[Epidemiological research progress on the relationship between children's dietary patterns and health].

As food preferences and eating habits form early in life, the development of healthy eating habits in early childhood is a way to prevent diet-related diseases. The dietary pattern approach examines the effect of an overall diet on health outcomes, instead of individual foods or nutrients, thereby presenting a comprehensive evaluation of children's dietary intake. This article reviews the current literature to summarize the main methods for assessing dietary patterns and explore relationships between children's dietary patterns and obesity, puberty onset, cardiovascular diseases, and neurodevelopment. The purpose of this review is to provide evidence-based support for reducing the risk of diet-related diseases in children and recommendations for future research directions.

Toxicity of Mycotoxins from Contaminated Corn with or withoutYeast Cell Wall Adsorbent on Broiler Chickens.

This study investigated the effects of feeds naturally contaminated with mycotoxins on growth performance, serum biochemical parameters, carcass traits, and splenic heat shock protein 70 (Hsp70) mRNA expression levels in broiler chickens. The efficacy of yeast cell wall (YCW) adsorbent in preventing mycotoxicosis was also evaluated. Three hundred 1-d-old Arbor Acres broiler chicks were randomly allotted to 3 treatments in completely randomized design for 42 d. Each treatment group had 5 replicate pens with 20 birds. The treatments were as follows: i) basal diet (control), ii) naturally contaminated diet (NCD), and iii) NCD+0.2% YCW adsorbent (NCDD). The NCD decreased average daily gain (ADG) (p<0.01) of 0 to 21 d, 22 to 42 d, and 0 to 42 d, and increased feed conversion ratio (p<0.01) of 22 to 42 d and 0 to 42 d. Both the breast meat percentage and thigh meat percentage of the NCD group were significantly higher (p<0.01) than that of the control group on d 21. The NCD group showed significantly increased levels of triglycerides (p<0.05) and cholesterol (p<0.05) on both d 21 and d 42 compared to the control group. However, the NCD significantly reduced (p<0.01) the high-density lipoprotein (HDL) on d 42 compared to controls. Compared with the NCD, supplementation with YCW significantly improved (p<0.01) the ADG of 0 to 21 d and 0 to 42 d, and increased (p<0.01) concentrations of HDL on d 42, and on d 21, and triglycerides (p<0.05) on d 21 and d 42. Supplementation with YCW reduced (p<0.01) the breast meat percentage, the thigh meat percentage, the concentrations of cholesterol (p<0.01) and the low-density lipoprotein (p<0.05) on d 21, and improved (p<0.01) the splenic Hsp70 mRNA expression levels compared with the NCD group. The results of this study indicated that feeding NCD for 42 d had adverse effects on broiler chickens, and that YCW might be beneficial in counteracting the effects of mycotoxins.

Effects of naturally mycotoxin-contaminated corn on nutrient and energy utilization of ducks fed diets with or without Calibrin-A.

One hundred sixty-two 21-d-old ducks were randomly allotted to 6 treatments with 3 levels of mycotoxin-contaminated corn (0, 50, and 100% M) and 2 levels of Calibrin-A (CA, a clay mycotoxin adsorbent, 0 and 0.1%) to evaluate the effects of increasing levels of mycotoxin-contaminated corn on nutrient utilization in ducks fed diets with or without CA. Endogenous losses were obtained from another 27 ducks. Excreta samples were collected to determine DM, OM, CP, amino acids, and gross energy. Gross energy was analyzed for computation of AME and TME. The apparent digestibility (AD) and true digestibility (TD) of the nutrients in all treatments with and without CA had common (P > 0.05) intercepts and slopes except Pro (P < 0.05). The AME, TME, AD, and TD of DM, OM, Phe, and Gly were linearly (P < 0.05) decreased as the concentration of contaminated corn in the diet increased. Ducks fed the 100% M diet supplemented with 0.1% CA increased AD and TD of Gly compared with the 100% M diet, and ducks fed 50 and 100% M diet supplemented with 0.1% CA increased AD and TD of Pro compared with 50% M and 100% M diet, respectively. In the present study, ducks fed mycotoxin-contaminated corn decreased nutrient digestibility in dose-dependent manner, and 0.1% CA supplementation improved AD and TD of Gly and Pro.

