Analysis of trans-resveratrol and trans-piceid in vegetable foods using high-performance liquid chromatography.

Trans-resveratrol and resveratrol glucoside are natural phenolic compounds existed in a wide variety of plant species, which are extensively consumed in many countries. The existing studies excessively focused on grapes and their products, and little about daily vegetable foods. Actually, in much more countries, vegetable foods are residents' principal food and nutrient origins. This study was to investigate the levels of trans-resveratrol and trans-piceid in daily vegetable foods of China using high-performance liquid chromatography (HPLC) method with fluorescence detection (FLD). Trans-piceid was the major form existing in most vegetable foods, and most of the samples contained higher trans-piceid than trans-resveratrol. The contents of trans-resveratrol and trans-piceid in different varieties and regions were different. Moreover, peculiar vegetable foods to some region were also one of the most important sources of trans-resveratrol and trans-piceid. Therefore, vegetable foods were other significant sources of trans-resveratrol and trans-piceid except the foods published.

Curcumin protects against rotenone-induced Parkinson's disease in mice by inhibiting microglial NLRP3 inflammasome activation and alleviating mitochondrial dysfunction.

Parkinson's disease (PD) is a common neurodegenerative disorder worldwide. Currently, treatment options can only relieve symptoms but cannot prevent, slow, or halt the neurodegenerative process of PD. Much evidence has suggested that microglia-mediated neuroinflammation is involved in the pathophysiology of PD. As an anti-inflammatory agent, curcumin may exert a neuroprotective effect on PD. However, its mechanism has yet to be demonstrated clearly. Our results indicated that curcumin alleviated rotenone-induced behavioral defects, dopamine neuron loss, and microglial activation. Besides, the NF-κB signaling pathway, the NLRP3 inflammasome, and pro-inflammatory cytokines, including IL-18 and IL-1ß, contributed to the microglia-mediated neuroinflammation in PD. Furthermore, Drp1-mediated mitochondrial fission causing mitochondrial dysfunction also had an etiological role in the process. This study suggests that curcumin protects against rotenone-induced PD by inhibiting microglial NLRP3 inflammasome activation and alleviating mitochondrial dysfunction in mice. Thus, curcumin may be a neuroprotective drug with promising prospects in PD.

Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT1 receptor antagonists.

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity.

The Potential Roles of Exosomal Non-Coding RNAs in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth highest-incidence cancer and the 4th most deadly cancer all over the world, with a high fatality and low diagnostic rate. Nowadays, Excessive alcohol consumption, type-2 diabetes, smoking and obesity have become some primary risk factors of HCC. As intercellular messenger transporting information cargoes between cells, exosomes are a type of extracellular vesicles (EVs) released by most types of cells including tumor cells and non-tumor cells and play a pivotal role in establishing an HCC microenvironment. Exosomes, and more generally EVs, contain different molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids and transcription factors. The three main ncRNAs in exosomes are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs). NcRNAs, identified as essential components, are selectively sorted into exosomes and exosomal ncRNAs show great potential in regulating tumor development, including proliferation, invasion, angiogenesis, metastasis, immune escape and drug resistance. Here, we chiefly review the formation and uptake of exosomes, classification of exosomal ncRNAs and current research on the roles of exosomal ncRNAs in HCC progression. We also explored their clinical applications as new diagnostic biomarkers and therapeutic avenues in HCC.

Predominant contribution of syntrophic acetate oxidation to thermophilic methane formation at high acetate concentrations.

To quantify the contribution of syntrophic acetate oxidation to thermophilic anaerobic methanogenesis under the stressed condition induced by acidification, the methanogenic conversion process of 100 mmol/L acetate was monitored simultaneously by using isotopic tracing and selective inhibition techniques, supplemented with the analysis of unculturable microorganisms. Both quantitative methods demonstrated that, in the presence of aceticlastic and hydrogenotrophic methanogens, a large percentage of methane (up to 89%) was initially derived from CO(2) reduction, indicating the predominant contribution of the syntrophic acetate oxidation pathway to acetate degradation at high acid concentrations. A temporal decrease of the fraction of hydrogenotrophic methanogenesis from more than 60% to less than 40% reflected the gradual prevalence of the aceticlastic methanogenesis pathway along with the reduction of acetate. This apparent discrimination of acetate methanization pathways highlighted the importance of the syntrophic acetate-oxidizing bacteria to initialize methanogenesis from high organic loadings.

