Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice

The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3), a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO) mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD), or a WTD diet containing 10% flaxseed oil (WTD + FO) for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC), triacylglycerol catabolism (PPARα, CPT1A, and ACOX1), inflammation (NF-κB, IL-6, TNF-α, and MCP-1), and oxidative stress (ROS, MDA, GSH, and SOD)

Damage and failure mechanism of pre-static loaded rock under cyclic impact

To study the damage and failure mechanism of rocks under the coupling effect of high ground stress static load and cyclic impact disturbance generated by mining and excavation, the multi-strain rate dynamic static superposition rock mechanics test system was used to carry out the experiments with different pre-imposed static loads (0.45/0.65/0.85σc) superimposed cyclic impact and the same pre-imposed static load superimposed with cyclic impact loads of different frequencies (0.5/1.0/2.0 Hz). The experimental results indicate that the peak strength of rocks in the dynamic static superposition test is smaller than that in the static load test, and the maximum deformation is greater than that in the static load test, indicating that the dynamic static superposition load has a significant promoting effect on rock damage. The evolution of strength, deformation, and failure under dynamic and static superimposed loads are consistent, also, peak strength, fracture duration are linearly negatively correlated with pre-loading static, and logarithmically positively correlated with cyclic impact frequency. The maximum strain, fracture fractal dimension, and fragment fractal dimension are linearly positively correlated with pre-loading static, and logarithmically negatively correlated with cyclic impact frequency. Under different dynamic and static superpositions, the evolution trend of the fractal dimension of rock surface cracks and fragment sizes are basically consistent, and the former is larger than the latter, that shows the synchronicity of the development of rock surface and internal cracks, and rock surface cracks are more prone to generation and expansion. As the pre-loading static increases or the impact frequency decreases, the rock failure gradually intensifies, and the failure mode undergoes a transition from “inclined shear failure to vertical tensile failure to overall burst failure”. The burst failure position extends from bottom to overall. To quantify the damage mechanism of pre-loading static and cyclic impact, a dynamic static superimposed damage factor evolution model was established, which comprehensively considers static load damage, different peak, frequency, and number of cyclic impact damage, and strain rate strengthening effects. Further dynamic and static superposition experiments were conducted, and the error rates of rock peak strength obtained from theoretical calculations and experimental results were 0.5%, 1.8%, 0.6%, and 1.7%, respectively, the errors were relatively small. The theoretical calculation strength based on the superposition of dynamic and static damage factors is lower than the experimental strength. Preliminary analysis shows that this is due to the microscopic hysteresis of damage development under high-frequency cyclic impact. The actual cumulative damage generated by cyclic impact is less than single impact damage multiplied by cycle number. In the later stage, the microscopic testing can be carried out to explore the evolution law of rock microscopic damage under cyclic impact and further improve the theoretical model

No association of vitamin D binding protein gene polymorphisms with ulcerative colitis in Chinese patients

Abstract Object Vitamin D (VD) deficiency has been reported in patients with ulcerative colitis (UC), and polymorphism in the gene encoding the vitamin D binding protein (DBP) can affect the characteristics of DBP, thus affecting the level and function of VD in vivo . Previous studies have rarely reported on the potential relationship between DBP polymorphisms and UC. To investigate the associations between genetic variants in DBP genes and UC susceptibility in the Han Chinese population, in order to discern whether any differences exist between this population and those of other countries.Methods In this case-control study, the genotyping of DBP rs4588 and rs7041 polymorphisms was conducted using polymerase chain reaction (PCR)-ligase detection reactions, and the rs4588 and rs7041 genotypes were detected by PCR-restriction fragment length polymorphism.Results In our case-control cohort, no significant difference was observed in the UC risk for either of the two SNPs (rs4588 and rs7401) in the DBP genes ( P &gt; 0.05). No association between UC susceptibility and the DBP gene haplotypes was found either.Conclusions Our results suggest that the two SNPs (rs4588 and rs7401) in the DBP genes may have no correlation with susceptibility to UC in the Chinese Han population. But interestingly, haplotype GC, which contains the rs4588 and rs7041 variants in the DBP gene, may affect the level of oxidative stress in UC patients, especially the level of MDA.</jats:p

