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Hypercholesterolemia is a major risk factor for chronic metabolic diseases. Nevertheless, a whole-grain diet could ameliorate this issue in a number of ways, including by regulating bile acid metabolism. However, the potential mechanism is unclear. The aim of the current study is to explore the effects of whole-grain diets (brown rice diet and whole wheat diet) on bile acid homeostasis. After intervention for 8 weeks in mouse model, whole-grain diets showed reduced feed conversion ratio, and the lipid levels (total cholesterol (TC) and triglycerides (TG)) were also meliorated in the serum and liver of mice. Moreover, whole-grain diets reduced the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (cholesterol synthesis) in the liver of mice. Interestingly, whole-grain diets not only promoted the mRNA expressions of low-density lipoprotein receptor (LDLR), ATP binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) (reverse cholesterol transport) but also facilitated the expressions of cytochrome P450, family 7, subfamily a, polypeptide 1 (CYP7a1) and cytochrome P450, family 27, subfamily a, polypeptide 1 (CYP27a1) (bile acid synthesis). Further study found that whole-grain diets promoted intestinal bile acid reabsorption and reduced bile acid excretion. Our study provided a novel metabolic regulation of bile acids in response to reduced cholesterol levels induced by whole-grain diets.

Background The activation and recruitment of brown adipose tissue are promising and effective methods for treatment of obesity and related diseases due to its capacity to increase thermogenesis and improve energy metabolism. Several functional ingredients have demonstrated to activate brown adipocytes, leading to an increase in energy expenditure. Some of the functional ingredients extensively exist in grain, which is the primary resource of staple food in daily life around the world. Nowadays, wholegrains are recommended as more healthier foods than refined grains for the higher contents of functional ingredients, such as dietary fibre, polyphenols, and vitamins. Scope and approach In this review, we introduce the functional characteristics of thermogenic adipocytes according to recent knowledge and summarize the effects of functional ingredients of wholegrains on the activity of thermogenic adipocytes according to recent findings. Additionally, the recommendations for future research on these topics are proposed. Key findings and conclusions Many functional ingredients of wholegrains, including phenolic acids, cyanidin-3-glucoside, dietary fibers, zeaxanthin, lutein, phytanic acid, rutin, and octacosanol, positively affect the activity of brown adipocytes and browning of white adipocytes. These effects mainly lie in the development, differentiation, and thermogenesis of brown and white adipocytes. The precise molecular mechanisms are remains to be further studied, nevertheless the reasonable wholegrain diets are helpful for controlling obesity and energy metabolism. This article provides fundamental explanations for the regulation of wholegrains on obesity and novel potential for development of wholegrain functional foods.

l-Arabinose is a kind of plant-specific five-carbon aldose with benefits in type 2 diabetes mellitus. It has been shown to have good properties in improving glucose homeostasis, but the underlying molecular mechanisms are still not clear. Hepatic gluconeogenesis is critical for regulating glucose homeostasis. Here, this study aimed to investigate whether l-arabinose could improve glucose metabolism via suppressing hepatic gluconeogenesis. High-fat-high-sucrose diet (HFHSD) or high-sucrose diet (HSD)-fed mice were supplemented with or without l-arabinose for 12 weeks. Fasting blood glucose levels were measured and glucose tolerance test and the histological analysis were performed after l-arabinose administration. AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), peroxisome proliferator activated receptor-γ coactivator-1α (PGC1α), Forkhead box O1 (FoxO1), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression levels were determined by RT-PCR and western blotting. As expected, l-arabinose apparently decreased body weight and attenuated hyperglycemia and glucose intolerance caused by HFHSD or HSD. l-Arabinose also had beneficial effects on glycogen synthesis by inactivating GSK3β. The expression levels of gluconeogenic genes were all decreased by l-arabinose administration in vivo and in vitro. In addition, our work revealed that AMPK is required for the inhibitory effects of l-arabinose on hepatic gluconeogenesis. l-Arabinose significantly up-regulated the phosphorylated levels of AMPK and its downstream protein ACC. Furthermore, blocking AMPK signaling through an inhibitor (compound C) or siAMPK significantly attenuated the inhibition of hepatic gluconeogenesis and the promotion of glycogen synthesis with l-arabinose, indicating that the inhibitory effect of l-arabinose on hepatic gluconeogenesis was AMPK dependent. Our work revealed that l-arabinose is a promising natural product for the regulation of hyperglycemia through inhibition of hepatic gluconeogenesis by activating AMPK.