Effects of Astragalus membranaceus root processed to different particle sizes on growth performance, antioxidant status, and serum metabolites of broiler chickens.

The objectives of this study were to assess the effects of supplementation of Astragalus membranaceus root powder (AMP) and AMP processed to different particle sizes on growth performance, antioxidant status, and serum metabolites of broiler chickens. The experiment was conducted with one hundred twenty 1-d-old Arbor Acres broilers in 5 groups of 4 cages and for both starter (0 to 21 d) and grower (22 to 42 d) phases. The treatments were basal diet only (control) and basal diet supplemented with 5 g/kg of diet of AMP processed to particle sizes of 300, 149, 75, or 37 µm. Average daily gain, ADFI, and feed conversion rate (FCR) were determined weekly, and carcass yield, serum antioxidant enzyme activity, and metabolites were determined at 21 and 42 d of the experiment. Supplementation of AMP increased (P < 0.01) activities of total superoxide dismutase (TSOD) and glutathione peroxidase (GSHPx), but reduced (P < 0.01) concentrations of malondialdehyde (MDA) and cholesterol in the serum of chickens at 21 and 42 d. Reducing AMP particle sizes from 300 to 37 µm linearly increased (P < 0.01) TSOD and GSHPx activities at 21 and 42 d, but linearly decreased (P < 0.01) MDA at 42 d. Concentrations of total protein, albumin, and globulin in the serum were also increased (P < 0.05) or tended to be increased (P = 0.05 to 0.10) by AMP and linearly increased (P < 0.01) as the AMP particle sizes decreased. However, both treatments had no effect on ADG, ADFI, or FCR throughout the entire experiment period, although carcass yield increased (P < 0.05) at 42 d. Dietary supplementation of AMP at the concentration of 5 g/kg of diet enhanced serum antioxidant status and its efficacy linearly increased as the AMP particle size decreased from 300 to 37 µm, but had no effect on growth performance of broilers.

Toxicity of increasing aflatoxin B1 concentrations from contaminated corn with or without clay adsorbent supplementation in ducklings.

A total of 1,280 1-d-old ducks were used in a study to investigate the effects of increasing aflatoxin B1 (AFB1) concentrations from naturally contaminated corn on young ducklings, and the effectiveness of a clay adsorbent (CA) to protect against those effects. Ducks were randomly allotted to 8 treatments (TRT) in a 4 × 2 factorial arrangement with 4 levels of AFB1 (0, 25, 50, and 100 µg/kg) and 2 levels of CA (0 and 0.1%) with 8 pens per TRT and 20 ducks per pen. All ducks were allowed ad libitum access to feed and water during the 21-d experiment. The ADG, ADFI, feed conversion rate, mortality, bill color, and CV of BW of each replicate were measured at the end of the study. Blood and tissue samples from 8 ducks per TRT were obtained on d 21 of the experiment to determine the serum immunoglobulin and protein concentrations, relative organ weights, and intestinal morphology. Average daily gain and relative weights of the liver, spleen, thymus, and bursa of Fabricius decreased linearly (P < 0.05) as dietary AFB1 increased. Serum proteins and intestinal villi heights and villus/crypt ratio followed the same pattern. Bill decolorization ratio, CV of BW, and mortality increased linearly (P < 0.05) as dietary AFB1 increased. Adding 0.1% CA to the diet improved (P < 0.05) the relative weights of the small intestine, spleen, and thymus, and the villus height and villus/crypt ratio of the duodenum and jejunum, as well as the serum IgG and IgM concentrations. Adding CA also reduced (P < 0.05) bill decolorization ratio, CV of BW, mortality, and serum IgA concentration. Therefore, duck performance was negatively affected by increasing AFB1 concentrations in diets. But the addition of 0.1% CA can protect against the detrimental effects caused by AFB1-contaminated corn in diets for ducks.

