Chronic low-dose exposure of nonylphenol alters energy homeostasis in the reproductive system of female rats.

Nonylphenol (NP) as a confirmed endocrine disrupt chemical that causes reproductive and developmental toxicity. Previous studies focused only on short-term, high-dose exposure in vivo, or in vitro on female reproductive toxicity, which cannot accurately simulate the real human exposure scenario. The present study aims to explore NP toxicity and the underlying mechanisms of chronic low-dose NP exposure (500 µg/kg·bw/day, for 8 weeks) in the reproductive system of female rats. The results indicated that NP exposure caused female reproductive toxicity, including alterations in serum 17ß-estradiol (E2) levels, endometria hyperplasia, altered oogenesis and significant changes in the metabolic profile observed in urine, serum, uterus and ovary. Furthermore, expression of the energy-sensitive proteins carnitine palmitoyltransferase I (CPTI), adenosine 5'-monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma (PPAR-γ) were found to be down-regulated in uterus under NP exposure, which suggested the impaired fatty acid oxidation. Accordingly, a comprehensive metabolomics study in key reproductive tissues and body fluids revealed that 12 metabolites were associated with energy metabolism as potential biomarkers for the evaluation of low toxicity at early stages, with L-carnitines being the most representative ones. The present findings provide evidence that chronic low-dose NP exposure can significantly disrupt energy homeostasis in females, thus offering further insights into NP reproductive toxicity.

[Effect of enteral nutrition on liver function and inflammatory response after abdominal operation in patients complicated with liver dysfunction].

OBJECTIVE: To investigate the effect of enteral nutrition(EN) on liver function and inflammatory response after abdominal operation in patients with liver dysfunction. METHODS: A prospective multicenter study was conducted. Patients requiring EN for at least 5 days after abdominal surgery with at least 1 abnormal liver function index were included. After operations, EN suspensions(TPF-FOS) were administered for 5 days after the return of bowel function with targeted content of 125.52 kJ(30 kcal)·kg(-1)·d(-1) maintained for a minimum of 3 days. Levels of serum pre-albumin, C-reaction protein(CRP), and liver function index were measured and the incidence of systemic inflammatory response syndrome(SIRS) was recorded before operation and 6 days after EN. Occurrence of gastrointestinal discomfort was monitored during the treatment. RESULTS: No statistically significant difference was found in pre-albumin between preoperative level and post-EN level[(175.94±71.79) mg/L vs.(192.22±91.26) mg/L, P=0.162]. Patients with abnormal level of γ-glutamyl transpeptidase were less after EN compared to the preoperative period(30 vs. 40, P=0.041), as was total bilirubin (3 vs. 9, P=0.034). No significant differences in other indices of liver function were found. Total bilirubin and direct bilirubin decreased after EN support(P=0.000 and P=0.015, respectively). CRP was notably reduced after EN support [(48.74±65.16) mg/L vs.(25.79±23.63) mg/L, P=0.009] and the incidence of SIRS largely declined after EN support(19.0% vs. 10.3%, P=0.059). The incidence of gastrointestinal discomfort was 22.4% on postoperative day 1 and declined to 19.0% on postoperative day 5. CONCLUSION: For patients with liver dysfunction, enteral nutrition support with TPF-FOS after abdominal operation can reduce inflammatory response, improve liver function, and maintain serum protein level.

Clinical application of subjective global assessment in Chinese patients with gastrointestinal cancer.