Objective: To investigate the changes of Notch-1 protein expression and the changes of Notch-1 and NICD contents in the sinoatrial node fat pad (SAN-FP) nerve plexus of canines with chronic atrial fibrillation in which atrial fibrillation of the left atrium was induced in chronic pacing canines, in order to elucidate the relationship between the Notch signaling pathway of the SAN-FP nerve plexus and the occurrence and development of atrial fibrillation. Methods: Healthy Beagle dogs weighing 18 ± 2.66 kg, aged 7 to 9 years were randomly divided into a sham operation (SO) group (n = 5) and an atrial fibrillation (AF) group (n = 5), respectively. Results: Atrial fibrillation was successfully induced in canines in the AF group by rapid pacing on the left atrium appendage. The scattered nerve plexus was observed in fat cells of the SAN-FP. In contrast with the SO group, Notch-1 protein expression in the AF group was significantly increased (P < 0.05). No significantly statistical differences were observed in the concentration of Notch-1 and NICD between the AF group and the SO group (P > 0.05). In addition, no statistical differences in baseline Notch-1 and NICD concentrations were observed between the AF group and the SO group (P > 0.05). After an 8-week study, the concentrations of Notch-1 and NICD in the AF group were significantly increased compared with the SO group (P < 0.05). Conclusion: During the occurrence and development of AF, Notch-1 was expressed in different phases in the SAN-FP nerve plexus. After combining with ligands, Notch-1 was activated as NICD to affect the downstream target genes.

Rationale: The molecular mechanisms underlying the pathogenesis of systemic insulin resistance in type 2 diabetes remain elusive. Growth hormone receptor (GHR) deficiency has long been known to improved insulin sensitivity. However, whether hepatic GHR overexpression or activation is a cause of insulin resistance is still unknown. The aim of this study was to identify the new role of GHR in systemic insulin resistance and explore the underlying mechanism. Method: Different samples obtained from obese humans, ob/ob mice, db/db mice, high-fat diet (HFD)-fed mice and primary mouse hepatocytes were used to evaluate the correlations between GHR and metabolic disorders. Recombinant adeno-associated viruses encoding GHR and STAT5 and GHR knockout mice were used to investigate the roles of hepatic GHR in glucose homeostasis. Tissue H&E, Oil Red O and PAS staining were performed for histomorphological analysis. Gel filtration chromatography was employed for the separation of serum RBP4-TTR complexes. Plasmids (related to GHR, STAT5 and HIF1α), siRNA oligos (siGHR and siSTAT5), luciferase activity and ChIP assays were used to explore the potential mechanism of hepatic GHR. Results: Here, we found that hepatic GHR expression was elevated during metabolic disorder. Accordingly, hepatic GHR overexpression disrupted systemic glucose homeostasis by promoting gluconeogenesis and disturbing insulin responsiveness in the liver. Meanwhile, hepatic GHR overexpression promoted lipolysis in white adipose tissue and repressed glucose utilization in skeletal muscle by promoting the circulating level of RBP4, which contributed to impaired systemic insulin action. A mechanistic study revealed that hepatic GHR disrupted systemic insulin sensitivity by increasing RBP4 transcription by activating STAT5. Additionally, overexpression of hepatic GHR promoted TTR transcriptional levels by enhancing the expression of HIF1α, which not only increased the protein stability of RBP4 but also inhibited renal clearance of RBP4 in serum. Conclusions: Hepatic GHR overexpression and activation accelerated systemic insulin resistance by increasing hepatic RBP4 production and maintaining circulating RBP4 homeostasis. Our current study provides novel insights into the pathogenesis of type 2 diabetes and its associated metabolic complications.

