Subchronic Toxicity of GmDREB3 Gene Modified Wheat in the Third Generation Wistar Rats.

The aim of the current study was to evaluate the subchronic toxicity of GmDREB3 gene modified wheat in the third generation rats. SPF Wistar rats were fed with transgenic wheat diet (Gm), parental wheat diet (Jimai22) and AIN-93 rodent diet (Control), respectively, for two generations, to produce the third generation rats which were used for this study. The selected fresh weaned offspring rats (20/sex/group) were given the same diet as their parents for 13 weeks. No toxicity-related changes were observed in rats fed with Gm diet in the following respects: clinical signs, body weights, body weight gains, food consumption, food utilization rate, urinalysis, hematology, serum biochemistry and histopathology. The results from the present study demonstrated that 13 weeks consumption of Gm wheat did not cause any adverse effects in the third generation rats when compared with the corresponding Jimai22 wheat.

Cancer-Associated Fibroblasts Correlate with Tumor-Associated Macrophages Infiltration and Lymphatic Metastasis in Triple Negative Breast Cancer Patients.

Background: Cancer-associated fibroblasts (CAFs) have been shown to be among the most prominent cells in tumor microenvironment and play a significant role in accelerating tumor metastasis by interacting with other type of cells. Tumor-associated macrophages (TAMs), the predominant tumor-infiltrating immune cells, also play important roles in cancer progression. Here, we aimed to evaluate the effects of CAFs on infiltration of TAMs and lymphatic metastasis in triple-negative breast cancer (TNBC). Material and methods: The study included 278 patients with histologically confirmed TNBC. Immunohistochemical staining of α-smooth muscle actin and fibroblast activation protein were used to identify CAFs. Polarized functional status of infiltrated TAMs was detected by expression of CD163. The clinicopathological features were assessed from all the patients' medical records. Results: The CAFs-related markers were found to be expressed more frequently in TNBC patents with aggressive behaviors, including recurrence and poor histological differentiation. High activation of CAFs was positively correlated with elevated infiltration of polarized CD163-positive TAMs and lymph node metastasis in TNBC patients. Multivariate Cox analysis revealed that the activation of CAFs, TAMs infiltration, and lymph node metastasis were independent prognostic factors for disease-free survival in TNBC patients. Conclusion: Cancer-associated fibroblasts were associated with infiltration of CD163-positive macrophages and lymphatic metastasis, and may be potential prognostic predictors of TNBC.

Inhibition of GABA shunt enzymes' activity by 4-hydroxybenzaldehyde derivatives.

4-Hydroxybenzaldehyde (HBA) derivatives were examined as inhibitors for GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). Investigation of structure-activity relation revealed that a carbonyl group or an amino group as well as a hydroxy group at the para position of the benzene ring are important for both enzymes' inhibition. HBA was shown to give competitive inhibition of GABA-T with respect to alpha-ketoglutarate and competitive inhibition of SSADH. 4-Hydroxybenzylamine (HBM) also showed the competitive inhibition on GABA-T with respect to GABA. In conclusion, the inhibitory effects of HBA and HBM on both enzymes could result from the similarity between both molecules and the two enzymes' substrates in structure, as well as the conjugative effect of the benzene ring. This suggested that the presence of the benzene ring may be accepted by the active site of both enzymes, HBA and HBM may be considered as lead compounds to design novel GABA-T inhibitors.

[Enhanced absorption of breviscapine photosomes in small intestine of rats].

OBJECTIVE: To investigate whether the absorption of breviscapine can be enhanced by using breviscapine photosomes. METHOD: Testing the uptake and intestinal permeability of breviscapine powder and breviscapine photosomes by using intestine perfusion technique and reverted gut sac method. RESULT: The uptake and permeability coefficient of breviscapine were increased in photosomes. The absorption process obeyed the Fick's law in the range of 0-100 microg x mL(-1). CONCLUSION: The absorption breviscapine photosomes is enhanced by increasing the permeability through a passive mechanism.

Protective effects of scutellarin on superoxide-induced oxidative stress in rat cortical synaptosomes.

AIM: To evaluate the effects of scutellarin on superoxide-induced oxidative stress in rat cortical synaptosomes. METHODS: Oxidative damage model was established by incubation with xanthine (0.3 mmol/L) and xanthine oxidase (0.02 U) at 37 degree for 30 min. The extent of membrane oxidation was assessed by malondialdehyde (MDA). Membrane fluidity was measured by fluorescence anisotropy (polarization) of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Intracellular Ca2+ concentration([Ca2+]i) was measured by fluorescent spectrophotometry. Fura 2-AM was used as an indicator for [Ca2+]i. Na+/K+-ATPase activity assay was based on the amount of inorganic phosphate (Pi) released during an enzymatic hydrolysis of ATP. RESULTS: Synaptosomes exposed to superoxide significantly elevated the levels of malondialdehyde (MDA) and [Ca2+]i compared with those in normal group. These changes were accompanied by the decrease in membrane fluidity and Na+/K+-ATPase activity. Pretreatment with scutellarin (25-100 micromol/L) significantly ameliorated the oxidative damage of synaptosomes by reducing MDA levels and [Ca2+]i, up-regulating membrane fluidity and restoring Na+/K+-ATPase activity. CONCLUSION: Scutellarin exerts a potent protective effect against oxidative damage in synaptosomes induced by superoxide.