Bicyclol attenuates high fat diet-induced non-alcoholic fatty liver disease/non-alcoholic steatohepatitis through modulating multiple pathways in mice

Introduction: The pathological progression of non-alcoholic fatty liver disease (NAFLD) is driven by multiple factors, and non-alcoholic steatohepatitis (NASH) represents its progressive form. In our previous studies, we found that bicyclol had beneficial effects on NAFLD/ NASH. Here we aim to investigate the underlying molecular mechanisms of the bicyclol effect on NAFLD/NASH induced by high-fat diet (HFD) feeding.Methods: A mice model of NAFLD/NASH induced by HFD-feeding for 8 weeks was used. As a pretreatment, bicyclol (200 mg/kg) was given to mice by oral gavage twice daily. Hematoxylin and eosin (H&E) stains were processed to evaluate hepatic steatosis, and hepatic fibrous hyperplasia was assessed by Masson staining. Biochemistry analyses were used to measure serum aminotransferase, serum lipids, and lipids in liver tissues. Proteomics and bioinformatics analyses were performed to identify the signaling pathways and target proteins. Data are available via Proteome X change with identifier PXD040233. The real-time RT-PCR and Western blot analyses were performed to verify the proteomics data.Results: Bicyclol had a markedly protective effect against NAFLD/NASH by suppressing the increase of serum aminotransferase, hepatic lipid accumulation and alleviating histopathological changes in liver tissues. Proteomics analyses showed that bicyclol remarkably restored major pathways related to immunological responses and metabolic processes altered by HFD feeding. Consistent with our previous results, bicyclol significantly inhibited inflammation and oxidative stress pathway related indexes (SAA1, GSTM1 and GSTA1). Furthermore, the beneficial effects of bicyclol were closely associated with the signaling pathways of bile acid metabolism (NPC1, SLCOLA4 and UGT1A1), cytochrome P450-mediated metabolism (CYP2C54, CYP3A11 and CYP3A25), biological processes such as metal ion metabolism (Ceruloplasmin and Metallothionein-1), angiogenesis (ALDH1A1) and immunological responses (IFI204 and IFIT3).Discussion: These findings suggested that bicyclol is a potential preventive agent for NAFLD/NASH by targeting multiple mechanisms in future clinical investigations

Metabolite analysis reveals distinct spatio-temporal accumulation of anthocyanins in two teinturier variants of cv. ‘Gamay’ grapevines (Vitis vinifera L.)

In most red grape cultivars, anthocyanins accumulate exclusively in the berry skin, while ‘teinturier’ cultivars also accumulate anthocyanins in the pulp. Here, we investigated the teinturier cvs. ‘Gamay de Bouze’ and ‘Gamay Fréaux’ (two somatic variants of the white-fleshed cv. ‘Gamay’) through metabolic and transcript analysis to clarify whether these two somatic variants have the same anthocyanin accumulation pattern in the skin and pulp, and whether primary metabolites are also affected. The skin of the three cultivars and the pulp of ‘Gamay de Bouze’ begun to accumulate anthocyanins at the onset of berry ripening. However, the pulp of ‘Gamay Fréaux’ exhibited a distinct anthocyanin accumulation pattern, starting as early as fruit set with very low level of sugars. The highest level of anthocyanins was found in ‘Gamay Fréaux’ skin, followed by ‘Gamay de Bouze’ and ‘Gamay’. Consistently, the transcript abundance of genes involved in anthocyanin biosynthesis were in line with the anthocyanin levels in the three cultivars. Despite no evident differences in pulp sugar content, the concentration of glucose and fructose in the skin of ‘Gamay Fréaux’ was only half of those in the skin of ‘Gamay’ and ‘Gamay de Bouze’ throughout all berry ripening, suggesting an uncoupled accumulation of sugars and anthocyanins in ‘Gamay Fréaux’. The study provides a comprehensive view of metabolic consequences in grape somatic variants and the three almost isogenic genotypes can serve as ideal reagents to further uncover the mechanisms underlying the linkage between sugar and anthocyanin accumulation.This research was supported partly by the National Key R&D Program of China (2018YFD1000200) and was conducted as part of the LIA INNOGRAPE International Associated Laboratory.Peer reviewe

Berberine Ameliorates High Glucose-Induced Cardiomyocyte Injury via AMPK Signaling Activation to Stimulate Mitochondrial Biogenesis and Restore Autophagic Flux

