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11.
Mitsugu Watanabe Hirotoshi Fuda Shigeki Jin Toshihiro Sakurai Shu-Ping Hui Seiji Takeda Takayuki Watanabe Takao Koike Hitoshi Chiba 《Food chemistry》2012
3,5-Dihydroxy-4-methoxybenzyl alcohol (DHMBA), an antioxidant isolated from the Pacific oyster (Crassostrea gigas), was studied in a cell-based fluorometric antioxidant assay using human hepatocyte-derived cells (C3A) and diphenyl-1-pyrenylphosphine (DPPP) as a fluorescent probe. In comparison with two hydrophilic antioxidants, DHMBA showed the stronger inhibition of DPPP-mediated fluorescence than chlorogenic acid and l-ascorbic acid: at a concentration of 320 μM of DPPP, the inhibition was 26.4 ± 2.6%, 11.1 ± 1.2%, and 0 ± 2.0% for DHMBA, chlorogenic acid, and l-ascorbic acid, respectively (mean ± SD, n = 4). Their relative oxygen radical absorbance capacities (ORAC) were dissociated with their cell-based antioxidant activities: 1.47 ± 0.40, 4.57 ± 0.30, and 0.53 ± 0.13 μmol TE/μmol for DHMBA, chlorogenic acid, and l-ascorbic acid, respectively (mean ± SD, n = 4). The amphiphilicity of DHMBA was better than chlorogenic acid and l-ascorbic acid might underlie this dissociation. Since the C3A cells are human hepatoma-derived cells, DHMBA might be useful in the prevention and treatment of liver diseases by involving an oxidation process. 相似文献
12.
Alessandro Mantovani Paolo Gisondi Amedeo Lonardo Giovanni Targher 《International journal of molecular sciences》2016,17(2)
Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis. 相似文献
13.
Teresa Auguet Alba Berlanga Esther Guiu-Jurado Salomé Martinez José Antonio Porras Gemma Aragonès Fátima Sabench Mercé Hernandez Carmen Aguilar Joan Josep Sirvent Daniel Del Castillo Cristóbal Richart 《International journal of molecular sciences》2014,15(12):22173-22187
Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis. 相似文献
14.
Non-alcoholic fatty liver disease (NAFLD) is to date the most common chronic liver disease in clinical practice and, consequently, a major health problem worldwide. It affects approximately 30% of adults in the general population and up to 70% of patients with type 2 diabetes (T2DM). Despite the current knowledge of the epidemiology, pathogenesis, and natural history of NAFLD, no specific pharmacological therapies are until now approved for this disease and, consequently, general strategies have been proposed to manage it. They include: (a) lifestyle change in order to promote weight loss by diet and physical activity, (b) control of the main cardiometabolic risk factors, (c) correction of all modifiable risk factors leading the development and progression of advanced forms of NAFLD, and (d) prevention of hepatic and extra-hepatic complications. In the last decade, several potential agents have been widely investigated for the treatment of NAFLD and its advanced forms—shedding some light but casting a few shadows. They include some glucose-lowering drugs (such as pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors), antioxidants (such as vitamin E), statins or other lipid lowering agents, bile and non-bile acid farnesoid X activated receptor (FXR) agonists, and others. This narrative review discusses in detail the different available approaches with the potential to prevent and treat NAFLD and its advanced forms. 相似文献
15.
Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD. 相似文献
16.
Giuseppina Palladini Laura Giuseppina Di Pasqua Marta Cagna Anna Cleta Croce Stefano Perlini Barbara Mannucci Antonella Profumo Andrea Ferrigno Mariapia Vairetti 《International journal of molecular sciences》2022,23(12)
We evaluate the effects of the methionine-choline-deficient (MCD) diet on serum and hepatic zinc (Zn) and iron (Fe) and their relationships with matrix metalloproteinases (MMPs) and their modulators (TIMPs and RECK) as well as hepatic fatty acids using male Wistar rats fed 2-, 4- and 8-week MCD diets. Serum and hepatic Zn decrease after an 8-week MCD diet. Serum Fe increases after an 8-week MCD diet and the same occurs for hepatic Fe. An increase in hepatic MMP activity, associated with a decrease in RECK and TIMPs, is found in the MCD 8-week group. Liver Fe shows a positive correlation versus MMPs and RECK, and an inverse correlation versus TIMPs. A positive correlation is found comparing liver Zn with stearic, vaccenic and arachidonic acids, and an inverse correlation is found with linolenic and docosatetraenoic acids. An opposite trend is found between liver Fe versus these fatty acids. During NAFLD progression from steatosis to steatohepatitis, MCD rats exhibit an increase in Zn and a decrease in Fe levels both in serum and tissue associated with alterations in hepatic MMPs and their inhibitors, and fatty acids. The correlations detected between Zn and Fe versus extracellular matrix modulators and fatty acids support their potential role as therapeutic targets. 相似文献
17.
