OBJECTIVE: To explore the effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B₁₂ in young SD rats. METHODS: At first, the physical and chemical properties of titanium dioxide nanoparticles, such as particle size, shape, crystal form and agglomeration degree in solution system, were characterized in detail. Eighty 4-week-old young SD rats were randomly divided into 8 groups (10 rats in each group, half male and half female). The rats were exposed to titanium dioxide nanoparticles through intragastric administration at 0, 2, 10 and 50 mg/kg body weight with or without 1.8 g/kg glucose daily for 90 days. At last, the concentrations of serum folate and vitamin B₁₂ were detected. RESULTS: Titanium dioxide nanoparticles were anatase crystals, closely spherical shape, with an average particle size of (24±5) nm. In male young rats, compared with the control group, the serum folate concentration was significantly increased when exposed to titanium dioxide nanoparticles (10 mg/kg) and glucose. The difference was statistically significant (P<0.05). However, in female and male young rats, compared with glucose (1.8 g/kg) exposure group, titanium dioxide nanoparticles (50 mg/kg) and glucose significantly reduced the serum folate concentration. The difference was statistically significant (P<0.05). Through statistical analysis of factorial design and calculation of interaction, obvious antagonistic effect was observed between titanium dioxide nanoparticles and glucose on the serum folate concentration in the young female SD rats. The combined oral exposure of titanium dioxide nanoparticles and glucose had little effect on the concentration of serum vitamin B₁₂ in the young SD rats, with no significant interaction between the two substances. It was only found that titanium dioxide nanoparticles (2 mg/kg) and glucose significantly increased the serum vitamin B₁₂ concentration, compared with glucose (1.8 g/kg) exposure group. The difference was statistically significant (P<0.05). CONCLUSION Subchronic combined oral exposure of titanium dioxide nanoparticles and glucose had an obvious antagonistic effect on serum folate concentrations in young SD rats.
Animals ; Female ; Folic Acid ; Glucose ; Male ; Metal Nanoparticles ; Rats ; Rats, Sprague-Dawley ; Titanium ; Vitamin B 12 ; Vitamins

OBJECTIVE: To explore the effects and related mechanisms of oral exposure titanium dioxide nanoparticles (TiO₂ NPs) for 90 days on the intestinal and the gut microbiota of rats, through fecal metabolomics. METHODS: Twelve 4-week-old clean-grade Sprague Dawley (SD) rats were randomly de-vided into 2 groups by body weight, treated with TiO₂ NPs at dose of 0 or 50 mg/kg body weight everyday respectively for 90 days. The solution of each infection was freshly prepared and shocked fully by ultrasonic. Characterization of the particle size, crystal form, purity, and specific surface area of TiO₂ NPs was conducted. And the fresh feces of the rats were collected on the 90th day. After lyophilized and hydrophilic phase extraction, ultra performance liquid chromatography-Q-exactive orbitrap-high-resolution mass spectrometry system (UPLC-QEMS) was utilized for non-targeted determination of fecal meta-bolites. The metabolites were identified and labeled through Compound Discoverer 3.0 software, and used for subsequent metabolomics analysis. Bioinformatics analysis was carried out including unsupervised principal component analysis and supervised orthogonal projection to latent structure discriminant analysis for the differential metabolites between the two groups. The differential metabolites were followed-up for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: Compared with the control group, the body weight of the rats was significantly reduced (P<0.05) in the treatment group. A total of 22 metabolites in fecal metabolomics showed significant changes. Among them, xanthine, 1-methyladenine, 3-hydroxypyridine, methionine sulfoxide, pyridoxine, 1,5-isoquinolinediol, N-acetylornithine, N-acetyl-D-galactosamine, L-citrulline, L-methionine, leucine, DL-tryptophan, L-ornithine, 4-methyl-5-thiazoleethanol, and L-glutamic acid totaled 15 metabolites increased significantly. N-acetylhistamine, D-pipecolinic acid, imidazolelactic acid, L-valine, 2,3,4,6-tetramethylpyrazine, caprolactam, and histamine totaled 7 metabolites decreased significantly. N-acetylhistamine, L-valine and methionine sulfoxide were changed more than 16 times. Analysis of KEGG pathway revealed that the two metabolic pathways arginine biosynthesis and aminoacyl-tRNA biosynthesis were significantly changed (false discover rate < 0.05, pathway impact > 0.1). CONCLUSION Oral exposure to TiO₂ NPs for 90 days could disrupt the metabolism of the intestine and gut microbiota, causing significant changes in metabolites and metabolic pathways which were related to inflammatory response, oxidative stress, glucose homeostasis, blood system and amino acid homeostasis in rat feces. It is suggested that the toxic effect of TiO₂ NPs on rats may be closely related to intestinal and gut microbiota metabolism.
Administration, Oral ; Animals ; Feces ; Metabolome ; Metal Nanoparticles ; Rats ; Rats, Sprague-Dawley ; Titanium

Objective:To evaluate the effects of exposure of fine particle matter (PM 2.5) and ozone (O 3) in Beijing as the main pollutants on olfaction of SD rats. Methods:In October 16, 2018, twenty 8-week-old SD rats were randomly divided into two groups, 10 rats in the exposure group and 10 rats in the control group. They were fed in air pollutant exposure system and clean experimental environment respectively, and the concentrations of PM 2.5 and O 3 in each system were measured. The degree of olfaction damage of SD rats at different feeding time was assessed by using the buried food test (BFT). The difference of BFT time between the two groups was analyzed by performing the repeated measures analysis of variance. Results:The results showed that the concentrations of PM 2.5 and O 3 in the exposure group were (22.65±11.47) μg/m 3 and (12.36±5.87) μg/m 3, respectively, while those in the control group were both 0 μg/m 3. The repeated measures analysis of variance showed that the time of BFT in the exposure group was longer than that in the control group ( F=6.49, P=0.031). With the increase of feeding time, the time of BFT was prolonged ( F=61.69, P<0.001). Conclusion:Exposure to PM 2.5 and O 3in the atmosphere might lead to olfaction damage in rats.