Effects of ginger root (Zingiber officinale) on laying performance and antioxidant status of laying hens and on dietary oxidation stability.

To investigate the effects of ginger root (Zingiber officinale) on laying performance and antioxidant status of laying hens and on dietary oxidation stability, 675 Hy-Line brown laying hens at 27 wk of age were randomly allocated to 5 treatments with 5 replicates in a complete randomized design. Laying hens were fed corn-soybean meal based diets and supplemented with 0, 5, 10, 15, or 20 g of ginger powder/kg of diet for 10 wk. The ADFI, laying rate, average egg weight, egg mass, and feed conversion of each replicate were measured weekly. Blood samples from 10 laying hens and 15 egg samples/treatment were obtained on d 35 and 70 of the experiment to determine the serum or egg yolk antioxidant enzymatic activities. Three separate batches of each treatment diet were also made at the beginning of the experiment and stored at 20°C. Subsamples were taken at 10-d intervals to determine the dietary oxidation stability over a 60-d period. All laying hens had similar ADFI, laying rate, average egg weight, and feed conversion. However, laying hens supplemented with ginger powder had higher (P = 0.024) egg mass than the control group. Supplementation of ginger powder increased (P < 0.05) the serum and egg yolk antioxidant enzymatic activities of laying hens on d 35 and 70. Increasing ginger powder from 0 to 20 g/kg of diet linearly increased (P < 0.05) the peroxide value but linearly reduced (P < 0.05) the acid value of lipid extracted from stored diets for the first 30 d, but not for the second 30 d. Dietary supplementation of ginger powder improved laying performance and serum and egg yolk antioxidant status and enhanced dietary oxidation stability in a dose-dependent manner. The optimum supplementation rate of ginger powder in the diet of laying hens appeared to be between 10 and 15 g/kg of diet.

Positive association of up-regulated Cripto-1 and down-regulated E-cadherin with tumour progression and poor prognosis in gastric cancer.

AIMS: Cripto-1 may be capable of up-regulating signalling molecules associated with epithelial-to-mesenchymal transition (EMT), an important event characterized by loss of E-cadherin during malignant tumour progression and metastasis. The aim was to investigate the expression of Cripto-1 and E-cadherin in relation to clinicopathological features and patient prognosis of gastric cancer. METHODS AND RESULTS: The expression of Cripto-1 and E-cadherin was studied by immunohistochemistry in 118 gastric cancer cases. Up-regulated Cripto-1 (CR+) was found in 54% (64/118) of cases, whereas down-regulated E-cadherin (E-cad-) was found in 70% (83/118) of cases. Either CR+ or E-cad- was associated with lymph node metastasis, liver metastasis and late TNM stage (P < 0.05). Patients with either CR- or E-cad+ showed higher 5-year survival rates than those with CR+ or E-cad- (P = 0.0012 and P = 0.0017, respectively). When combined, evaluation of these two proteins, simultaneous CR+ and E-cad- (CR+/E-cad-) in cancer was strongly associated with the above three aggressive clinicopathological features (P < 0.001) and indicated the worst patient survival (P = 0.0001). Multivariate analysis revealed that CR+/E-cad- was an independent prognostic factor in gastric cancer. CONCLUSIONS: Combined analysis of Cripto-1 and E-cadherin has significant value in evaluating the metastatic potential of gastric cancer and predicting patient prognosis.

Effects of changes in stopping-power ratios with field size on electron beam relative output factors.

