Combination of cetuximab with met inhibitor in control of cetuximab-resistant oral squamous cell carcinoma.

Objective: To investigate the underlying molecular mechanisms contributing to oral squamous cell carcinoma (OSCC) cell resistance to the epidermal growth factor receptor (EGFR) inhibitor. Materials and methods: OSCC cell lines HSC-2 and HSC-3 were assessed in vitro for drug treatment, cell viability, and gene expression and the online gene expression in OSCC tissues was analyzed for association with OSCC prognosis. Results: HSC-2 and HSC-3 cells expressed high EGFR levels, but hepatocyte growth factor (HGF) treatment induced cetuximab resistance, whereas the Met inhibitor PHA-665752 as well as Met siRNA was able to restore OSCC cell sensitivity to cetuximab. HGF treatment induced tumor cells to express p-Akt and p-ERK1/2. In contrast, the activity of Akt and ERK1/2 was suppressed by treatment with PHA-665752, Met siRNA, or their combination. Furthermore, Met was highly expressed in OSCC tissues and associated with a poor patient survival, while Met/HGF-activated Akt also was associated with a poor patient survival. Conclusions: This study demonstrates that Met/HGF expression results in OSCC resistance to cetuximab and tumor recurrence after cetuximab therapy; thus, inhibition of Met/HGF activity could restore OSCC sensitivity to cetuximab.

Preparation and properties of microfibrillated cellulose with different carboxyethyl content.

Carboxyethyl reaction was used as a pretreatment method before grinding and homogenization to prepare microfibrillated cellulose (MFC). The effect of carboxyethylation on the properties of cellulose materials and prepared MFC samples were investigated. Results showed that cellulose materials with different carboxyethyl content were obtained by controlling the chemical dosage. This reaction increased the water retention value, decreased the degree of polymerization and crystallinity, and changed the crystalline structure of cellulose. After pretreatment, the cellulose fibers were easier to be swelled and fibrillated, which greatly reduces the frequency of grinding. In addition, the diameter of the produced MFC decreased with the increase of carboxyl content. The charge density, suspension stability and transparency of MFC increased obviously due to the presence of carboxyethyl groups. This study provides a comprehensive understanding of carboxyethyl pretreatment for the preparation of MFC, which may help to enrich and promote the preparation and application of MFC.

Brazilian Green Propolis Improves Antioxidant Function in Patients with Type 2 Diabetes Mellitus.

Propolis contains a variety of bioactive components and possesses many biological properties. This study was designed to evaluate potential effects of Brazilian green propolis on glucose metabolism and antioxidant function in patients with type 2 diabetes mellitus (T2DM). In the 18-week randomized controlled study, enrolled patients with T2DM were randomly assigned to Brazilian green propolis group (900 mg/day) (n = 32) and control group (n = 33). At the end of the study, no significant difference was found in serum glucose, glycosylated hemoglobin, insulin, aldose reductase or adiponectin between the two groups. However, serum GSH and total polyphenols were significantly increased, and serum carbonyls and lactate dehydrogenase activity were significantly reduced in the Brazilian green propolis group. Serum TNF-α was significantly decreased, whereas serum IL-1ß and IL-6 were significantly increased in the Brazilian green propolis group. It is concluded that Brazilian green propolis is effective in improving antioxidant function in T2DM patients.

Integrated hot-compressed water and laccase-mediator treatments of Eucalyptus grandis fibers: structural changes of fiber and lignin.

Eucalyptus grandis fibers were treated with hot-compressed water (HCW) and laccase mediator to enhance the fiber characteristics and to produce an active lignin substrate for binderless fiberboard production. The composition, morphology, and crystallinity index (CrI) analysis of fibers showed that the HCW treatment increased the CrI and lignin content of the treated fibers through partial removal of hemicelluloses. Simultaneously, the HCW treatment produced some granules and holes on the surface of the fibers, which possibly facilitated the accessibility of the laccase mediator. Milled wood lignins and enzymatic hydrolysis lignins isolated from the control and treated fibers were comparatively characterized. A reduction of molecular weight was observed, which indicated that a preferential degradation of lignin occurred after exposure to the laccase mediator. Quantitative (13)C, 2D-HSQC and (31)P NMR characterization revealed that the integrated treatment resulted in the cleavage of ß-O-4' linkages, removal of G' (oxidized α-ketone) substructures, and an increase in the S/G ratio and free phenolic hydroxyls.