Objective:To evaluate the effects of exposure of fine particle matter (PM 2.5) and ozone (O 3) in Beijing as the main pollutants on olfaction of SD rats. Methods:In October 16, 2018, twenty 8-week-old SD rats were randomly divided into two groups, 10 rats in the exposure group and 10 rats in the control group. They were fed in air pollutant exposure system and clean experimental environment respectively, and the concentrations of PM 2.5 and O 3 in each system were measured. The degree of olfaction damage of SD rats at different feeding time was assessed by using the buried food test (BFT). The difference of BFT time between the two groups was analyzed by performing the repeated measures analysis of variance. Results:The results showed that the concentrations of PM 2.5 and O 3 in the exposure group were (22.65±11.47) μg/m 3 and (12.36±5.87) μg/m 3, respectively, while those in the control group were both 0 μg/m 3. The repeated measures analysis of variance showed that the time of BFT in the exposure group was longer than that in the control group ( F=6.49, P=0.031). With the increase of feeding time, the time of BFT was prolonged ( F=61.69, P<0.001). Conclusion:Exposure to PM 2.5 and O 3in the atmosphere might lead to olfaction damage in rats.

Objective: To study the mRNA expressions of various CD97 isoforms in colorectal carcinoma tissues and their clinical significances. Methods: A total of 50 colon cancer patients in the First Affiliated Hospital of Wenzhou Medical University from December 2013 to May 2014 and human colon cancer cell lines SW480 and SW620 were enrolled. The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expressions of CD97 human epidermal growth factor (EGF) (1, 2, 5), CD97EGF (1, 2, 3, 5) and CD97EGF (1, 2, 3, 4, 5) in colon cancer tissues, adjacent tissues, normal colon tissues, SW480 cells and SW620 cells. The relationship between the mRNA expression of CD97EGF (1, 2, 5) and the clinicopathological factors was analyzed. Results: Compared with those low expressions in adjacent tissues and normal tissues, the mRNA expressions of CD97 isoforms CD97EGF (1, 2, 5), CD97EGF (1, 2, 3, 5) and CD97EGF (1, 2, 3, 4, 5) in cancer tissues were highest, and the differences were statistically significant (0.71±0.20 vs. 0.40±0.09 vs. 0.35±0.07, F = 107.642, P < 0.01; 0.45±0.11 vs. 0.26±0.05 vs. 0.27±0.06, F = 94.231, P < 0.01; 0.41±0.10 vs. 0.21±0.05 vs. 0.19±0.03, F = 165.672, P < 0.01). In addition, the mRNA expression of CD97EGF (1, 2, 5) in colon cancer patients was associated with tumor infiltration depth (T₁-T₂ and T₃-T₄), clinical stages (Ⅰ-Ⅱ and Ⅲ-Ⅳ), and the differences were statistically significant (t = -2.582, P = 0.013; t = -5.062, P < 0.01). The mRNA expression of CD97EGF (1, 2, 5) in SW620 cells was higher than that in SW480 cells. Conclusions CD97 isoforms are highly expressed in colon cancer tissues, and CD97EGF (1, 2, 5) may play an important role in the development and invasion of colon cancer. The CD97 isoforms may be new markers in the treatment of colon cancer.

Objective To study whether ferulic acid can promote healing on chronic ischemic wounds and its possible mechanisms.Methods 40 male New Zealand white rabbits were randomly divided into 4 groups:vaseline group,ischemic control group,5％ ferulic acid group and recombinant bovine basic fibroblast growth factor for external use (rb-bFGF) group.Gross wounds were carefully observed and HE staining was used to observe the wound healing and immumohistochemical staining to observe the expression of the VEGF and CD31.The RNA was extracted to detect the expression of VEGF and HIF-1a by real-time PCR.Results The general observation and the HE staining of each specimen 11 days after operation all indicated that the duration of wound healing of the 5 ％ ferulic acid group was similar to that of the rb-bFGF group and markedly shorter than the ischemic control group and the vaseline smear group.The result of the immunohistochemical staining indicated that the content of the VEGF and CD31 expression of the 5 ％ ferulic acid groups and the rb-bFGF group made lit tle difference,but there was markedly less VEGF and CD31 in ischemic control group and the vaseline smear group.The result of the PCR showed that expression level of VEGF and HIF-1α in the 5 ％ fer ulic acid group was similar to that in the rb bFGF group and the vaseline smear group,but was obviously more than that of the ischemic control group and the vaseline smear group (P ＜ 0.05).Conclusions Ferulic acid can promote angiogenesis by increasing VEGF and HIF-1α which are closely related to angiogenesis and then promote the healing of chronic wounds.

Aged ; Female ; Humans ; Myocardial Infarction ; diagnosis ; Polycythemia Vera ; complications