The Role of RNA Methyltransferase METTL3 in Hepatocellular Carcinoma: Results and Perspectives.

Hepatocellular carcinoma (HCC) is the 6th most prevalent cancer and the 4th leading cause of cancer-related death worldwide. Mechanisms explaining the carcinogenesis of HCC are not clear yet. In recent years, rapid development of N6-methyladenosine (m6A) modification provides a fresh approach to disclosing this mystery. As the most prevalent mRNA modification in eukaryotes, m6A modification is capable to post-transcriptionally affect RNA splicing, stability, and translation, thus participating in a variety of biological and pathological processes including cell proliferation, apoptosis, tumor invasion and metastasis. METTL3 has been recognized as a pivotal methyltransferase and essential to the performance of m6A modification. METTL3 can regulate RNA expression in a m6A-dependent manner and contribute to the carcinogenesis, tumor progression, and drug resistance of HCC. In the present review, we are going to make a clear summary of the known roles of METTL3 in HCC, and explicitly narrate the potential mechanisms for these roles.

Dose and time-dependent hypercholesterolemic effects of iodine excess via TRbeta1-mediated down regulation of hepatic LDLr gene expression.

BACKGROUND: With the global improvement of iodine nutrition, iodine excess is emerging as a new concern. AIM OF STUDY: The aim of this study is to illustrate the physiological effects and potential molecular mechanisms of excessive iodine intake on lipid metabolism. METHODS: Balb/c mice were given drinking water containing different levels of iodine for 1 month and treated with 1.2 microg/mL iodine for different periods of time, respectively. Plasma lipid parameters and serum thyroid hormones were measured. Expressions of hepatic genes were detected by real-time polymerase chain reactions and Western blot. RESULTS: Dose-dependent hypercholesterolemic effects were detected in mice (TC, r = 0.615; p < 0.01). Drinking 1.2 microg/mL iodine water for 1 month had no significant effect on serum lipid metabolism, while prolonged exposure induced an increase of serum cholesterol. Serum thyroid hormones were not affected by iodine throughout the study. At the molecular level, we detected a dose-dependent attenuation of hepatic low density lipoprotein receptor (LDLr) and thyroid hormone receptor beta1 (TRbeta1) expression in parallel to the change of serum cholesterol. Treatment with 1.2 microg/mL iodine water for 1 month did not affect LDLr and TRbeta1 expression, while 3 or 6 months exposure resulted in a decrease of their expression. CONCLUSION: Present findings demonstrated dose- and time-dependent hypercholesterolemic effects of iodine excess. Furthermore, our data suggests that TRbeta1-mediated down regulation of hepatic LDLr gene may play a critical role in iodine excess-induced hypercholesterolemic effects.

The diabetogenic effects of excessive ethanol: reducing beta-cell mass, decreasing phosphatidylinositol 3-kinase activity and GLUT-4 expression in rats.

The diabetogenic impact of ethanol remains as a focal point of basic and clinical investigations. In this study, Wistar rats were subjected to daily intragastric ethanol administration (10 ml/kg body weight injection with 0 (control), 10, 20 and 33 % (v/v) ethanol in the injections, respectively) for 19 weeks. At the end of the administration, we found that the fasting plasma glucose level of the 33 % (v/v) ethanol-loaded group was 18 % higher than the control. Insulin sensitivity was decreased in a dose-dependent manner in all the ethanol-loaded groups (r - 0.842, P < 0.001) during intraperitoneal insulin tolerance test. Necrotic/haemorrhagic injury was detected in the pancreas and islet beta-cell mass was significantly reduced in the 33 % (v/v) ethanol-loaded rats by immunohistochemical and morphometric analysis. At the molecular level, we detected a dose-dependent attenuation of phosphatidylinositol 3-kinase activity (r - 0.956, P < 0.001) and GLUT-4 expression (GLUT-4 mRNA, r - 0.899, P < 0.001; GLUT-4 protein, r - 0.964, P < 0.001) in skeletal muscle. These results demonstrated that drinking is a conditional aetiological factor for diabetes and excessive ethanol intake is negatively associated with both insulin sensitivity and beta-cell mass. The whole-body insulin resistance might result from the ethanol-induced insulin signalling defects in muscle.