Stopping-power ratios are a function of field size and vary with accelerators. To investigate how these variations affect relative output factor measurements made using ion chambers for electron beams, especially for small fields, (L/rho)air(water) is calculated using the Monte Carlo technique for different field sizes, beam energies, and accelerators and is compared to the data in TG-21 or TG-25, which are for mono-energetic broad beams. For very small field sizes defined by cutouts, if the change in (L/rho)air(water) with dmax is ignored (i.e., TG-25 is not carefully followed), there is an overestimate of relative output factors by up to 3%. Ignoring the field-size effect on stopping-power ratio adds an additional overestimate of up to one-half percent, and using mono-energetic stopping-power ratio data instead of realistic beam data gives another error, but in the opposite direction, of up to 0.7%. Due to the cancellation of these latter two errors, following TG-25 with (L/rho)air(water) data for broad mono-energetic beams will give the correct answer for the ROF measurement within 0.4% compared to using (L/rho)air(water) data for which the field-size effect is considered for realistic electron beams.

Monte Carlo investigation of electron beam output factors versus size of square cutout.

A major task in commissioning an electron accelerator is to measure relative output factors versus cutout size (i.e., cutout factors) for various electron beam energies and applicator sizes. We use the BEAM Monte Carlo code [Med Phys. 22, 503-524 (1995)] to stimulate clinical electron beams and to calculate the relative output factors for square cutouts. Calculations are performed for a Siemens MD2 linear accelerator with beam energies, 6, 9, 11, and 13 MeV. The calculated cutout factors for square cutouts in 10 X 10 cm2, 15 X 15 cm2, and 20 X 20 cm2 applicators at SSDs of 100 and 115 cm agree with the measurements made using a silicon diode within about 1% except for the smallest cutouts at SSD= 115 cm where they agree within 0.015. The details of each component of the dose, such as the dose from particles scattered off the jaws and the applicator, the dose from contaminant photons, the dose from direct electrons, etc., are also analyzed. The calculations show that inphantom side-scatter equilibrium is a major factor for the contribution from the direct component which usually dominates the output of a beam. It takes about 6 h of CPU time on a Pentium Pro 200 MHz computer to simulate an accelerator and additional 2 h to calculate the relative output factor for each cutout with a statistical uncertainty of 1%.

Evaluation of a commercial three-dimensional electron beam treatment planning system.

We evaluated a commercial three-dimensional (3D) electron beam treatment planning system (CADPLAN V.2.7.9) using both experimentally measured and Monte Carlo calculated dose distributions to compare with those predicted by CADPLAN calculations. Tests were carried out at various field sizes and electron beam energies from 6 to 20 MeV. For a homogeneous water phantom the agreement between measured and CADPLAN calculated dose distributions is very good except at the phantom surface. CADPLAN is able to predict hot and cold spots caused by a simple 3D inhomogeneity but unable to predict dose distributions for a more complex geometry where CADPLAN underestimates dose changes caused by inhomogeneity. We discussed possible causes for the inaccuracy in the CADPLAN dose calculations. In addition, we have tested CADPLAN treatment monitor unit and electron cut-out factor calculations and found that CADPLAN predictions generally agree with manual calculations.

Nucleation and crystallization kinetics of hydrated amorphous lactose above the glass transition temperature.

The crystallization kinetics of amorphous lactose in the presence and absence of seed crystals were investigated at 57.5% relative humidity. Isothermal crystallization studies were conducted gravimetrically in an automated vacuum moisture balance at several temperatures between 18 and 32 degrees C. The crystallization rate constants were then determined from Johnson-Mehl-Avrami (JMA) treatment and isothermal activation energies were obtained from Arrhenius plots. Based on microscopic observations, a reaction order of 3 was used for JMA analysis. The nonisothermal activation energies were determined by differential scanning calorimetry using Kissinger's analysis. Isothermal activation energies for amorphous lactose with and without seed crystals were 89.5 (+/-5.6) kJ/mol and 186.5 (+/-17.6) kJ/mol, respectively. Nonisothermal activation energies with and without seed crystals were 71 (+/-7.5) kJ/mol and 80.9 (+/-8.9) kJ/mol, respectively. The similarity of the isothermal and nonisothermal activation energies for the sample with seeds suggested that crystallization was occurring by growth from a fixed number of preexisting nuclei. Markedly different isothermal and nonisothermal activation energies in the absence of seeds suggested a site-saturated nucleation mechanism, and therefore allowed calculation of an activation energy for nucleation of 317 kJ/mol.

