OBJECTIVETo study the changes in the expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FP1) in the substantia nigra (SN) of rats with manganese-induced parkinsonism.

METHODSEighty Sprague-Dawley rats were randomly divided into four groups. Rats in the control group were injected intraperitoneally with saline solution. Rats in the low-dose, medium-dose, and high-dose groups were injected intraperitoneally with 5, 15, and 20 mg/kg MnC12 solution, respectively, for 16 weeks. Three behavioral tests were performed at the 16th week. The concentration of Mn2+ in the SN was determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES), and the positive expression of tyrosine hydroxylase (TH) was measured by immunohistochemical staining to determine whether rats with manganese-induced parkinsonism were successfully produced. The expression of DMT1 and FP1 in SN was measured by immunohistochemical staining and fluorescent quantitative polymerase chain reaction.

RESULTSRats with manganese-induced parkinsonism were successfully produced using the above method. Compared with that in the control group, the concentrations of Mn2+ in the SN of rats exposed to 5, 15, and 20 mg/kg Mn2+ were significantly higher (1.72?0.33 vs 0.56 ± 0.20 µg/g, P<0.01; 2.92±0.77 vs 0.56±0.20 µg/g, P<0.01; 5.65±1.60 vs 0.56±0.20 µg/g, P<0.01). The mean ODs of TH-positive cells in the SN of rats exposed to 5, 15, and 20 mg/kg Mn+ were significantly lower than that in the control group (0.054±0.008 vs 0.109±0.019, P<0.01; 0.016±0.004 vs 0.109±0.019, P<0.01; 0.003±0.001 vs 0.109±0.019, P<0.01). Compared with that in the control group, the mean optical densities (ODs) of DMT1-positive cells in the SN of rats exposed to 15, and 20 mg/kg Mn2+ were significantly higher (0.062±0.004 vs 0.015±0.007, P<0.01; 0.116±0.064 vs 0.015±0.007, P<0.01). The mean ODs of FP1-positive cells in the SN of rats exposed to 5, 15, and 20 mg/kg Mn2+ were significantly lower than that in the control group (0.092±0.011 vs 0.306±0.081, P<0.01; 0.048±0.008 vs 0.306±0.081, P<0.01; 0.008±0.002 vs 0.306±0.081, P< 0.01). Rats exposed to 15 and 20 mg/kg Mn2+ had significantly higher expression of DMT1 mRNA in the SN than those in the control group (0.052±0.0126 vs 0.001±0.0004, P<0.05; 0.124±0.0299 vs 0.001±0.0004, P<0.05). However, rats exposed to 5, 15, and 20 mg/kg Mn2 had significantly lower expression of FP1 mRNA in the SN than those in the control group (0.059±0.0076 vs 0.162±0.0463, P<0.05; 0.033±0.0094 vs 0.162±0.0463, P< 0.05; 0.002±0.0007 vs 0.162±0.0463, P<0.05).

CONCLUSIONThe increased expression of DMT1 and reduced expression of FP1 may be involved in the processes of Mn2+ accumulation in the SN and dopaminergic neuron loss in rats with manganese-induced parkinsonism.

Animals ; Cation Transport Proteins ; metabolism ; Disease Models, Animal ; Manganese ; adverse effects ; Parkinsonian Disorders ; chemically induced ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; metabolism ; physiopathology

Objective To study the protection of taurine(TAU) against apoptosis of neurons induced by manganese(Mn) in vitro. Method Cortex neurons were separated from Wistar neonatal rats and cultured in vitro.The assays began when neurons grew under the best conditions. Cells were randomly divided into 7 groups: control group,Mn-added groups (Mn 0.2,0.6 and 1.0 mmol/L respectively),TAU-intervened groups (1.5mmol/L TAU with Mn). All treatments lasted 24h. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was used to observe the morphology of apoptosic neurons. Flow cytometry (FCM) was used to quantitate neuron apoptosic rates. Results (1) Typical morphologic charateristic was found in Mn-added groups. TAU intervention could protect against the effect of 1.5mmol/l Mn on neurons. (2) FCM indicated that TAU can protect against neurons apoptosis induced by Mn. Conclusion Taurine can protect neurons from apoptosis induced by Mn in vitro.