Gliadins are the main cause of wheat allergies, and the prevalence of gliadin allergy has increased in many countries. l-Arabinose, a kind of plant-specific five-carbon aldose, possesses beneficial effects on food allergy to gliadins. This study investigated the antiallergic activities and underlying mechanisms of l-arabinose in a wheat gliadin-sensitized mouse model. BALB/c mice were sensitized to gliadin by intraperitoneal injections with gliadin followed by being given a gliadin challenge. l-arabinose-treated mice exhibited a marked reduction in the productions of total immunoglobulin E (IgE), gliadin-specific IgE, gliadin-specific IgG1, and histamine, with an increase in IgG2a level as compared with gliadin-sensitized mice. Beside that, a significant decrease in Th2-related cytokine level, IL-4, and an increase in Th1-related cytokine level, IFN-γ, in the serum and splenocytes were observed after treatment with l-arabinose. l-Arabinose treatment also improved the imbalance of Th1/Th2 immune response on the basis of the expression levels of related cytokines and key transcription factors in the small intestine and spleen of sensitized mice. In addition, gliadin-induced intestinal barrier impairment was blocked by l-arabinose treatment via regulation of TJ proteins and suppression of p38 MAPK and p65 NF-κB inflammation signaling pathways. Notably, the results confirmed that l-arabinose treatment increased CD4+ Foxp3+ T cell populations and Treg-related factors associated with increased expression of IL-2 and activation of STAT5 in gliadin-sensitized mice. In conclusion, l-arabinose attenuated the gliadin-induced allergic symptoms via maintenance of Th1/Th2 immune balance and regulation of Treg cells in a gliadin-induced mouse model, suggesting l-arabinose could be used as a promising agent to alleviate gliadin allergy.

Bisphenol A (2,2-bis(4-hydroxyphenyl) propane, BPA) is a typical endocrine disruptor in aquatic environment. The removal of BPA by adsorption is a simple and effective way. Mesoporous carbon (MC) and N-modified mesoporous carbon (NMC) were synthesized by the soft template method and used for BPA adsorption. The adsorption performance of MC and NMC was investigated by the batch and dynamic system, and compared with commercial activated carbon (AC). Additionally, the kinetics and isotherms of BPA adsorption on MC and NMC were also investigated. The specific surface areas and average pore sizes of MC and NMC were 687.8 and 579.6 m2/g, 4.06 and 4 nm, respectively. The equilibrium adsorption capacity of MC and NMC was positively correlated with the initial BPA concentration, and negatively correlated with adsorbent dosages. The pH value of 3–8 was conducive to the adsorption of BPA on MC and NMC. Pseudo-second-order kinetic model and Freundlich isotherm model provided well fit for BPA adsorption on MC and NMC. Compared with AC, MC and NMC exhibited a higher adsorption capability and more stable recycling performance. In the dynamic adsorption tests, with the increase in BPA concentration and flow rate in the influent, the breakthrough time and saturation time are shortened. However, the increase in adsorption layer height extended the breakthrough time and saturation time.

Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks. HepG2 cells were incubated with repaglinide in the absence or presence of a KCNQ1 inhibitor or the pcDNA3.1-hKCNQ1 plasmid, after which the levels of Akt, IRS-2 and PI(3)K were determined. Our data showed that repaglinide significantly decreased HOMA-IR in patients with T2DM. Furthermore, the level of HOMA-IR was significantly reduced in those patients with CT or TT genotypes than CC homozygotes. The KCNQ1 inhibitor enhanced repaglinide efficacy on insulin resistance, with IRS-2/PI(3)K/Akt signaling being up-regulated markedly. As in our clinical experiment, these data strongly suggest that KCNQ1 genetic polymorphism influences repaglinide response due to the pivotal role of KCNQ1 in regulating insulin resistance through the IRS-2/PI(3)K/Akt signaling pathway. This study was registered in the Chinese Clinical Trial Register on May 14, 2013. (No. ChiCTR-CCC13003536).