Regulating the hydrolysis of organic wastes by micro-aeration and effluent recirculation.

In this study, the effects of micro-aeration and liquid recirculation on the hydrolysis of vegetable and flower wastes during two-phase solid-liquid anaerobic digestion were assessed. To accomplish this, we evaluated the hydrolysis of five batches of waste that were treated under the following conditions: anaerobic, insufficient micro-aeration (aeration for 5 min every 24 h), and sufficient micro-aeration (aeration for 5 min every 12, 4 and 1h). Hydrolysis was found to depend on the level of micro-aeration. Specifically, insufficient micro-aeration led to unstable and decreased performance. Conversely, sufficient micro-aeration promoted the hydrolysis of easily biodegradable carbohydrates and proteins, but the microbial activity was later impaired by liquid recirculation using methanogenic effluent. The hydrolysis efficiency under anaerobic conditions was comparable to the efficiency observed under sufficient micro-aeration, while the cumulative TOC of the anaerobic batch was 1.4-2.4 times higher than that of the micro-aerated batches. In addition, liquid recirculation did not have a negative effect on the development of microbial activity under anaerobic conditions, which resulted in the lignocelluloses having a higher hydrolysis efficiency.

Nutritional status of under-five children from urban low-income families in Xiangtan and Jilin in China.

There have been many studies on the nutrition and the growth status of children from rural and remote western regions of China, whereas researches on children from urban low-income families are scarce. This study aimed to investigate the growth and nutritional status of children under five years of age from urban low-income families in China. There were 169 children aged 25-60 months recruited from Xiangtan and Jilin, two cities with a population of 2.81 million and 4.26 million respectively, in China in this cluster cross-sectional study. Data were collected on demographic and socioeconomic characteristics, the feeding practices and the incidence of anemia and diarrhea. The results showed that the prevalence of low birth weight and macrosomia was 7.1% and 9.5% for the two cities, respectively, which was higher than that for other cities in China (1.5% and 5.9%). Of all the sampled children, 14.6% and 8.2% suffered anemia and diarrhea, respectively. Multivariate analysis showed that legumes or nuts fed in a 24-h recall increased the risk of anemia (OR=4.9). Children whose caregivers began to introduce complementary foods relatively late would have high diarrhea prevalence (OR=1.4). In conclusion, the prevalence of anemia and diarrhea in under-five children from urban low-income families in China is relatively high. The growth and nutritional status of these children is greatly affected by feeding practices. A series of measures should be taken by relevant government departments to improve the health of these children.

[Influence of chronic ethanol intake insulin sensitivity and IR, IRS-1, IRS-2 mRNA expression of liver in male rats].

OBJECTIVE: To investigate the effect of ethanol intake on the insulin sensitivity of hepatic tissue in male rats and explores its possible molecular mechanisms. METHODS: Wister rats were administrated ethanol at a dose of 0 (control), 0.8 (low ethanol, L), 1.6 (medium ethanol, M) and 2.4 g/kg (high ethanol, H) daily, respectively. Each group had ten males. Nineteen weeks later, serum was collected for testing of fasting plasma glucose and insulin. Total liver RNA was extracted. The expression levels of IR, IRS-1, IRS-2 mRNA in hepatic tissue were detected by RT-PCR. RESULTS: Compared with the control group, the glucose concentration significantly increased in H ethanol groups (P < 0.05), the insulin concentration significantly increased in L and M ethanol groups (P < 0.05), HOMA-IR significantly increased in every ethanol group (P < 0.05). IR mRNA expression remarkably decreased in every ethanol group. IRS-1, IRS-2 mRNA expression increased in L and M ethanol groups but decreased in H ethanol group. CONCLUSION: The present study showed that ethanol abuse could induce to insulin resistance. The decreased of IR, IRS-1, IRS-2 mRNA expression of liver may be involved in the molecular mechanism of the effects of ethanol on insulin insensitivity.

[Oxidative damage and apoptosis in NIT-1 cells induced by ethanol].