Utibe-Abasi S. Udoh Moumita Banerjee Pradeep K. Rajan Juan D. Sanabria Gary Smith Mathew Schade Jacqueline A. Sanabria Yuto Nakafuku Komal Sodhi Sandrine V. Pierre Joseph I. Shapiro Juan R. Sanabria 《International journal of molecular sciences》2022,23(13)
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, with an estimate of 0.84 million cases every year. In Western countries, because of the obesity epidemic, non-alcoholic steatohepatitis (NASH) has become the major cause of HCC. Intriguingly, the molecular mechanisms underlying tumorigenesis of HCC from NASH are largely unknown. We hypothesized that the growing uncoupled metabolism during NASH progression to HCC, manifested by lower cell redox status and an apoptotic ‘switch’ activity, follows a dysregulation of α1-Na/K-ATPase (NKA)/Src signalosome. Our results suggested that in NASH-related malignancy, α1-NKA signaling causes upregulation of the anti-apoptotic protein survivin and downregulation of the pro-apoptotic protein Smac/DIABLO via the activation of the PI3K → Akt pro-survival pathway with concomitant inhibition of the FoxO3 circuit, favoring cell division and primary liver carcinogenesis. Signalosome normalization using an inhibitory peptide resets apoptotic activity in malignant cells, with a significant decrease in tumor burden in vivo. Therefore, α1-NKA signalosome exercises in HCC the characteristic of a tumor suppressor, suggesting α1-NKA as a putative target for clinical therapy. 相似文献
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19.
Eman A. Ahmed Marwa O. El-Derany Ali Mostafa Anwar Essa M. Saied Sameh Magdeldin 《International journal of molecular sciences》2023,24(1)
With the rising incidence of hepatocellular carcinoma (HCC) from non-alcoholic steatohepatitis (NASH), identifying new metabolic readouts that function in metabolic pathway perpetuation is still a demand. The study aimed to compare the metabolic signature between NASH and NASH-HCC patients to explore novel reprogrammed metabolic pathways that might modulate cancer progression in NASH patients. NASH and NASH-HCC patients were recruited and screened for metabolomics, and isotope-labeled lipidomics were targeted and profiled using the EXION-LCTM system equipped with a Triple-TOFTM 5600+ system. Results demonstrated significantly (p ≤ 0.05) higher levels of triacylglycerol, AFP, AST, and cancer antigen 19-9 in NASH-HCC than in NASH patients, while prothrombin time, platelet count, and total leukocyte count were decreased significantly (p ≤ 0.05). Serum metabolic profiling showed a panel of twenty metabolites with 10% FDR and p ≤ 0.05 in both targeted and non-targeted analysis that could segregate NASH-HCC from NASH patients. Pathway analysis revealed that the metabolites are implicated in the down-regulation of necroptosis, amino acid metabolism, and regulation of lipid metabolism by PPAR-α, biogenic amine synthesis, fatty acid metabolism, and the mTOR signaling pathway. Cholesterol metabolism, DNA repair, methylation pathway, bile acid, and salts metabolism were significantly upregulated in NASH-HCC compared to the NASH group. Metabolite–protein interactions network analysis clarified a set of well-known protein encoding genes that play crucial roles in cancer, including PEMT, IL4I1, BAAT, TAT, CDKAL1, NNMT, PNP, NOS1, and AHCYL. Taken together, reliable metabolite fingerprints are presented and illustrated in a detailed map for the most predominant reprogrammed metabolic pathways that target HCC development from NASH. 相似文献
20.
Reda Albadawy Amany Helmy Hasanin Sara H. A. Agwa Shaimaa Hamady Yasmin M. Aboul-Ela Mona Hussien Raafat Samaa Samir Kamar Mohamed Othman Yahia A. Yahia Marwa Matboli 《International journal of molecular sciences》2022,23(17)
Background: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. Aim: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (HSPD1/TNF/MMP14/ITGB1) mRNAs and their upstream noncoding RNA regulators (miRNA-6881-5P and lnc-SPARCL1-1:2) in NASH rats. Results: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (HSPD1/TNF/MMP14/ITGB1) mRNAs and their epigenetic regulators (miRNA-6881-5P and lnc-SPARCL1-1:2). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-α, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. Conclusion: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (HSPD1, TNF, MMP14, and ITGB1) mRNAs—(miRNA-6881-5P—(lnc-SPARCL1-1:2) RNA panel. 相似文献