Objective: To investigate the effects of the cooperative actions of isoflavone, vitamin C and E on the expression of acute C reactive protein (CRP) and interleukin 6 (IL-6) in the patients with typeⅡdiabetic mellitus (DM). Method: Ninety six patients with DM were divided randomly into 4 groups, DM control group(B), and groups receiving low(C), medium (D) , and high (E) dose of the compound antioxidant of isoflavone, vitamin C and E respectively. Another 24 healthy subjects served as normal control group (A). Observe the changes of the levels of CRP and IL-6 during oral glucose tolerance test (OGTT). Results: The peak of serum levels of CRP and IL-6 in the patients of DM control group and lower dosage group appeared 1 h after OGTT and were significantly higher than the 0 h value (P

Objective: To observe the co-effect of antioxidant compound, soybean isoflavone (SI), VC and VE on glucose and insulin response after oral glucose load in Type 2 Diabetes Mellitus (T2DM) . Methods: 96 selected T2DM patients (50% male, 50% female) were randomly divided into 4 groups according to the dosage of the compound given , none (group B), low dosage (group C), medium dosage (group D) and high dosage (group E) . The normal control (group A) included 24 persons half male, half female . Blood glucose and insulin were determined at OGTT 0 h, 1 h, 2 h, 4 h, 6 h, and the areas under the curve (AUC) of blood insulin/glucose were calculated. Results: The AUC of blood insulin/glucose of male was higher than female in control group, but both were lower than those of four diabetes groups. In both genders of the diabetes groups, blood insulin AUC of group C, D, E was lower than group B, blood glucose AUC of group D, E was lower than group C and B. There was significant difference in blood insulin and glucose AUC of group E as compared to group B in female (P

Objective: To elucidate the effect of taurine on neurotoxicity induced by Mn by investigating activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase and content of Mn and active calmodulin in manganese exposed rats. Methods: 156 male SD rats were randomly divided into 1 control group, 3 manganese exposed groups (10, 15, and 20 mg/kg respectively) , and 9 taurine intervened groups based on orthogonal design (doses of taurine intervention were 100, 150, and 200 mg/kg respectively) , with 12 rats in each group. After 12 weeks of exposure, all rats were decapitated and corpus striatums were removed, activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase and content of Mn and active calmodulin were analyzed. Results: The corpus striatum Mn content of the 3 dose groups exposed to Mn and 9 taurine intervened groups were significantly higher than that of the control group (P<0.05) . Active calmodulin content in 10 mg/kg manganese exposed group was significantly higher than that of the control group (P<0.05) . 150 and 200 mg/kg of taurine could decrease active calmodulin content of the group exposed to 10 mg/kg of Mn (P<0.05) . The corpus striatum activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase of the 3 dose groups exposed to Mn were significantly lower than that of the control group (P<0.05) . 150 mg/kg of taurine could increase activities of Na⁺-K⁺-ATPase of the group exposed to 10 mg/kg of Mn (P<0.05) . 150 and 200 mg/kg of taurine could respectively improve activities of Ca²⁺-Mg²⁺-ATPase of the group exposed to 15, 10 mg/kg of Mn (P<0.05) . Conclusion Mn can decrease the rats corpus striatum activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase, effect level of active calmodulin in relation to dose of Mn, to a certain extent, taurine could regulate activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase and improve the level of active calmodulin.

Objective: To elucidate the effect of taurine on neurotoxicity induced by Mn by investigating cell cycle and apoptosis in manganese exposed rats. Methods: 156 healthy male SD rats were randomly divided into 1 control group, 3 manganese exposure groups (10, 15, and 20 mg/kg respectively) , and 9 intervened groups based on orthogonal design, with 12 rats in each group. After 12 weeks of exposure, all rats were decapitated and striatums were removed, cell cycle was analyzed by flow cytometry, the apoptosis was detected by TUNEL, level of Mn was determined. Results: The striatum apoptosis index of the 3 dose groups exposed to Mn were significantly higher than control group (P<0.05) . The striatum apoptosis index of the 9 intervened groups were significantly higher than control group (P<0.05) . 150 and 200 mg/kg of taurine could decrease apoptosis index of the group exposed to 10、15、20 mg/kg of Mn (P<0.05) . The striatum Mn content of the 3 dose groups exposed to Mn were significantly higher than that of the control group (P<0.05) . The G0/G1 proportion of the 3 dose groups exposed to Mn were significantly lower than that of the control group (P<0.05) , the S proportion of the 3 dose groups exposed to Mn were significantly higher than that of the control group (P<0.05) . Conclusion Mn could cause cell cycle arrest to S, increase level of apoptosis in striatum, to a certain extent, taurine can protect neurons from apoptosis induced by Mn.