OBJECTIVE: To decide whether ethanol induce apoptosis in mouse insulinoma cells (NIT-1) and the potential mechanism involved. METHODS: After NIT-1 cells were exposed to various concentrations of ethanol, agarose gel electrophoresis was used to detected DNA fragmentation. malondialdehyde (MDA) content, glutathione (GSH) level, superoxide dismutase(SOD) and glutathione peroxidase (GSH-Px) were measured in NIT-1 cells to evaluate the oxidative damage degree. Caspase-3 relative activity was determined by colorimetric assay. RESULTS: The results showed a "DNA ladder" pattern after treated with ethanol in NIT-1 cells. The MDA content was higher, the SOD activity, GSH-Px activity and GSH content were lower in ethanol group than those of control group. Ethanol increased the caspase-3 activity by a dose and time dependent manner. CONCLUSION: Higher concentration of ethanol induces imbalance of oxidation and antioxidative ability in NIT-1 cells, and oxidative stress further leads to apoptosis which may be related to the increased caspase-3 activity.

Discovery of novel, potent and low-toxicity angiotensin II receptor type 1 (AT1) blockers: Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazoles with a chiral center.

Novel angiotensin II receptor type 1 (AT1) blockers bearing 6-substituted carbamoyl benzimidazoles with a chiral center were designed and synthesized as the first step to develop new antihypertensive agents and understand their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [(125)I] Sar(1) Ile(8)-Ang II, which was specifically bound to human AT1 receptor. Radioligand binding assays revealed nanomolar affinity in several compounds under study. The IC50 values of nine ligands were higher than those of Losartan. The screening of decreased blood pressure in spontaneous hypertensive rats displayed that compound 8S (IC50 = 5.0 nM) was equipotent with Losartan, whereas compounds 13R (IC50 = 7.3 nM), 14R (IC50 = 6.3 nM), and 14S (IC50 = 3.5 nM) were slightly ahead of Losartan, and the most significant activity was demonstrated by compound 8R (IC50 = 1.1 nM). Candidate 8R was identified for its excellent efficacy in antihypertension and fairly low toxicity based on plasma analyses, toxicology studies, and chronic oral tests. Finally, compound 8R exhibited strong and multiple interactions with target active sites of the theoretical AT1 receptor model in docking study.

Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats.

AIM: To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease (NAFLD) and the related underlying mechanism. METHODS: After 9 d of acclimation to a constant temperature-controlled room (20 °C-22 °C) under 12 h light/dark cycles, male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet (n = 8) or a high-fat diet (HFD) (n = 32) for 10 d. Animals receiving HFD were then randomly divided into 4 groups and administered with 0, 12.5, 25, or 50 mg/kg (body weight) per day of lutein for the next 45 d. At the end of the experiment, the perinephric and abdominal adipose tissues of the rats were isolated and weighed. Additionally, serum and liver lipid metabolic condition parameters were measured, and liver function and insulin resistance state indexes were assessed. Liver samples were collected and stained with hematoxylin eosin and Oil Red O, and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses. RESULTS: Our data showed that after being fed a high-fat diet for 10 d, the rats showed a significant gain in body weight, energy efficiency, and serum total cholesterol (TC) and triglyceride (TG) levels. Lutein supplementation induced fat loss in rats fed a high-fat diet, without influencing body weight or energy efficiency, and decreased serum TC and hepatic TC and TG levels. Moreover, lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content, and also improved insulin sensitivity. Lutein administration also increased the expression of key factors in hepatic insulin signaling, such as insulin receptor substrate-2, phosphatidylinositol 3-kinase, and glucose transporter-2 at the gene and protein levels. Furthermore, high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1, which are associated with lipid metabolism and insulin signaling. CONCLUSION: These results demonstrate that lutein has positive effects on NAFLD via the modulation of hepatic lipid accumulation and insulin resistance.

Resveratrol ameliorates high glucose and high-fat/sucrose diet-induced vascular hyperpermeability involving Cav-1/eNOS regulation.

Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (ß-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation.

Iodine excess induces hepatic steatosis through disturbance of thyroid hormone metabolism involving oxidative stress in BALB/c mice.