Background: Type II diabetes (T2D)-induced cardiomyocyte hypertrophy is closely linked to the impairment of mitochondrial function. Berberine has been shown to be a promising effect for hypoglycemia in T2D models. High glucose-induced cardiomyocyte hypertrophy in vitro has been reported. The present study investigated the protective effect and the underlying mechanism of berberine on high glucose-induced H9C2 cell line.Methods: High glucose-induced H9C2 cell line was used to mimic the hyperglycemia resulting in cardiomyocyte hypertrophy. Berberine was used to rescue in this model and explore the mechanism in it. Confocal microscopy, immunofluorescence, RT-PCR, and western blot analysis were performed to evaluate the protective effects of berberine in high glucose-induced H9C2 cell line.Results: Berberine dramatically alleviated hypertrophy of H9C2 cell line and significantly ameliorated mitochondrial function by rectifying the imbalance of fusion and fission in mitochondrial dynamics. Furthermore, berberine further promoted mitogenesis and cleared the damaged mitochondria via mitophagy. In addition, berberine also restored autophagic flux in high glucose-induced cardiomyocyte injury via AMPK signaling pathway activation.Conclusion: Berberine ameliorates high glucose-induced cardiomyocyte injury via AMPK signaling pathway activation to stimulate mitochondrial biogenesis and restore autophagicflux in H9C2 cell line

Initiator or Intermediary? A Case Study on Network Relation of Environmental Regulatory Capture in China

Behind the environmental regulatory capture (ERC) lies a complex network of interactions and interests. Identifying the roles of stakeholders in the ERC network and their behavioral motives can illuminate the mechanism of ERC incidents, and provide policy recommendations for reducing other types of regulatory capture. Drawing on the regulatory capture and principal-agent theories, this study develops a triple-layer principal-agent model of environmental regulation practices in China. We further conduct a social network analysis (SNA) on the ERC case in the Environmental Protection Bureau (EPB) of Bobai County, Guangxi Province, China to illustrate the hidden interactions and interest transmission structure among stakeholders in ERC. The results show that the ERC presents obvious characteristics of concealment and complexity, and individual capture often evolves into collective capture. Different stakeholders are in different positions and play different roles in the network. The environmental regulatory authority, the commissioned regulatory agency, and the agency of enterprises form the core power circle of the ERC network, in which the first two play the role of intermediary and the latter acts as an initiator. They together occupy the structural hole position and dominate the evolution of the ERC network. Peripheral structure stakeholders play the role of “bridge” and profit from the expanding ERC network. It is recommended that the principle of decentralization and the balance of power must be taken into consideration. Quantitative analysis methods such as SNA should be applied to clarify accountability when punishing responsible persons. More subjects are also encouraged to participate in environmental regulations and report illegal acts actively. Finally, a blacklist system should be established in the field of environmental protection for regulating the professional and social morality of all parties

Comparative analyses of polyphenolic composition of Fragaria spp. color mutants

White-fruited mutants of Fragaria vesca, and one of F. x ananassa, were studied to determine the identity and quantity of major flavonols (FVLs), flavan-3-ols (FV3Ls), hydroxycinnamic acids (HCAs), and ellagic acid (EA)-derived compounds, by using HPLC-MS. The content of 22 compounds across the major groups were used to assess the possibility of unique mutations among the mutant gentoypes. Total HCAs were lower in the white than the red cultivars of both species, except for 2 white F. vesca cultivars. Total FVLs were comparable in white fruit of both species, although a red F. x ananassa had more than a red F. vesca. Total FV3Ls were higher in red than white cultivars of both species. Total EA-derived content was generally higher in white than in red F. vesca. Principal component analysis and a combined heatmap and hierarchical cluster analysis clearly discriminated among the five white F. vesca genotypes

Comparative analysis of the dynamic proteomic profiles in berry skin between red and white grapes (Vitis vinifera L.) during fruit coloration

The aim of this study was to deepen our understanding of the proteomic profiles related to skin coloration at the whole proteome level through the analysis of multiple protein spots. A comparative proteomics analysis was conducted on the berry skins of red and white progeny derived from a single cross, 'Jingxiu' (red) x 'Muscat of Alexandria' (white), to minimize genetic background differences. Among the 1000-1800 spots assessed, the levels of 57, 70 and 26 proteins were lower in the skins of white progeny, compared to the skins of red progeny at about two weeks before veraison, at veraison and at maturity, respectively. Alternatively, the levels of 54, 50 and 23 proteins were higher at about two weeks before veraison, at veraison and at maturity, respectively. The levels of proteins involved in anthocyanin biosynthesis, especially UFGT and AOMT, were lower in the skins of white progeny at veraison and at maturity, and the levels of most proteins involved in amino acid metabolism were found to be lower before veraison. Almost all differentially accumulated proteins involved in energy production were found before and at veraison, while there was no difference detected in the levels of glycolysis, tricarboxylic acid cycle and photosynthesis between the skins of red and white progeny. The differential accumulation of enzyme proteins involved in anthocyanin synthesis had a decisive influence on the different skin colorization of red and white progeny. Many proteins related to metabolism and energy production were also differentially accumulated. In addition, many differences in the skin proteomes of white and red progeny were apparent before veraison, i.e. before skins developed coloration. (C) 2013 Elsevier B.V. All rights reserved

Proteomic analysis of grape berry skin responding to sunlight exclusion

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