The Effect of Iron Dextran on Vitamin D3 Metabolism in SD Rats

Abstract Background: The status of iron and vitamin D (VD) is essential to health. Previous studies have shown that iron homeostasis has a potential effect on VD metabolism, but the mechanism is not fully understood. Objectives: To explore the relationship between VD metabolism and iron metabolism, as well as the regulatory mechanism of iron on VD metabolism. Methods: Methods: 40 male rats were fed adaptively for 7 days and randomly divided into control (C, n=6 normal diet) group and model (M, n=24 iron deficient diet) group according to body weight, the latter was used to establish iron deficiency anemia (IDA) model. After 6 weeks of feeding, the M group was randomly divided into: deficiency iron group (DFe), low iron group (LFe), medium iron group (MFe) and high iron group (HFe) according to the level of hemoglobin (Hb). Different doses of iron dextran (based on iron content (100g·bw·d)): 0, 1.1, 3.3 and 9.9mg were given respectively. After 4 weeks, the rats were anesthetized with 8% chloral hydrate, blood was collected from the abdominal aorta, liver and kidney tissues were collected. The serum and tissues were separately packed and frozen at -80℃ for testing. Results: The results showed that the levels of Hb, RBC, serum iron (SI), liver iron, and kidney iron DFe group were lower than those in the other four groups, while the levels of total iron-binding capacity (TIBC), transferrin (TF) and transferrin receptor (Tfr) in DFe group were higher than those in other groups; The serum levels of 25-(OH)D3 and 1,25-(OH)2D3 in DFe group were significantly lower than those in C group (P &lt; 0.05). The correlation analysis showed that the levels of 25-(OH)D3 and 1,25-(OH)2D3 were negatively correlated with TIBC, TF and Tfr no correlation with SI. Western blot, immunofluorescence, and q-PCR results showed that compared with C group, the protein and gene expressions of CYP2R1, CYP27A1, and CYP24A1 in DFe group were down-regulated, and the expression of CYP27B1 protein and gene was up-regulated in DFe group. Conclusion: Therefore, iron may be involved in the metabolism of VD3 by regulating the expression of VD3 hydroxylase, suggesting that appropriate iron supplementation can promote the activation of VD3.</jats:p

VDR Pathway-Specific Dose-Related Effects of 1,25(OH)2D3 on Salmonella typhimurium-induced Mouse Colitis

Abstract Background: Whether and how 1,25(OH)2D3 supplementation influences VDRs in experimental mice with colitis remains to be seen. To explore the effect of 1,25(OH)2D3 on S. typhimurium colitis through the VDR pathway and to discover the role of VDR in its action. Methods: We established a mouse UC model induced by S. typhimurium. After streptococcal typhus infection, the mice were fasted for 12 hours. Blood was collected by the eyeball extraction method, and then sacrificed by cervical dislocation, specimens were collected for corresponding indicators. Results: Mice exposed to S. typhimurium infection developed signs of acute colitis. After HE staining were performed on the diseased colons from the mice. high dose VD supplementation, the pathological colonic damage did not improve in the mice, and there was no statistical difference between the groups with VD deficiency (P&gt;0.05). VDR expression in the UC group treated with Salmonella was higher than that in the control group, a statistically significant difference (P&lt;0.01). Compared with the VDD+UC group, VDR expression rose in both the LVDS+UC group and the HVDS+UC group, with VDR protein expression being highest after high dose VD supplementation (P&lt;0.01). Compared with the control and the UC groups, the VDR mRNA expression level in the VDD+UC group was significantly higher, and the colon VDR mRNA expression level decreased after active VD supplementation (Fig.7C). Conclusions: Our data suggest the need for defining the accurate 1,25(OH)2D3 dose limits that induce an anti-inflammatory effect as current data indicate that higher doses would produce an inflammatory response.</jats:p