Traditional and ethnic foods are characterized by their history. By this category, they are usually considered safe on the basis of experience within the jurisdiction where they are indigenous. Elsewhere they may face authorization requirements. Foods characterized by historical production methods may face challenges from modern food hygiene legislation. In some situations, exemptions apply that enable the continuation of traditional practices, despite food safety concerns. This chapter explores how food law addresses one or both of these issues in the United States, Australia and New Zealand, Brazil, China, and the European Union (EU). From the perspective of global harmonization, it is preferable for national systems to take account of experience elsewhere and to be flexible toward nonindustrial ways of production.

Background: Multiple organ dysfunction syndrome (MODS)-specific cellular electrophysiological changes have so far not been reported and it seemed unlikely that they were related to arrhythmogenesis. Methods and Results: Twelve dogs, weight 12 ± 2 kg, were divided into a control group (n = 6) and an MODS group (n = 6). MODS lasting for 72 h was induced by the ‘two-hit’ method in 6 dogs. Ventricular myocytes were enzymatically isolated. Early afterdepolarizations (EADs), action potential duration (APD) and L-type calcium currents (ICa,L) were assessed. Sinus arrhythmias in all MODS dogs (100%; 6 of 6) and premature ventricular beats in 4 MODS dogs (66%; 4 of 6) were recorded, while no arrhythmias were found in the control animals. The prolongation of the APD was associated with a decreased ICa,L, and frequently provoked EADs were the typical electrophysiological alterations in the myocytes of MODS dogs. The action potential prolongation was shortened, the ICa,L blocked and EAD suppressed by using verapamil (100 μmol/l) in the myocytes of MODS dogs (66%; 4 of 6). Conclusion: The changes in cellular electrophysiology within 72 h in the heart of MODS dogs are APD prolongation, markedly decreased ICa,L as well as frequently provoked EAD, the most common types of arrhythmia being sinus arrhythmia and premature ventricular beats. This study suggests that verapamil appears to be an effective agent in reversing alterations in cellular electrophysiology at the early stage of MODS.

Objective: The aim of this study was to explore the characteristics of digestive organ cancer mortality and the potential years of life lost in Inner Mongolia, and to provide evidence for the prevention of digestive organ cancers. Methods: Using data from the Death Registry System from 2009 to 2012, we classified male and female cancer deaths according to the International Classification of Disease (10th revision). The mortality and potential years of life lost were calculated for digestive organ cancers in Inner Mongolia. The average years of life lost was calculated. Results: Digestive organ cancer mortality in Inner Mongolia was higher in men than in women. The potential years of life lost were also much higher in men than in women. Gallbladder cancer, pancreatic cancer, and colorectal, anus, and anal canal cancer were the most prominent contributors to mortality. Esophageal cancer was the most prominent contributor to potential years of life lost, and was the leading cause of average years of life lost in both sexes. Conclusion: Liver cancer and stomach cancer mortality and the potential years of life lost to liver and stomach cancer are demonstrably higher in Inner Mongolia. Although esophageal cancer mortality was not the highest of the digestive organ cancers, the average years of life lost to esophageal was the highest for both sexes, and it should therefore be targeted for prevention.