Physical properties of parabens and their mixtures: solubility in water, thermal behavior, and crystal structures.

The peculiar solubility behavior of propylparaben (propyl ester of 4-hydroxybenzoic acid) in aqueous solution, when tested separately and together with methyl-, ethyl-, and butyl-parabens, has been investigated in detail. The results clearly indicate that the decrease in solubility (approximately 50% compared to the solubility value of propylparaben alone) is typical of those mixtures containing also ethylparaben, as demonstrated by solubility experiments on binary, ternary, and quaternary mixtures of the parabens. Phase diagrams of all the six binaries show that propylparaben and ethylparaben are the only pair that form almost ideal solid solutions near the melting temperatures. Moreover, phase-solubility analysis shows that propylparaben and ethylparaben, at room temperature, can also form solid solutions whose solubility is related to the composition of the solid phase at equilibrium. To achieve an independent confirmation of the possible solid solution formation that supports the above interpretation of the solubility behavior, the crystal structures of the four parabens have been examined and isostructurality has been found to exist only between ethylparaben and propylparaben. Powder X-ray diffraction has also been performed on ethylparaben, propylparaben, and their solid solutions obtained by recrystallization from water. The progressive shift of distinctive diffraction peaks with phase composition clearly indicates that propylparaben and ethylparaben form substitutional solid solutions. The small value (<1) of the disruption index provides thermodynamic support for substitutional solid solutions based on isostructural crystals.

Pharmacokinetic study of orally administered RU 486 in non-pregnant women.

A method based on HPLC was devised for the estimation of RU 486 in blood and utilised to study the pharmacokinetics of a single dose of 50 mg RU 486 administered orally to 12 women on day 7 of the cycle. The dose was rapidly absorbed with peak plasma concentration between 1 and 2 hours. Distribution was also rapid (mean t1/2 alpha: 1.4h), whereas elimination was slow (mean t1/2 beta: 28.3 h). RU 486 was still detectable in some women at 72 h after administration. The plasma concentrations fitted the equation for a two-compartment open model from which the pharmacokinetic parameters were calculated. The mean total plasma clearance was 3.0 l/h, and the comparison of our data with those published studies suggests that the pharmacokinetics of RU 486 in Chinese women are similar to those of other populations.

PIP: A method based on high performance liquid chromatography (HPLC) was developed for the estimation of RU-486 in blood and used to analyze the pharmacokinetics of a single dose of 50 mg of RU-486 administered orally to 12 Chinese women on day 7 of the menstrual cycle. In the 1st 6 subjects, blood samples were taken immediately before and 1, 2, 4, 8, 24, and 48 hours after RU-486 administration; in the 2nd group of 6 women, additional samples were taken at 0.33, 0.5, 0.75, and 72 hours. Since there were no significant differences between the 2 groups in values, the data were combined. RU-486 was found to be rapidly absorbed, with significant amounts present in the 20 minute samples and peak concentrations at 1-2 hours. In contrast, elimination was slow and significant levels of RU-486 were still detectable in most subjects at 72 hours. The mean value for the half-life of absorption was less than 1 hour, while the mean half-life of distribution was 1.4 hours. Mean total plasma clearance was 3.0 liters/hour. The plasma concentrations fitted the equation for a 2-compartment open model from which the pharmacokinetic parameters were calculated. Comparison of these findings with those from other studies suggest that the pharmacokinetics of RU-486 in Chinese women are similar to those in non-Asian populations.