Objective The ammonia level in air and heavy metals in drinking water were explored in a cynomolgus monkey feedlot. Methods Air ammonia from different communities and feeding patterns of cynomolgus monkeys were collected at three time-points per day and determined by Nessler's reagent spectrophotometry. Inductively coupled plasma mass spectrometry was applied to detect the level of heavy metals in drinking water from 5 different sampling sites in the feedlot,incluing the outlet of underground water,the water tank,both monkey cages equipped with PVC or iron pipes and sewage lagoon,respectively. Results Air ammonia levels in quarantine inspection flock cages(0.59 ± 0.03 mg/m3)were significantly higher than in the cages of both reproductive flock(0.34 ± 0.03 mg/m3)and sale flock(0.27 ± 0.04 mg/m3). The ammonia level in air in different feeding patterns ranks as following:cage rearing of quarantine inspection flock(0.59 ± 0.03 mg/m3)>cage rearing of reproductive flock(0.48 ± 0.02 mg/m3)>captive bleeding of sale flock(0.30 ± 0.02 mg/m3)>cage rearing of sale flock(0.25 ± 0.01 mg/m3)> captive bleeding of reproductive flock(0.22 ± 0.02 mg/m3). The air ammonia concentrations of both former flocks were statistically higher than the latter three flocks. The highest air ammonia level among different flocks and feeding patterns occurred in the morning, before waste discharge clean-up. The iron concentration in drinking water in the cages equipped with iron pipes was higher than Chinese drinking water standard. Conclusions The air ammonia level was lower than the Chinese air quality standard. The iron concentration in drinking water in the cages equipped with iron pipes was higher than the Chinese drinking water standard.

ObjectiveTo explore the metabolic changes during the development of Tupaia belangeri breast tumors, to investigate the close relationship between the changes of serum metabolic substances and the occurrence and progression of tumors, and to screen for biomarkers reflecting the progression of breast tumors. MethodsBreast tumors in Tupaia belangeri were induced by orally administering 7,12-dimethylbenzoanthracene (DMBA) three times, with a 15-day interval between each administration, along with a high-fat and high-sugar diet. The DMBA-induced breast cancer group and the DMBA-inducedwithout breast cancer group were compared with the control group. Untargeted determination of serum metabolites was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) in DMBA-induced Tupaia belangeri with breast cancer, DMBA-induced without breast cancer and the control group. Multidimensional statistical analysis including unsupervised principal component analysis (PCA), and orthogonal partial least squares analysis (OPLS-DA) were conducted. Furthermore, t-test was used for intergroup differential comparison. Differential metabolites were screened under VIP>1 and P<0.05 conditions, and significantly changing differential metabolites were identified using the HMDB online database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was utilized to enrich metabolic-related gene regulatory pathways. ResultsThe incidence of breast tumors was 40% in DMBA-induced Tupaia belangeri. Compared with the control group, 30 metabolic differential products were detected in the serum of the group with breast cancer, with 18 down-regulated and 12 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in four metabolic pathways: glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism. Compared with the group without breast cancer, 18 metabolic differential products were detected, with 7 down-regulated and 11 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in the citric acid cycle and glutamate metabolism. Compared with the control group, 31 metabolic differential products were detected in the serum of the groups without breast cancer, with 14 down-regulated and 17 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in three metabolic pathways: glutamate metabolism, glyceride metabolism, and citric acid cycle. ConclusionMetabolomics analysis can reveal the characteristics of changes in metabolites in the serum of breast tumors. The results suggest that glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism pathways are associated with the occurrence and development of DMBA-induced breast tumors in Tupaia belangeri. It provides a foundation for further research into the biological mechanism of breast cancer.