Previous reports on the association between retinol binding protein 4 (RBP4) and nonalcoholic fatty liver disease (NAFLD) were controversial. This study aimed to investigate the association between ...the serum RBP4 levels and occurrence of NAFLD in Chinese population. In total, 2938 participants aged 40-75 years were involved in this community-based cross-sectional study. General information, lifestyle factors, serum levels of RBP4 and the presence of NAFLD were determined. Patients with NAFLD had significantly higher concentrations of RBP4 (37.9 ± 6.8 μg/ml) than did non-NAFLD controls (35.0 ± 6.7 μg/ml) (P < 0.001). The odds ratios (ORs) of NAFLD for the highest (vs. lowest) quartile of RBP4 were 1.884 (95% CI: 1.391, 2.551) for females (P < 0.001), and 2.107 (95% CI: 1.357, 3.273) for male participants (P < 0.01) after adjusting for related factors. The serum RBP4 levels were positively associated with the prevalence of NAFLD in middle-aged and elderly Chinese people, and Homeostatic model assessment-insulin resistance (HOMA-IR), trunk fat, the waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) might be implicated in the pathogenesis of RBP4 in NAFLD.
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•Cy-3-g inhibited inflammation by regulating macrophage polarization.•Cy-3-g polarized LPS-induced M1 toward M2 macrophage.•Cy-3-g regulated M1-M2 polarization via PPARγ-mediated ...NF-κB and STAT6 signaling pathway.
Macrophage polarization exerts critical effect on inflammatory response. Cyanidin-3-O-β-glucoside (Cy-3-g), a typical anthocyanin pigment has been reported to have anti-inflammatory property. However, whether Cy-3-g exerts anti-inflammatory effects by modulating macrophage polarization remains unclear. Lipopolysaccharide (LPS) was used to establish the M1 model of J774 cells, in which the effects of Cy-3-g on M1-M2 conversion were explored. Cy-3-g (1, 10, 100 μM) not only reduced LPS-induced increased expression of proinflammatory factors and but also elevated the levels of anti-inflammatory factors. Moreover, Cy-3-g intervention shifted LPS-polarized M1 into M2, leading to the significant reduction of synthesis of nitric oxide synthase and major histocompatibility complex II (M1 markers), and increase of arginine I and CD206 expression (M2 markers). Further experiments found that Cy-3-g dose-dependently increased peroxisome proliferator-activated receptor-γ (PPARγ) expression. Finally, we determined that Cy-3-g regulated M1-M2 polarization via PPARγ-mediated nuclear factor κB and signal transducers and activators of transcription 6 signaling pathway.
Brussels chicory, a typical vegetable in Mediterranean diets, has been recently reported to stabilize advanced atherosclerotic plaques in the brachiocephalic artery of apoE-deficient (
) mice. ...Herein, we investigated whether Brussels chicory can stabilize advanced plaques in the aorta via improving oxidative stress. Thirty week old
mice were fed the AIN-93G diet or supplemented with 0.5% freeze-dried Brussels chicory for twenty weeks. Aortic plaque size and stability, aortic relaxation, monocyte adhesion to aortic endothelium, free radicals, and enzymatic and non-enzymatic factors involved in free radical production and elimination in aorta and serum were measured. Brussels chicory consumption did not alter aortic plaque size, however, it stabilized aortic plaques, promoted aortic relaxation, and also inhibited monocyte adhesion to aortic endothelium. Moreover, this administration reduced oxidized LDL (ox-LDL) and 4-hydroxynonenal (4-HNE) content in aortic plaques, associated with inhibited aortic NADPH oxidase (NOX) and uncoupled endothelial nitric oxide synthase (eNOS)-mediated free radical production. However, Brussels chicory consumption did not appreciably alter aortic and serum superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, aortic glutathione (GSH), as well as serum non-enzymatic antioxidants, such as bilirubin, uric acid, and GSH. Collectively, improved oxidative stress might contribute to the atheroprotective effect of Brussels chicory, supporting the prospect of the antioxidant therapy in advanced atherosclerosis progression.