Incorporation mechanism of guest molecules in crystals: solid solution or inclusion?

Guest molecules (impurities or additives), together with some crystallization solvent, are often incorporated into the host crystals during crystallization from solution. The guest molecules may be incorporated either in solid solution or in liquid inclusions, or by both mechanisms. The mechanism of guest incorporation has been examined by a simple calculation method which is based on the equality of the guest/solvent mole ratio in the initial crystallization medium and in the putative inclusions. Application of this calculation method to eight guest+host systems described in the literature has shown that a negligible amount (at most 0.2%) of the guest molecules is incorporated into the crystal lattice in liquid inclusions. Therefore, it is concluded that the vast majority of the guest molecules are incorporated into the crystals in solid solution, as previously suggested, but hitherto unproven, for these guest-host systems.

Enhancing the bioavailability of ABT-963 using solid dispersion containing Pluronic F-68.

Solid dispersions using Pluronic F-68 as a carrier were studied for improving the dissolution and bioavailability of ABT-963, a poorly water-soluble compound. The solid dispersions were prepared either by evaporation of the ethanol solutions containing ABT-963 and Pluronic, or by cooling the hot melt of the drug in the carrier. The dispersions were characterized using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy, elemental mapping, and by constructing the melting point phase diagram. In vitro dissolution and in vivo oral bioavailability in fasted dogs were compared for the solid dispersion and a conventional IR capsule formulation. Results showed that, at a composition of approximately 7.5%, ABT-963 formed a eutectic mixture with Pluronic F-68. Both the drug and the polymer were crystalline in the solid dispersion with a wide range of composition of each component. The solid dispersion substantially increased the in vitro dissolution rate of ABT-963. Dosing of the dispersion to fasted dogs resulted in a significant increase of oral bioavailability compared with the conventional IR capsule formulation. These results show that solid dispersion is a promising approach for developing ABT-963 drug products.

Presence of antibodies to heat stress proteins and its possible significance in workers exposed to high temperature and carbon monoxide.

Antibodies to the ubiquitous group of stress proteins known as heat shock proteins (Hsps) have been found to be associated with a number of diseases in humans. Hsps are known to be induced by certain xenobiotics, some of which are common in the working environment. The biological significance of the presence of such autoantibodies is presently unclear. In the present study, we used immunoblotting to investigate the presence of antibodies against the different stress proteins, Hsp27, Hsp60, Hsp71, Hsc (heat shock cognate) 73 and Hsp89 alpha and beta in groups of workers exposed to high temperature or carbon monoxide. These data were related to a detailed clinical evaluation and to various laboratory measurements including electrocardiogram (ECG), B echogram, white blood cell counts and typing, the activity of alanine aminotransferase (ALT), acid phosphatase (ACP) and alkaline phosphatase (ALP) and lymphocyte DNA damage. Antibodies to Hsp27 and Hsp71 were found more frequently in the high temperature and carbon monoxide-exposed groups than in controls (P < 0.05). The carbon monoxide-exposed group showed the highest incidence of anti-Hsp antibodies. Anti-Hsp60 antibodies were only detected in workers exposed to high temperature or carbon monoxide. The percentage of workers with abnormal ECG, B echogram changes and displaying hepatitis B antigen (HBsAg) was higher in the carbon monoxide group than in the control group (P < 0.05). There was a significant increase in the activity of ALT in the high temperature and carbon monoxide groups and in the activities of ACP and ALP in the carbon monoxide group (P < 0.05). The extent of DNA damage measured in lymphocytes was higher in workers from the high temperature and carbon monoxide-exposed groups. We suggest that the increased frequency of antibodies to Hsps is the result of these damages of the release of denatured Hsps and of a decrease in the phagocytic ability of macrophages in these workers. The data gathered in the present study show a statistical relation between the occurrence of antibodies against Hsps and the frequency of health problems in workers and suggest a potential role for the antibodies as useful biomarkers to assess whether workers are experiencing environmental stress.