[Association study of CNR1, GAD1 and BDNF polymorphisms with male heroin dependence in the Dai population in Yunnan].

In order to analyze the association of CNR1(Cannabinoid receptor 1), GAD1(Glutamate decarboxylase 1), and BDNF(Brain-derived neurotrophic factor) polymorphisms with male heroin dependence in the Dai population in Yunnan Province, an eight-SNP co-amplification protocol was established to genotype on the SNaPshot platform. A case-control study was performed with 8 SNPs from CNR1, GAD1, and BDNF genes in 165 heroin-dependent males and 170 healthy males of the Dai population. Statistical analyses were conducted with SPSS17.0, Haploview4.2, PHASE2.1, and MDR software. We found that: (1) the genotype frequency of rs13306221 was significant in the case group (P<0.025); (2) the A allelic frequency of rs6265 was significantly higher in the case group; (3) the haplotypes of T-A-C, C-C-C, C-C-T, and T-C-C based on rs1978340-rs3791878-rs11542313 and haplotype A-G based on rs6265-rs13306221 were significant (P<0.05); (4) the haplotype frequencies of T-A-C, C-C-T, and A-G were significantly higher in the case group. These results indicate that the linkage between rs1978340 and rs3791878 in GAD1 has a strong association with heroin dependence. Furthermore, polymorphisms in CNR1 (rs1049353), GAD1 (rs1978340 and rs11542313), and BDNF (rs6265 and rs13306221) were associated with heroin dependence in the Yunnan Dai population, and individuals with the rs6265 A allele were more likely to be heroin dependent.

Brazilian green propolis improves immune function in aged mice.

Aging weakened innate and adaptive immunity both quantitatively and qualitatively. Some components in propolis could stimulate immune function in young animals or cultured immune cells in vitro. Few studies had been carried out in the aged. The present study was to evaluate the effects of Brazilian green propolis supplementation on the immunological parameters in aged mice. Eighty Kunming mice, aged 15-18 months, were randomly assigned to the control and three experimental groups supplemented with different doses (83.3, 157.4 and 352.9 mg/kg.bw respectively) of Brazilian green propolis. The experiment lasted for 4 weeks. Contents of total polyphenol, flavonoid, cinnamic acid and artepillin-C in Brazilian green propolis were analyzed. Splenic NK cytotoxic, T lymphocyte proliferation and antibody generation cells, as well as the phagocytosis of peritoneal macrophages, ear swelling, and serum contents of IgG, IgM, hemolysin and cytokines were measured. After 4 weeks of treatment, the phagocytosis of peritoneal macrophages was enhanced in 157.4 mg/kg and 352.9 mg/kg groups. Ear swelling increased in all propolis treatmented groups. Antibodies specific to sheep erythrocytes were higher in the groups receiving 157.4 and 352.9 mg/kg.bw than that of control group. IgG level dramatically increased in the groups receiving 83.3 and 157.4 mg/kg.bw in comparison to the control group. These results indicate that administration of Brazilian green propolis have a positive effect on innate and adaptive immunity in aged mice.

No correlation is found for vegetables between antioxidant capacity and potential benefits in improving antioxidant function in aged rats.

Vegetables vary greatly in antioxidant capacity in vitro. This study was to investigate the actions of three vegetables different remarkably in antioxidant capacity in vitro on antioxidant function in aged rats. Sixty female aged Wistar rats were randomly assigned to the control, lotus root, rape and cucumber (high, moderate and low in antioxidant capacity, respectively) treated groups. After 6 weeks of feeding, there were no significant differences in plasma FRAP value and contents of vitamin C, vitamin E, uric acid and total phenolics among different groups, whereas the content of reduced glutathione was significantly higher in the rape and cucumber groups. Plasma superoxide dismutase activity also was significantly increased in the rape and cucumber groups. Plasma contents of malondialdehyde, carbonyls and hemolysis were decreased significantly in 3 vegetable-treated groups. Meanwhile, urinary 8-hydroxy-2'-deoxyguanosine excretion was lower significantly in the rape group and the ratio of comet tail length to total length of blood mononuclear cells was decreased significantly in 3 vegetables treated groups. These results suggest that 3 vegetables tested are effective in improving antioxidant function to some extent in aged rats and no correlation is found between antioxidant capacity in vitro and improvements of antioxidant function. The benefits observed in this study may come from additive or synergistic combinations of antioxidants contained in vegetables.

