to detect myocardial histological changes. Cardiac cell size was determined by WGA staining. The protein content of the signaling pathway was detected by Western blot, and the mRNA expression of fibrosis and hypertrophy markers was detected by qPCR. DHE staining was used to detect oxidative stress. We also observed the effect of Neohesperidin on Ang II-induced NRCMs. The results showed that neohesperidin can significantly inhibit Ang II-induced myocardial contractile dysfunction, cardiac hypertrophy, myocardial fibrosis, myocardial oxidative stress and inflammation. These results suggest that Neohesperidin can alleviate cardiac hypertrophy and remodeling caused by Ang II, and its mechanism may be related to the inhibition of multiple signaling pathways.Background Shenxiang Suhe Pill (SXSHP), a Chinese medicine formula, is widely used in clinic to treat coronary heart disease (CHD). However, due to the complex composition of SXSHP, its underlying mechanisms and pharmacodynamic properties are still unknown. In this paper, we try to define the compounds of SXSHP by dual-screening the active ingredients with anti-inflammation and antioxidant effects and predict its multi-target-pathway in CHD therapy using network pharmacology. Methods The chemical constituents in SXSHP were analyzed by UPLC/Q-TOF. Then, the active ingredients with the anti-inflammation and antioxidant effects were dual-screened by in vitro experiments. Ingenuity pathway analysis (IPA) was used to analyze and predict the potential targets and pathways of the anti-inflammatory and antioxidant effects of SXSHP. Results A total of 38 chemical constituents were identified in SXSHP, among which we screened six anti-inflammatory compounds luteolin, isorhamnetin-3-O-beta-d-glucoside, 4-hydroxy-3-methoxycinnamaldehyde, benzoic acid, kaempferol-3-O-glucuronide acid, and blumeatin; and five antioxidant compounds vanillin, eugenol, muscone, luteolin, and asiatic acid. IPA showed that eugenol, muscone, and 4-hydroxy-3-methoxycinnamaldehyde were closely related to the HIF-1 and IL-15 signaling pathways, which protect against oxidative stress and inflammation, respectively. Conclusions Among the 38 ingredients in SXSHP, the anti-inflammatory pharmacological effects of isorhamnetin-3-O-beta-d-glucoside, blumeatin and 4-hydroxy-3-methoxycinnamaldehyde were reported for the first time. According to the network pharmacology analysis, eugenol, 4-hydroxy-3-methoxycinnamaldehyde and muscone are involved in the antioxidant HIF-1 pathway and the anti-inflammatory IL-15 pathway, and that may be the mechanism of SXSHP in the treatment of CHD.Solasonine is a compound isolated from Solanum melongena that has anti-infection properties, and promotes neurogenesis. However, the use of solasonine for the treatment of hepatocellular carcinoma (HCC) has not yet been reported. So, the aim of this study was to assess the efficacy of solasonine for the treatment of HCC. The effects of solasonine were tested using the HCC cell lines HepG2 and HepRG. Metabolomics analysis was conducted to assess the effects of solasonine on tumor growth of nude mice xenografts using HepG2 cells. The data demonstrated that solasonine significantly suppressed proliferation of HepG2 and HepRG cells. A mouse xenograft model of HepG2 tumor formation confirmed that solasonine suppressed tumor volume and weight, and inhibited HCC cell migration and invasion, as determined with the Transwell and scratch wound assays. To further reveal the underlying regulatory mechanism, metabolomics analysis was performed. The results revealed the effects of solasonine on glutathione metabolism, including glutathione peroxidase 4 (GPX4) and glutathione synthetase (GSS). The glutathione-dependent lipid hydroperoxidase GPX4 prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death. Solasonine increased lipid ROS levels in HepG2 cells by suppression of GPX4 and GSS. However, the use of a ferroptosis inhibitor reversed solasonine-induced ROS production and cell apoptosis. Taken together, these results demonstrate that solasonine promotes ferroptosis of HCC cells via GPX4-induced destruction of the glutathione redox system.Microplastics (MPs) are persistent contaminants in aquatic environments. Microalgae, as the main phytoplankton and primary producers, usually co-exist with MPs. Despite previous studies that have proved the interaction of MPs and microalgae, it is largely unknown whether MPs can be uptake into cells of microalgae. In this study, both marine P. helgolandica var. tsingtaoensis and freshwater microalgae S. quadricauda were respectively exposed to 10 mg/L polystyrene microbeads with five diameter sizes 1.0, 2.0, 3.0, 4.0, and 5.0 μm. Confocal laser scanning and 3D image analysis showed that mean 24.0 % or 11.3 % cells of P. helgolandica var. AZD8186 tsingtaoensis contained 1.0 μm or 2.0 μm MPs after 72 h exposure. While mean 43.3 % or 15.3 % of S. quadricauda individuals engulfed 1.0 μm or 2.0 μm MPs within cells. But, none of 3.0-5.0 μm MPs were observed within algal cells. These results demonstrate the size-dependent cellular internalization of MPs in microalgae. Exposure to 1.0-2.0 μm PS MPs caused a significant reduction in the density of microalgae and influenced photosynthesis, which suggests cellular internalization of MPs can influence algal fertility and growth. This discovery first confirms cellular internalization of MPs in phytoplankton, of significance for the fate and eco-toxicity of MPs in the aquatic ecosystem.
My Website: https://www.selleckchem.com/products/azd8186.html
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