The effect of iron dextran on vitamin D3 metabolism in SD rats

Abstract Background Iron and vitamin D (VD) is essential to health. Previous studies have shown that iron homeostasis has a potential effect on VD metabolism, but the mechanism is not fully understood. Objectives To explore the relationship between VD metabolism and iron metabolism, as well as the regulatory mechanism of iron on VD metabolism. Methods 40 male rats were fed adaptively for 7 days and randomly divided into control (C, n = 6 normal diet) group and model (M, n = 24 iron deficient diet) by simple randomization, the latter was used to establish iron deficiency anemia (IDA) model. After 6 weeks of feeding, the M group was randomly divided into: iron deficiency group (DFe), low iron group (LFe), medium iron group (MFe) and high iron group (HFe) by block randomization. Different doses of iron dextran (based on iron content (100 g·bw·d)): 0, 1.1, 3.3 and 9.9 mg) were given respectively. After 4 weeks, the rats were anesthetized with 8% chloral hydrate, Blood (collected from the abdominal aorta), liver and kidney tissues were collected. The serum and tissues were separately packed and frozen at -80℃ for testing. Results The results showed that the levels of hemoglobin (Hb), red blood cell (RBC), serum iron (SI), liver iron, and kidney iron in DFe group were lower than those in the other four groups, while the levels of total iron-binding capacity (TIBC), transferrin (TF) and transferrin receptor (Tfr) in DFe group were higher than those in other groups; The serum levels of 25-(OH)D3 and 1,25-(OH)2D3 in DFe group were significantly lower than those in C group (P < 0.05). The correlation analysis showed that the levels of 25-(OH)D3 and 1,25-(OH)2D3 were negatively correlated with TIBC, TF and Tfr no correlation with SI. Western blotting, immunofluorescence, and q-PCR results showed that compared with C group, the protein and gene expressions of CYP2R1, CYP27A1, and CYP24A1 in DFe group were down-regulated, and the expression of CYP27B1 protein and gene was up-regulated in DFe group. Conclusion Iron may be involved in the metabolism of VD3 by regulating the expression of VD3 hydroxylase, suggesting that appropriate iron supplementation might promote the activation of VD3

Combined effect of vitamin C and vitamin D3 on intestinal epithelial barrier by regulating Notch signaling pathway

Abstract Background Tight junction proteins play crucial roles in maintaining the intestinal mucosal barrier. Although previous studies have shown that Notch signaling is closely related to tight junction proteins, the mechanism remains unclear. This study was performed to investigate whether vitamin C combined with vitamin D3 affects intestinal mucosal barrier stability via the Notch signaling pathway. Methods Intestinal epithelial barrier and notch signaling pathway were studied using guinea pig and SW480 cells. The guinea pigs were randomized into four groups (n = 6 in each group): control group (C, 200 IU/kg d VD3 + 100 mg/kg d VC), low VC group (LVC, 200 IU/kg d VD3 + 10 mg/kg d VC), medium VC group (MVC, 200 IU/kg d VD3 + 100 mg/kg d VC), and high VC group (HVC, 200 IU/kg d VD3 + 200 mg/kg d VC). Except for the control group, the other three groups were freely drinked with 2% dextran sodium sulfate solution for 4 days. And the control group was free to drink distilled water. The following cell groups were used: control group (SW480 cells without intervention); LPS group (100 ng/mL LPS); VD3 group (0.1 μmol/L VD3); VC + VD3 group (0.1, 1, 5, 10 μmol/mL VC + 0.1 μmol/L VD3). Results Electron microscopy analysis revealed that both low and high doses of vitamin C combined with vitamin D3 maintained dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal epithelium tight junction. Compared with the control group, the expression level of ZO-1 mRNA in the colon tissue of the high-dose vitamin C group was significantly increased. In SW480 cell experiments, compared with the control group, cell migration and repair following treatment with different concentrations of vitamin C combined with vitamin D3 were significantly improved and the protein expression of Notch-1 was increased, whereas the protein expression of claudin-2 was significantly decreased. Thus, our results demonstrate that an appropriate amount of vitamin C combined with vitamin D3 can regulate the expression of claudin-2 by regulating Notch-1, relieve destruction of the intestinal mucosal barrier, and promote the repair of damage to the cell mucosal barrier. Conclusions We found that vitamin C combined with vitamin D3 protected against dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal mucosa. </jats:sec