Preparation and Characterization of Lignocellulosic Oil Sorbent by Hydrothermal Treatment of Populus Fiber.

This study is aimed at achieving the optimum conditions of hydrothermal treatment and acetylation of Populus fiber to improve its oil sorption capacity (OSC) in an oil-water mixture. The characteristics of the hydrolyzed and acetylated fibers were comparatively investigated by FT-IR, CP-MAS 13C-NMR, SEM and TGA. The optimum conditions of the hydrothermal treatment and acetylation were obtained at170 °C for 1 h and 120 °C for 2 h, respectively. The maximum OSC of the hydrolyzed fiber (16.78 g/g) was slightly lower than that of the acetylated fiber (21.57 g/g), but they were both higher than the maximum OSC of the unmodified fiber (3.94 g/g). In addition, acetylation after hydrothermal treatment for the Populus fiber was unnecessary as the increment of the maximum OSC was only 3.53 g/g. The hydrolyzed and the acetylated Populus fibers both displayed a lumen orifice enabling a high oil entrapment. The thermal stability of the modified fibers was shown to be increased in comparison with that of the raw fiber. The hydrothermal treatment offers a new approach to prepare lignocellulosic oil sorbent.

Quercetin reduces serum homocysteine level in rats fed a methionine-enriched diet.

OBJECTIVE: The aim of this study was to determine the effects of quercetin on homocysteine (Hcy) metabolism and hepatic antioxidant status in high methionine (Met)-fed rats. METHODS: Rats were fed for 6 wk the following diets: control, 1.0% Met, 1.0% Met and 0.1% quercetin, 1.0% Met and 0.5% quercetin, 1.0% Met and 2.5% quercetin-supplemented diets. Serum Hcy, Met, cysteine, serine, taurine, glutathione (GSH), quercetin and its metabolites, and activities of alanine transaminase (ALT) and aspartate transaminase (AST) were assayed. Hepatic malondialdehyde, GSH and carbonyls, and activity of superoxide dismutase and ferric-reducing antioxidant power also were measured. RESULTS: Serum Hcy was increased significantly after Met treatment and decreased after quercetin supplementation. Meanwhile, serum taurine was increased and serine decreased. However, the content of GSH in serum and liver was decreased in the quercetin-supplemented groups and activities of serum ALT and AST were enhanced in the 1.0% Met and 2.5% quercetin-supplemented groups. CONCLUSIONS: Quercetin is effective in decreasing serum Hcy level in high Met-fed rats and one of possible mechanisms is associated with increased transsulfuration of Hcy. Quercetin can acts as a prooxidant at high intake levels.

Quercetin alters energy metabolism in swimming mice.

Quercetin has been demonstrated to be effective in increasing physical endurance in mice and humans. However, the mechanisms involved are not fully understood. In this study, male Kunming mice were fed a diet containing 0.1% quercetin for 14 days before swimming for 60 min. The overall serum metabolic profile was investigated by a ¹H nuclear magnetic resonance-based metabolomic approach. Serum glucose, lactate, nonesterified fatty acids (NEFA), and nonprotein nitrogen (NPN), as well as hepatic and muscular glycogen were measured biochemically. The results of metabolomic analysis showed that swimming induced a significant change in serum metabolic profile. Relative increases in the levels of lactate, alanine, low-density lipoprotein-very low-density lipoprotein, and unsaturated fatty acids, and decreases in choline, phosphocholine, and glucose were observed after swimming. With quercetin supplementation, these changes were attenuated. The results of biochemical assays were consistent with the data obtained from metabolomic analysis, in that serum NEFA was increased while lactate and NPN decreased after exposed to quercetin in swimming mice. Similar change in NEFA was also found in liver and gastrocnemius muscle tissues. Our current findings suggest that quercetin alters energy metabolism in swimming mice and increased lipolysis may contribute to the actions of quercetin on physical endurance.