AIM: To investigate the role of subjective global assessment (SGA) in nutritional assessment and outcome prediction of Chinese patients with gastrointestinal cancer. METHODS: A total of 751 patients diagnosed with gastrointestinal cancer between August 2004 and August 2006 were enrolled in this study. Within 72 h after admission, SGA, anthropometric parameters, and laboratory tests were used to assess the nutritional status of each patient. The outcome variables including hospital stay, complications, and in-hospital medical expenditure were also obtained. RESULTS: Based on the results of SGA, 389 (51.8%), 332 (44.2%), and 30 (4.0%) patients were classified into well nourished group (SGA-A), mildly to moderately malnourished group (SGA-B), and severely malnourished group (SGA-C), respectively. The prevalence of malnutrition classified by SGA, triceps skinfold thickness (TSF), mid-upper arm muscle circumference (MAMC), albumin (ALB), prealbumin (PA), and body mass index (BMI) was 48.2%, 39.4%, 37.7%, 31.3%, 21.7%, and 9.6%, respectively. In addition, ANOVA tests revealed significant differences in body mass index (BMI), TSF, PA, and ALB of patients in different SGA groups. The more severely malnourished the patient was, the lower the levels of BMI, TSF, PA, and ALB were (P < 0.05). Chi2 tests showed a significant difference in SGA classification between patients receiving different types of treatment (surgery vs chemotherapy/radiotherapy). As the nutritional status classified by SGA deteriorated, the patients stayed longer in hospital and their medical expenditures increased significantly. Furthermore, multiple regression analysis showed that SGA and serum ALB could help predict the medical expenditures and hospital stay of patients undergoing surgery. The occurrence of complications increased in parallel with the increasing grade of SGA, and was the highest in the SGA-C group (23.3%) and the lowest in the SGA-A group (16.8%). CONCLUSION: SGA is a reliable assessment tool and helps to predict the hospital stay and medical expenditures of Chinese surgical gastrointestinal cancer patients.

[Reappraisal of the impacts of human Runt-related transcription factor gene 3 expression on differentiation and prognosis of gastric cancer].

OBJECTIVE: To investigate the expression of Runt-related transcription factor gene 3(RUNX3) in gastric cancer and its impact on the outcome of gastric cancer patients. METHODS: By using immunohistochemistry staining and western blot assay, the expression of RUNX3 protein in 66 cases of gastric cancer with various clinicopathologic characteristics were detected, and the effects of RUNX3 protein expression on the outcome of patients undergone surgical resection were evaluated. RESULTS: (1) The expression rate of RUNX3 protein in gastric cancer lesions was 60.6% (40/66), and RUNX3 protein was mainly expressed in the cytoplasm of cancer cells. RUNX3 protein expression in tumor tissues was significantly higher than that in non-tumor tissues. (2) RUNX3 protein expression was correlated with tumor differentiation (P=0.025) and Lauren's classification (P=0.034), but had no relationship with the TNM stage (P=0.085). (3) In sharp contrast, the median survival time of patients who had tumors with negative and positive RUNX3 protein expression were 2478 and 2187 days respectively (P=0.016). CONCLUSIONS: RUNX3 protein influences the differentiation of gastric cancer. The role of RUNX3 protein as a tumor-suppressor in tumorigenesis and differentiation of gastric carcinoma need to be further evaluated.

Applying proteomic methodologies to analyze the effect of methionine restriction on proliferation of human gastric cancer SGC7901 cells.

BACKGROUND: Methionine dependence is a feature unique to cancer cells, exhibited as inability to grow in a methionine-depleted environment supplemented with homocysteine, the immediate metabolic precursor of methionine. However, the molecular mechanisms by which methionine restriction inhibits cancer cells growth have not been elucidated. The effect of methionine restriction on the protein expression in gastric cancer cells was studied. METHODS: SGC7901 cells were treated with M-H+ medium for 5 days, which was followed by analysis of total cellular protein from cells by a combination of 2-DE and MS. Then the differential expressional levels of partially identified proteins were determined by Western blot analysis. RESULTS: The well-resolved, reproducible 2-DE patterns of SGC7901 cells cultured in M+H- or M-H+ medium were established. The 10 differential proteins between pairs of gastric cancer cells SGC7901 cultured either in M+H- medium or M-H+ medium, were identified by MALDI-TOF/TOF MS, and the differential expression levels of 2 identified proteins were confirmed. CONCLUSION: These data will be valuable for further study of the molecular mechanisms by which methionine restriction induces cell cycle arrest and apoptosis in human gastric cancer.

[Immunotherapeutic efficacy of both helper T lymphocytes and cytotoxic T lymphocytes epitopes augmented dendritic cells tumor vaccine on gastric cancer].