Black rice and its pigment fraction may have antiatherogenic activity, but the exact component contributing to the beneficial effect remains unclear. The aim of the present study was to investigate ...the influence of the anthocyanin-rich extract from black rice on the vulnerability of advanced plaques in apolipoprotein (apo) E-deficient mice. Using LC-MS, the anthocyanin-rich extract from black rice was identified as containing cyanidin-3-glucoside and peonidin-3-glucoside. ApoE-deficient mice (n = 30; 30 wk old) were randomly divided into 3 groups: a control group (fed the AIN-93G diet), the simvastin group simva; fed the AIN-93G diet containing simvastatin, 50 mg/(kg·d), or the anthocyanin-rich extract group antho; fed the AIN-93G diet supplemented with anthocyanin-rich extract from black rice, 300 mg/(kg·d). After 20 wk of intervention, the plaque area that developed in the brachiocephalic artery of mice in the antho group was smaller than that of the control mice. Both the antho and simva groups had lower frequencies of the large necrotic core and thin fibrous cap in plaques than the control group. Collagen I was increased and matrix metalloproteinase-1 contents were reduced in the brachiocephalic lesion of both the antho and simva groups compared with the control group. Furthermore, mRNA levels of tissue factor and inducible nitric oxide synthase in aortae were decreased in the antho and simva groups. Supplementation of anthocyanin-rich extract improved the lipid profile by decreasing serum triglyceride, total cholesterol, and non-HDL cholesterol. These results suggest that chronic diet intake of anthocyanin-rich extract from black rice may enhance plaque stabilization in old apoE-deficient mice. The underlying mechanism is related mainly to inhibiting proinflammatory factors and improving the serum lipid profile.
Our previous studies have demonstrated that anthocyanin extract from black rice (AEBR) inhibits atherosclerosis. Whether dietary AEBR supplementation can affect platelet function, an important factor ...in the pathogenesis of cardiovascular diseases, remains unclear. The aim of the present study is to explore the effects and mechanisms of dietary AEBR supplementation on platelet function and lipid profile in dyslipidemic rats. We demonstrated herein that thromboxane A2, the thrombogenic ratio of thromboxane A2 and prostacyclin, serum calmodulin, and soluble P-selectin were significantly decreased in rats fed a high fat diet supplemented with AEBR. AEBR supplementation also remarkably lowered serum triglyceride and raised hepatic CPT-1 mRNA expression. These findings suggest that dietary intake of AEBR reduces platelet hyperactivity, hypertriglyceridemia, and body weight gain, and facilitates in the maintenance of optimal platelet function in dyslipidemic rats induced by high fat diets.
Background and aims Non-alcoholic fatty liver disease (NAFLD) has become a common chronic liver disease in the world. Simple steatosis (SS) is the early phase of NAFLD. However, the molecular ...mechanisms underlying the development of steatosis have not yet been fully elucidated. Methods Two public datasets (GSE48452 and GSE89632) through the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs) in the development of steatosis. A total of 72 participants including 38 normal histological controls and 34 SS patients were included in this study. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) network analysis were performed to explore the function of DEGs. The results were further confirmed in high-fat diet (HFD)-fed mice and oleate-treated HepG2 cells. Results Total 57 DEGs including 31 up- and 26 down-regulated genes between SS patients and healthy controls were determined. GO and KEGG analysis showed that most of the DEGs were enriched in the ligand–receptor signaling pathways. PPI network construction was used to identify the hub genes of the DEGs. MYC, ANXA2, GDF15, AGTR1, NAMPT, LEPR, IGFBP-2, IL1RN, MMP7, and APLNR were identified as hub genes, and IGFBP-2 expression was found to be reversely associated with hepatic steatosis, fasting insulin, HOMA-IR index, and ALT levels. In HFD-fed mice, hepatic IGFBP-2 was also downregulated and negatively associated with hepatic triglyceride (TG) levels. Moreover, overexpression of IGFBP-2 ameliorated the oleate induced accumulation of TGs in hepatocytes. Conclusions This study identified novel gene signatures in the hepatic steatosis and will provide new understanding and molecular clues of hepatic steatosis.