[Improvement effect of vitamins B1, B2 and PP supplementation on substance metabolism of mice exposed to acute hypoxia].

OBJECTIVE: To explore the improvement effect of vitamins B1, B2, PP supplementation to the metabolism changes of carbohydrates, lipids, protein and energy in mice exposed to acute hypoxia. METHODS: Fifty male Kunming mice were randomly divided into normal, acute hypoxia, acute hypoxia plus 2 times, 4 times and 8 times vitamins B1, B2, PP supplemented groups. All mice were fed corresponding diets for two weeks and then except the normal group were exposed to a simulated altitude of 6 000 meters for 8 hours. The changes of glucose, pyruvate, lactate, urea nitrogen, free fatty acids and beta-hydroxybutyric acid from serum, liver glycogen and blood adenosine triphosphate (ATP) concentration were measured. RESULTS: After being exposed to acute hypoxia, the mice glucose, liver glycogen, pyruvate, lactate, free fatty acids, beta-hydroxybutyric acid and urea nitrogen level were increased significantly (P < 0.05), while blood ATP concentration was decreased. In the vitamins B1, B2 and PP supplemented groups, these changes were improved. CONCLUSION: The significant changes in carbohydrate, lipid and protein metabolism were observed in mice exposed to acute hypoxia, and the supplementation of vitamins B1, B2 and PP was proved to be beneficial in improving some metabolic pathways. It is suggested that the supplemented dose of four times was good.

Dietary quercetin supplementation increases serum antioxidant capacity and alters hepatic gene expression profile in rats.

The aim of this study was to determine the effect of quercetin on hepatic gene expression profile in rats. Twenty male Wistar rats were divided into the control group and the quercetin-treated group, in which a diet containing 0.5% quercetin was provided. After two weeks of feeding, serum and liver samples were collected. Biomarkers of oxidative stress, including serum ferric reducing antioxidant power (FRAP) values and levels of ascorbic acid, vitamin E (VE), glutathione (GSH) and malondialdehyde (MDA) were measured. The hepatic gene expression profile was examined using a microarray technique. The results showed that serum FRAP value, levels of ascorbic acid and VE were increased significantly, whereas serum levels of GSH and MDA were not changed significantly after quercetin supplementation. The microarray analysis revealed that some hepatic genes involved in phase 2 reaction, metabolism of cholesterol and homocysteine, and energy production were expressed differentially in response to quercetin administration. These findings provide a molecular basis for the elucidation of the actions played by quercetin in vivo.

[The metabolic changes of mice serum after loaded swimming].

OBJECTIVE: To investigate the metabolic changes of mice serum after loaded swimming and to provide a basis for the study of anti-fatigue functional food. METHODS: The male Kunming mice were randomly divided into four group, fed an AIN-93 diet for 14 days, and forced to swim for 30, 60 or 120 min, respectively, with a load on their tails. The mice were executed after swimming immediately and the changes of serum metabolic profiles were analyzed using metabolomic approach. The spectrum was acquired by using Carr Purcell Meiboom Gill (CPMG) or Longitudinal Eddy Current Delay (LED) sequence, and transformed into 1H NMR spectrogram via Fourier transformation. All the data were analyzed by principal component analysis by using the SIMCA-P+ software. RESULTS: The serum metabolic profiles changed significantly after loaded swimming. Serum beta-hydroxybutyric acid, acetate, lactate, lipid were increased and glucose, choline, phosphorylcholine, alanine and phosphatidylcholine decreased. These changes were time dependent. CONCLUSION: The changes of serum metabolic profiles after loaded swimming were time dependent, especially for lipid metabolite.Further study based on the interaction of choline and lipid metabolism may contribute to understand the mechanism of fatigue.

Cholesterol metabolism is modulated by quercetin in rats.