Lycopene alleviates age-related cognitive deficit via activating liver-brain fibroblast growth factor-21 signalling

Brain function is linked with many peripheral tissues, including the liver, where hepatic fibroblast growth factor 21 (FGF21) mediates communication between the liver and brain. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, we investigated the effects of LYC on age-related memory impairment and the relative contribution of liver-brain FGF21 signaling in these process. The results showed that after treatment with LYC for 3 months, brain aging and age-related cognitive deficits were effectively managed. In addition, LYC ameliorated neuronal degeneration, mitochondrial dysfunction and synaptic damage, and promoted synaptic vesicle fusion in 18-month-old mice. Notably, LYC activated liver-brain FGF21 signalling in aging mice. Whereas all these central effects of LYC were negated by blocking FGF21 via i. v. injection of adeno-associated virus in aging mice. Furthermore, recombinant FGF21 elevated mitochondrial ATP levels and enhanced synaptic vesicle fusion in mouse hippocampal HT-22 cells, which promoted neurotransmitter release. Additionally, we co-cultured hepatocytes and neurons in Transwell and found that LYC enhanced hepatocytes’ support for neurons. This support included improved cell senescence, enhanced mitochondrial function, and increased axon length in co-cultured neurons. In conclusion, LYC protects against age-related cognitive deficit, partly explained by activating liver-brain FGF21 signalling, hence promoting neurotransmitters release via increasing mitochondrial ATP levels and enhancing synaptic vesicle fusion. These findings revealed that FGF21 could be a potential therapeutical target in nutritional intervention strategies to improve cognitive damage caused by aging and age-related neurodegenerative diseases

The Combined Effect of Vitamin C and Vitamin D3 on the Intestinal Epithelial Barrier by Regulating Notch Signaling Pathway

Abstract Background: Tight junction proteins play crucial role in maintaining the intestinal mucosal barrier. Although previous studies had shown that the Notch signal is closely related to tight junction proteins, the mechanism by which it does so remains unknown. The goal of the present study was to investigate whether vitamin C combined with vitamin D3 affects intestinal mucosal barrier stability through Notch signal pathway.Results: To assess the effect of vitamin C combined with vitamin D3 on the intestinal mucosal barrier, electron microscopic observation of ultrastructure of tight junctions was done. And tight junction proteins gene and Notch signal gene expression were analyzed by quantitative reverse-transcription polymerase chain reaction, expression of tight junction protein in SW480 cells interfered with by LPS were examined by western blot. We found that vitamin C combined with vitamin D3 had protective effect on DSS-induced ulcerative colitis in guinea pig intestinal mucosa. Electron microscopy results showed that both low dose and high dose of vitamin C combined with vitamin D3 could maintain DSS-induced ulcerative colitis in guinea pig intestinal epithelium tight junction, however, the combination of medium dose vitamin C and vitamin D3 did not have this effect; Compared with the control group, the expression level of ZO-1 mRNA in the colon tissue of high-dose vitamin C group was significantly increased. In SW480 cell experiments, compared with the control group, the cell migration and repair ability of different concentrations of vitamin C combined with vitamin D3 group were significantly improved, the protein expression of Notch-1 was increased, but the protein expression of claudin-2 was significantly decreased. Conclusions: our results of this experiment showed that the appropriate amount of vitamin C combined with vitamin D3 might regulate the expression of claudin-2 by regulating Notch-1, slow the intestinal mucosal barrier destruction, and promote the damage repair of cell mucosal barrier.</jats:p