Vascular senescence, which is closely related to epigenetic regulation, is an early pathological condition in cardiovascular diseases including atherosclerosis. Inhibition of S-adenosylhomocysteine ...hydrolase (SAHH) and the consequent increase of S-adenosylhomocysteine (SAH), a potent inhibitor of DNA methyltransferase, has been associated with an elevated risk of cardiovascular diseases. This study aimed to investigate whether the inhibition of SAHH accelerates vascular senescence and the development of atherosclerosis.
The case-control study related to vascular aging showed that increased levels of plasma SAH were positively associated with the risk of vascular aging, with an odds ratio (OR) of 3.90 (95% CI, 1.17–13.02). Elevated pulse wave velocity, impaired endothelium-dependent relaxation response, and increased senescence-associated β-galactosidase staining were observed in the artery of SAHH+/- mice at 32 weeks of age. Additionally, elevated expression of p16, p21, and p53, fission morphology of mitochondria, and over-upregulated expression of Drp1 were observed in vascular endothelial cells with SAHH inhibition in vitro and in vivo. Further downregulation of Drp1 using siRNA or its specific inhibitor, mdivi-1, restored the abnormal mitochondrial morphology and rescued the phenotypes of vascular senescence. Furthermore, inhibition of SAHH in APOE−/− mice promoted vascular senescence and atherosclerosis progression, which was attenuated by mdivi-1 treatment. Mechanistically, hypomethylation over the promoter region of DRP1 and downregulation of DNMT1 were demonstrated with SAHH inhibition in HUVECs.
SAHH inhibition epigenetically upregulates Drp1 expression through repressing DNA methylation in endothelial cells, leading to vascular senescence and atherosclerosis. These results identify SAHH or SAH as a potential therapeutic target for vascular senescence and cardiovascular diseases.
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Background Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic ...dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. Objective To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. Method In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. Results Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 + or - 0.17 vs. 0.41 + or - 0.17, P = 0.015) and serum levels of gamma-glutamyl transpeptidase (GGT, -8.21 + or - 3.01 vs. 1.23 + or - 3.16, P = 0.042) and ApoB (-0.02 + or - 0.03 vs. 0.07 + or - 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. Conclusion These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. Trial registration The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043). Keywords: Metabolic dysfunction-associated steatotic liver disease, Silymarin, Liver stiffness, Gut microbiota, Randomized controlled study, Flavonoids, Phytochemicals
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, has been linked to insulin resistance and hepatic lipid metabolism and is suggested to be associated with nonalcoholic ...fatty liver disease (NAFLD). This study aimed to investigate the association of SHBG with NAFLD in Chinese adults.
We conducted a community-based, cross-sectional study in China involving 2912 participants aged 40-75 years old. All participants underwent detection for hepatic fat infiltration by ultrasound in addition to providing complete medical history and undergoing physical and blood biochemical examinations. The association of serum SHBG with the presence of NAFLD was reported by adjusted odds ratio after applying logistic regression models. To further explore the relationship between SHBG and NAFLD, mRNA expression of SHBG and hepatocyte nuclear factor 4-α (HNF4α), as well as intrahepatic triglycerides, were determined from the liver tissues of 32 subjects with different degrees of steatosis.
Serum SHBG levels in patients with NAFLD (median, 43.8 nmol/L; interquartile range, 33.4-56.8 nmol/L) were significantly lower than those in non-NAFLD subjects (median, 63.4 nmol/L; interquartile range, 47.6-83.1 nmol/L). Serum SHBG levels were inversely correlated with WHR, trunk fat percentage, glucose, HOMA-IR, TG, UA and DHEAS, and were positively correlated with HDL-C levels (all
< 0.001). Logistic regression analysis indicated that serum SHBG levels were negatively associated with the presence of NAFLD in all subjects, as well as the subgroups stratified by sex, BMI and HOMA-IR (all
< 0.05). In human liver tissues, SHBG and HNF4α mRNA expression decreased along with the elevated grade of hepatic steatosis. Both SHBG and HNF4α mRNA expression levels were negatively correlated with intrahepatic triglycerides.
These results demonstrate that SHBG levels were negatively associated with the presence of NAFLD in middle-aged and elderly Chinese adults.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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