Quercetin has attracted much attention recently because of its antioxidant capacity and potential in the prevention of chronic degenerative diseases. However, its actions and the mechanisms involved are not completely understood. In this study, male Wistar rats were fed a diet containing 0.5% quercetin for 14 days. Serum samples were collected at the end of the experiment, and the overall serum metabolic profile was investigated by (1)H nuclear magnetic resonance (NMR)-based metabolomic analysis. Remarkable changes in the serum metabolic profile were manifested with the relative increase in the levels of lactate and low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and reduction in glucose, high-density lipoprotein (HDL), and some amino acids after quercetin exposure. Biochemical measurements confirmed that the serum low-density lipoprotein cholesterol (LDL-C) level was increased significantly after quercetin treatment. Our current findings indicate that quercetin can induce a remarkable change in cholesterol metabolism. Further studies are needed to investigate the molecular mechanisms and the possible links to the health effects or toxic actions of quercetin.

Antioxidant capacity of different fractions of vegetables and correlation with the contents of ascorbic acid, phenolics, and flavonoids.

The antioxidant capacity of different fractions of 17 vegetables were analyzed using ferric reducing antioxidant power assay (FRAP assay) after water and acetone extractions. The contents of ascorbic acid, phenolics, and flavonoids were determined and their correlations with FRAP value were investigated. The results showed that the peel or leaf fractions of vegetables were stronger than the pulp or stem fractions in antioxidant capacity based on total FRAP value. Lotus root peel was the highest and cucumber pulp the lowest in total FRAP value among the vegetable fractions analyzed. All water extracts were higher in FRAP value than the acetone extracts. The FRAP value was significantly correlated with the contents of ascorbic acid, phenolics, or flavonoids in water extracts, in which the phenolics contributed most based on multivariate regression analysis. We conclude that different vegetable fractions were remarkably different in antioxidant capacity. The phenolics are responsible mostly for the antioxidant capacity of vegetables in vitro.

Metabolomic study on vitamins B1, B2, and PP supplementation to improve serum metabolic profiles in mice under acute hypoxia based on ¹H NMR analysis.

OBJECTIVE: To explore metabolic changes after acute hypoxia and modulating effect of vitamins B1, B2, and PP supplementation in mice exposed to acute hypoxia. METHODS: Fifty male Kunming mice were randomly divided into 5 groups: normal, acute hypoxia, acute hypoxia with 2, 4 and 8 time-vitamins B1, B2, and PP supplementation. All mice were fed with corresponding diets for two weeks and then were exposed to a simulated altitude of 6,000 meters for 8 h, except for the normal group. Nuclear magnetic resonance analysis was used to identify the changes of serum metabolic profiles. RESULTS: There were significant changes in some serum metabolites under induced acute hypoxia, essentially relative increase in the concentrations of lactate, sugar and lipids and decrease in ethanol. The serum levels of choline, succinate, taurine, alanine, and glutamine also increased and phosphocholine decreased in the acute hypoxia group. After vitamins B1, B2, and PP supplementation, all these metabolic changes gradually recovered. CONCLUSIONS: Significant changes in serum metabolic profile were observed by metabolomics in mice exposed to acute hypoxia, and vitamins B1, B2, and PP supplementation proved to be beneficial to improving some metabolic pathways. It is suggested that the dietary intakes of vitamins B1, B2, and PP should be increased under hypoxia condition.

[Effects of soybean isoflavones on the cell cycles, the cell apoptosis and the proliferation of spleen in radiated mice].

AIM: To study effect of soybean isoflavones (SI) on spleen in radiated mice. METHODS: 90 male mice were randomly divided into control group, radiated group, radiated plus 0.5% dose SI group. After 2-week feeding, the mice received 4.0 Gy 137Cs gamma-radiation, the cell cycles, cell apoptosis and proliferation on the spleen and the spleen index were observed in radiated after 12 h, 24 h, 1 week and 2 weeks. RESULTS: After the mice were radiated, the spleen were significantly atrophy, the rate of the cell apoptosis and the cell cycles of G0-G1 phase in splenocytes were significantly increased (P < 0.01), the cell cycles rate of S phase and the proliferation index were significantly decreased in spleen (P < 0.05). Compared with radiated group, the spleen atrophy and the rate of the cell cycles of G0-G1 phase were significantly decreased (P < 0.05), and the cell cycles of G2-M phase and the proliferation index were significantly increased (P < 0.05) in the mice supplied 0.5% soybean isoflavones. CONCLUSION: The soybean isoflavones could significantly increase spleen radioprotective effect in mice.