OBJECTIVE: To investigate the immunotherapy efficacy of both helper T lymphocytes (Th) and cytotoxic T lymphocytes (CTL) epitopes augmented dendritic cells (DCs) tumor vaccine on gastric cancer. METHODS: Naïve spleen T cells were stimulated by mixed peptides (a mixture of Th epitope MAGE-3 (22-36)) primed DCs per week in vitro. After 4 cycles of restimulation, peptide specific T cells were harvested and subgroups of which were determined with flow cytometry. Cytokines secreting profiles by CD4+ T cells and cytotoxicities of CD8+ T cells on tumor cells were assessed. The protective immunity by referred DCs tumor vaccines was also monitored. RESULTS: Both Th and CTL epitopes primed DCs could elicit both CD4+ T cells and CD8+ T cells in vitro,of which CD4+ T cells released high amount of Th1 type cytokines (IFN-gamma, IL-2) on recognizing specific antigen, as well as CD8+ T cells exhibited efficient tumor-killing capacity. The effects induced by DCs pulsed with single epitope (Th or CTL epitope) in vivo were less effective than those induced by DCs pulsed with mixture epitopes. CONCLUSIONS: Both Th and CTL epitopes augmented DCs tumor vaccine can induce CD4+ Th1 and CD8+ CTL mediated immune responses to eradicate gastric cancer cells.

Methionine-dependence and combination chemotherapy on human gastric cancer cells in vitro.

AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial cells in vitro can grow normally in a methionine (Met) depleted environment, i.e. Met-dependence, and whether Met-depleting status can enhance the killing effect of chemotherapy on gastric cancer cells. METHODS: Fresh human gastric cancer and mucosal tissues were managed to form monocellular suspensions, which were then cultured in the Met-free but homocysteine-containing (Met(-)Hcy(+)) medium, with different chemotherapeutic drugs. The proliferation of the cells was examined by cell counter, flow cytometry (FCM) and microcytotoxicity assay (MTT). RESULTS: The growth of human primary gastric cancer cells in Met(-)Hcy(+) was suppressed, manifested by the decrease of total cell counts [1.46 +/- 0.42 (x 10(9).L(-1)) in Met(-)Hcy(+) vs 1.64 +/-0.44(x 10(9).L(-1)) in Met(+)Hcy(-), P<0.01], the decline in the percentage of G(0)G(1) phase cells (0.69 +/- 0.24 in Met(-)Hcy(+) vs 0.80 +/- 0.18 in Met(+)Hcy(-), P<0.01) and the increase of S cells (0.24 +/- 0.20 in Met(-)Hcy(+) vs 0.17 +/- 0.16 in Met(+)Hcy(-), P<0.01); however, gastric mucosal cells grew normally. If Met(-)Hcy(+) medium was used in combination with chemotherapeutic drugs, the number of surviving gastric cancer cells dropped significantly. CONCLUSION: Human primary gastric cancer cells in vitro are Met-dependent; however, gastric mucosal cells have not shown the same characteristics. Met(-)Hcy(+) environment may strengthen the killing effect of chemotherapy on human primary gastric cancer cells.

A study of preoperative methionine-depleting parenteral nutrition plus chemotherapy in gastric cancer patients.

AIM:To investigate the interference of methionine-free parenteral nutrition plus 5-Fu (-MetTPN+5-Fu) in gastric cancer cell kinetics and the side effects of the regimen.METHODS:Fifteen patients with advanced gastric cancer were randomly divided intotwo groups, 7 patients were given preoperatively a seven-day course of standard parenteral nutrition in combination with a five-day course of chemotherapy (sTPN+5-Fu), while the other 8 patients were given methionine-deprived parenteral nutrition and 5-Fu (-MetTPN+5-Fu). Cell cycles of gastric cancer and normal mucosa were studied by flow cytometry (FCM). Blood samples were taken to measure the serum protein, methionine (Met) and cysteine (Cys) levels, and liver and kidney functions.RESULTS:As compared with the results obtained before the treatment, the percentage of G(0)/G(1) tumor cells increased and that of S phase decreased in the -MetTPN+5-Fu group, while the contrary was observed in the sTPN+5-Fu group. Except that the ALT, AST and AKP levels were slightly increased in a few cases receiving -MetTPN+5-Fu, all the other biochemical parameters were within normal limits. Serum Cys level decreased slightly after the treatment in both groups. Serum Met level of patients receiving sTPN+5-Fu was somewhat higher after treatment than that before treatment; however, no significant change occurred in the -MetTPN+5-Fu group, nor operative complications in both groups.CONCLUSION:-MetTPN+5-Fu exerted a suppressive effect on cancer cell proliferation, probably through a double mechanism of creating a state of "Met starvation" adverse to the tumor cell cycle, and by allowing 5-Fu to kill specifically cells in S phase. Preoperative shortterm administration of -MetTPN+5-Fu had little undesirable effect on host metabolism.