Effects of dietary supplementation of multi-enzyme on growth performance, nutrient digestibility, small intestinal digestive enzyme activities, and large intestinal selected microbiota in weanling pigs.

Two experiments were conducted to assess the effects of dietary supplementation of an exogenous multi-enzyme (EME) preparation to 35- to 65-d-old piglets on apparent total tract digestibility (ATTD), growth performance, digestive enzyme activities, and selected microbial populations in feces. In Exp.1, twenty eight 35-d-old piglets were randomly assigned to 7 dietary treatments (corn-soybean based diet supplemented with 0, 100, 150, 200, 250, 300, or 350 mg EME/kg) in a 14-d digestibility study. Piglets fed the diets supplemented with EME had greater ATTD of DM, CP, and GE (P = 0.001, 0.005, and 0.009, respectively) than those fed the diet without EME supplementation, and those ATTD values increased linearly and quadratically (P < 0.001) as the levels of supplemented EME increased. In Exp. 2, two hundred 35-d-old weanling piglets were randomly allocated to 20 pens. The pens were then randomly assigned to 5 dietary treatments (corn-soybean based diet supplemented with 0, 100, 150, 250, or 350 mg EME/kg) with 4 pens per treatment in a 30-d feeding experiment. Piglets has ad libitum access to diets and water, and they were weighed at the beginning (35-d-old), middle (50-d-old), and end (65-d-old) of the experiment. Fecal samples were grabbed directly from the rectum and digesta samples from duodenum, jejunum, and ileum were taken at the end of the experiment for the analysis of selected bacteria populations and digestive-enzyme activities. The ADG and ADFI tended to be greater with the increasing levels of supplemented EME in both periods, whereas G:F was improved (P = 0.012 and 0.017) by EME in the period of 35 to 50 d of age and during the overall experimental period. Furthermore, inclusion of EME in diet increased the counts of Lactobacilli spp. and Bacillus subtilis spp., but reduced the populations of Salmonella spp. and Escherichia coli spp. in the feces. The EME supplementation also enhanced (P < 0.05) the activities of amylase, lipase, and protease in the small intestine. The growth performance-enhancing effects of EME appeared to be mediated by the age of the piglet and the dose of EME used. Supplementation of corn-soybean meal diets for 35- to 65-d-old piglets with EME has a potential to enhance gut health condition, increase nutrient digestion, and increase growth performance.

A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt-TSC2-mTOR signaling.

Nanoparticles are now emerging as a novel class of autophagy activators. Functionalized single-walled carbon nanotubes (f-SWCNTs) are valuable nanomaterials in many industries. This article is designed to assess the autophagic response for f-SWCNTs exposure in vitro and in vivo. A few types of f-SWCNTs were screened in human lung adenocarcinoma A549 cells for the autophagic response and related pathways in vitro. Formation of autophagosomes and LC3-II upregulation were confirmed on the basis of electron microscopy and LC3 western blotting for COOH-CNT, but not for PABS-CNT and PEG-CNT. MTT assay showed marked increase in cell viability, when COOH-CNT was added to cells in the presence of autophagy inhibitor 3MA, ATG6 or TSC2 siRNA. Consistent with the involvement of the Akt-TSC1/2-mTOR pathway, the phosphorylation levels of mTOR, mTOR's substrate S6 and Akt were shown significantly decreased in A549 cells on treatment with COOH-CNT using western blotting. What's more, autophagy inhibitor 3MA significantly reduced the lung edema in vivo. In a word, COOH-CNT induced autophagic cell death in A549 cells through the AKT-TSC2-mTOR pathway and caused acute lung injury in vivo. Inhibition of autophagy significantly reduced COOH-CNT-induced autophagic cell death and ameliorated acute lung injury in mice, suggesting a potential remedy to address the growing concerns on the safety of nanomaterials.