Iodine excess is emerging as a new focus. A better understanding of its hazardous effects on the liver will be of great benefit to health. The aim of this study is to illustrate the effects of iodine excess on hepatic lipid homeostasis and explore its possible mechanisms. One hundred twenty BaLB/c mice were given iodine at different levels (0, 0.3, 0.6, 1.2, 2.4, and 4.8 mg I/L) in drinking water for 1 or 3 months. Lipid parameters and serum thyroid hormones were measured. Hepatic type 1 deiodinase activity and oxidative stress parameters were evaluated. The mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) was detected by real-time polymerase chain reaction. Dose-dependent increase of hepatic triglyceride content was detected (r = 0.680, P < 0.01) in iodine-loaded groups. Evident hepatic steatosis was observed in 2.4 and 4.8 mg I/L iodine-loaded groups. The activities of antioxidant enzymes (glutathione peroxidase and superoxide dismutase) were decreased, and the malondialdehyde level was increased by excessive iodine in both serum and liver in a dose-dependent manner, accompanying the decrease of hepatic D1 activity. That resulted in the increase of serum total thyroxine and the decrease of serum total triiodothyronine in iodine-loaded groups. The mRNA expression of SREBP-1c and FAS was increased in iodine-loaded groups in response to the change of serum triiodothyronine. Present findings demonstrated that iodine excess could dose dependently induce hepatic steatosis. Furthermore, our data suggested that the disturbance of thyroid hormone metabolism involving oxidative stress may play a critical role in iodine excess-induced hepatic steatosis.

Nonpeptidic angiotensin II AT1 receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles.

Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT1 receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT1 receptor binding affinity and high AT1 receptor selectivity over AT2 receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT1 IC50 = 3 nM, AT2 IC50 > 10,000 nM, PA2 = 8.51) and 11g (AT1 IC50 = 0.1 nM, AT2 IC50 = 149 nM, PA2 = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT1 receptor antagonists in spontaneous hypertensive rats.

Shift of pathways during initiation of thermophilic methanogenesis at different initial pH.

To investigate the metabolic pathways during the initiation of methanogenesis from acid crisis, the influence of initial pH (5.0-6.5) on thermophilic methanogenic conversion of 100mmol/L acetate was monitored based on the isotopic signature and selective-inhibition method combined with analysis of the microbial structure. The results showed, lower pH extended the lag phase for methanogenesis which was inhibited at pH5.0 throughout the incubation. At initial pH6.0-6.5, methanogenesis was primarily initiated via acetoclastic methanogenesis (AM), with the fraction of the hydrogenotrophic pathway (f(mc)) accounting for 21-22% of total methane formation. Conversely, at initial pH5.5, the dominant pathway shifted to syntrophic acetate oxidation coupled with hydrogenotrophic methanogenesis (SAO-HM), with f(mc) rising to 51% and the abundance of syntrophic acetate-oxidizing bacteria increasing remarkably. Methanogenesis could initiate independently via SAO-HM pathway when AM pathway was inhibited. Acetate-oxidizing syntrophs could function as the initiation center of methanogenesis from low-pH crisis.

Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazole derivatives as nonpeptidic angiotensin II AT1 receptor antagonists.

A series of 6-substituted aminocarbonyl benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed nanomolar AT(1) receptor binding affinity and good AT(1) receptor selectivity over AT(2) receptor for all compounds of the series, a potent antagonistic activity in isolated rabbit aortic strip functional assay for compounds 6b, 6d and 6i was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6i is an orally active AT(1) receptor antagonist with low toxicity.

Quantification of the inhibitory effect of methyl fluoride on methanogenesis in mesophilic anaerobic granular systems.

The inhibitory effect of CH(3)F on methanogenesis in mesophilic anaerobic granules was tested at different concentrations (0-10% v/v, in the gas phase) and verified by the stable carbon isotopic signatures of CH(4) and CO(2). The results showed that the inhibitory effect increased with the initial CH(3)F concentration up to 5%. The CH(3)F concentration causing 50% metabolic inhibition was 0.32%. Complete inhibition of acetoclastic methanogenesis with a 91% reduction in total methanogenic activity was achieved when 5% CH(3)F was initially added to the headspace, which resulted in 870 µM dissolved CH(3)F in the liquid. It was much higher than that applied in other natural anoxic non-granular systems, indicating that the layered granular structure influenced the inhibitory effect. The obvious increase in hydrogen content indicated that high concentrations of CH(3)F (≥5%) suppressed hydrogenotrophic methanogenesis as well. The stable inhibition lasted for at least 6d as the CH(3)F concentration decreased slowly with incubation time. These results suggested that CH(3)F could be used for investigating methanogenic processes in anaerobic granular systems after the CH(3)F concentration and incubation time for specific inhibition of acetoclastic methanogenesis were carefully determined. In the present system, CH(3)F concentration of 5% was suggested to be optimal.