OBJECTIVE: This study aimed to assess the characteristics of anemia-related deaths and the relationship between socio-demographic status and mortality risk of anemia in Inner Mongolia from 2008 to 2012.METHODS: We obtained our data for 2008–2012 from the Death Registry System of Inner Mongolia. We calculated the mortality, percentage, and potential years of life lost (PYLL) of anemia in diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism (DBDIM). We collected socio-demographic status of case and control, including marital status, education level, area of residence, and occupation. Logistic regression models were employed to analyze which factor has effect to mortality risk of anemia.RESULTS: The total mortality from anemia was 0.66/105, and the mortality rates in male and female were 0.74/105 and 0.57/105, respectively (χ2 = 1.270, P = 0.260). No significant differences in the mortality of anemia were observed from 2008 to 2012 (χ2 = 6.003, P = 0.199). In DBDIM approximately 80% of these deaths were caused by anemia. Among the various types of anemia, aplastic and other anemias (AOA) showed the highest PYLL and mortality. The age-specific mortality curve for anemia, which increased with age, is similar in both genders. Moreover, a high education level increased the mortality risk of anemia.CONCLUSION: Among the various types of anemia, AOA showed the highest PYLL and mortality, and the burden of premature death resulting from AOA is possibly more serious than other anemia. Moreover, high education level increased the mortality risk of anemia.

In this study, we aimed to determine the leukemia-related mortality rates and associated sociodemographic characteristics in the Inner Mongolia region of China. We obtained data for the period 2008–2012 from the Death Registry System maintained by the Inner Mongolia Centers for Disease Control and Prevention. We computed the percentages of leukemia-related deaths and controls diagnosed by various methods and at different levels of hospitals. The χ2 test was used to examine differences in leukemia-related mortality according to sex. We also calculated potential years of life lost (PYLL) and average years of life lost. Unconditional logistic regression models were used to analyze the effect of sociodemographic characteristics. The sex-adjusted leukemia-related mortality rate was 3.74/100 000. The mortality rate in men (4.27/100 000) was significantly higher than that in women (3.17/100 000), as was the respective PYLL (8040.5 vs. 6000.5 person-years). Mortality increased with increasing age in both men and women. The highest mortality rate was observed in those over 70 years of age for both men (18.36/100 000) and women (7.68/100 000). Men with a higher education level showed an increased risk of leukemia (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.02–2.07, P = 0.04). In men, unemployment was associated with leukemia-related death (OR = 0.63, 95% CI = 0.42–0.95, P = 0.03). The leukemia-related mortality rate in Inner Mongolia was higher than that worldwide and that in China. A higher level of education and unemployment were associated with leukemia-related mortality in Inner Mongolia.

A kind of RPC (Railway Static Power Conditioner) was discussed to govern power quality in V/V electric traction system of the high-speed railway at 350Km/h, which is used to carry out the comprehensive compensation of negative sequence, reactive power and harmonic currents in the traction substation. The paper analyzed the negative sequence compensation principle, and a dual-loop control strategy was proposed for RPC. A set of optimal PI parameters were obtained for inner-loop recursive PI controller with the method of third-order optimal design. A stable DC-link voltage is the prerequisite for normal operation of RPC, so a sub-PI control strategy was proposed to suppress DC-link voltage fluctuation, which is an accurate feedback control based on energy balance. Finally, the correctness of the analysis has been confirmed by the simulation and experiment results.

Objective To study electrical characteristics after engineering heart tissue (EHT)transplantation in myocardial infarction (MI) SD rat by a new technique of microelectrode arrays (MEA). Methods Thirty SD rats of both sexes weighing 220∼250g were sacrificed under chlorine hydrate 0.3 ml/100 mg anaesthesia and were randomly divided into three groups: control group (n=10), MI group (n=10) and transplantation group (n=10). The hearts were quickly removed Langendorff-perfused with Tyrode9s solution. We recorded field potential (FP) morphology, amplitude, activation-recovery interval (ARI) and activation-conduction duration at local myocardium with microelectrode arrays technique. Results The MEA clearly recorded FP morphology. FP amplitude is (485±21.21) mV and ARI is (235±7.07) ms in control group. Compared with infarction zone, border zone of MI and opposite zone of MI, FP amplitude and ARI were significantly lower in transplantation group (p Conclusion MEA is a sensitive, low noise, long-term, stable and local tissue action with a potential of multiple-channel recording and mapping system in small animal whole hearts. EHT transplantation can improve the function of MI rats.