Effects of atmospheric particulates exposure on Nrf2 signaling pathway and inflammatory factors in myocardium of rats fed with high-fat and high-glucose diet / 上海预防医学

Objective To study the effect of atmospheric particulate exposure on the expression of key molecules of Nrf2 signaling pathway involved in oxidative stress and inflammatory response factors in myocardium of rats fed with high-fat and high-glucose diet. Methods A total of 48 SD male rats were randomly divided into control group (CC group), high-fat and high-glucose diet group (HC group), atmospheric particulates group (CP group) and atmospheric particulates plus high-fat and high-glucose diet group (HP group), with 12 rats in each group.Rats were fed in individual ventilated cages (IVC).The CC and HC groups were placed in IVCs equipped with the atmospheric particulate filter, however, the CP and HP groups without the atmospheric particulate filter to make the air composition similar to the outdoor.A total of 24 rats were sacrificed for acquiring myocardial tissue after 3 and 6 months of exposure.The mRNA expression of Nrf2, HO-1, NQO1, VCAM-1 and MCP-1 were measured using RT-qPCR and the protein expression of VCAM-1, MCP-1 detected using western blot. Results The mRNA expression levels of Nrf2, HO-1, NQO1, VCAM-1 and MCP-1 and the protein expression levels of VCAM-1 and MCP-1 in HC, CP and HP groups were higher than CC group (P < 0.05).The mRNA expression levels of Nrf2, HO-1, NQO1, VCAM-1, MCP-1 and the protein expression levels of VCAM-1, MCP-1 in the HP group were higher than HC and CP groups (P < 0.05).The mRNA expression levels of Nrf2 in CP and HP groups after 6 months of exposure were lower than that at 3 months (P < 0.05). Conclusion The exposure of atmospheric particles, high-fat and high-glucose and their combination diets could cause myocardial tissue inflammatory responses, and activate Nrf2 signaling pathways to protect against myocardial damage.

Expression of CD269 and CD317 in Multiple Myeloma and Its Clinical Significance / 现代检验医学杂志

Objective To study the expression of CD269 and CD317 antigens in bone marrow cells of patients with multiple myeloma (MM),analyze its correlation with the laboratory indexes reflecting the progression of MM and evaluate its value in clinical diagnosis and treatment.Methods 63 newly diagnosed MM patients were selected as the study group by a casecontrol study.The expression rate of CD269 and CD317 in bone marrow blood of 35 patients with iron deficiency anemia and other antigens in bone marrow blood of 63 patients with MM were detected by flow cytometry.The levels of serum hemoglo bin (Hb),serumβ2-MG(β2-MG) and lactatedehydrogenase (LDH) in patients with MM were dctectcd,and the levels of CD269 and CD317 were analyzed statistically.Results The positive rates of CD269 in the study group and control group were (86.6±2.35)％ vs (4.33±l.69)％,rcspectivcly (t =4.256,P＜0.05)).The positive rate of CD317 was (71.42+ 0.62)％ vs (8.32+ 3.89)％,the difference was statistically significant (t=3.102,P＜0.05).In other expression,the expression level of CD269 and CD317 in CD56 positive group was significantly higher than that of negative group (t=4.032,P＜0.05),while the expression of CD117 the level of positive group was significantly lower than that of the negative group (t 2.832,P＜0.05),CD19,CD20 expression was not statistically significant difference between the two groups (P＞ 0.05).The levels of CD269 and CD317 in patients with MM were positively correlated with the level of CD56 expression (r =0.392,P＜0.05),and negatively correlated with the level of CD117 expression (r=-0.210,P＜0.05).The levels of CD269 and CD317 in patients with MM were significantly lower than those in the negative group (t=3.012,P＜0.05) and the levels of serum LDH in the positive group were lower than those in the negative group (t=2.024,P＜0.05).There was a negative correlation between Hb content (r=-0.212,P＜0.05) and negatively correlated with serum β2-MG (r=-0.312,P＜0.05).Conclusion The high expression of CD269 and CD317 in bone marrow cells in MM patients is related to the increase of CD56 and decrease of CD117 in patients with MM.

Role of copper transporter protein in copper accumulation in C6 cells induced by lead exposure / 中国职业医学

OBJECTIVE: To investigate the role of copper transporter protein and copper chaperones in copper accumulation in glioma cell line C6 cells induced by lead acetate exposure. METHODS: i) CCK-8 assay was used to determine the proper lead acetate dose by treating the cells with lead acetate at the final concentration of 0-50 μmol / L for 24. 0 hours. ii) C6 cells were divided into control group and lead-exposure group,treated with 0 and 10 μmol / L lead acetate respectively for24. 0 hours,and then cultured in 2 μmol / L copper chloride for 0. 0,0. 5,1. 0,2. 0,4. 0 and 8. 0 hours; inductively coupled plasma mass spectrometry was used to detect the levels of copper and lead in the cells. Real-time polymerase chain reaction was used to detect the mRNA expression of copper transporter 1( CTR1),divalent metal transporter 1( DMT1),copper-transporting ATPase α polypeptide / β polypeptide( ATP7 A and ATP7B), antioxidant 1 copper chaperone( ATOX1),cytochrome c oxidase copper chaperone( COX17),and copper-chaperone-for-superoxide dismutase( CCS).Laser con-focal microscopy was applied to detect the protein expression of CTR1 and ATP7 A in cells. RESULTS: i) CCK-8assay proved that the 10 μmol / L lead acetate treatment did not affect C6 cells proliferation( P > 0. 05). Thus the final concentration of 10 μmol / L lead acetate was chosen as the treatment dose in later experiments. ii) After 10 μmol / L lead acetate exposure for 24. 0 hours,the lead and copper levels of C6 cells in lead-exposure group were higher than those in the control group( P < 0. 01),but there was no statistical significant difference in the C6 cell survival rate between these two groups( P > 0. 05). After cells were treated with copper,the C6 cell survival rate of lead-exposure group was lower than that in the control group( P < 0. 01). The interactive effect of copper level showed statistical significance between lead exposure and cooper treatment time( P < 0. 01). At the 5 time points from 0. 5-8. 0 hours after exposure to copper,the copper levels in lead-exposure group were higher than those of control group( P < 0. 05). The copper levels in the control group reached a peak after exposure to copper for 2. 0 hours,and maintained at a stable level till the time point of 8. 0hours. The copper levels of lead-exposed groups increased with the increasing time of copper exposure and there was a time-effect relationship,and they reached to the peak at the time point of 8. 0 hours. After 10 μmol / L lead acetate exposure for 24. 0 hours,compared with control group,the CTR1 and DMT1 mRNA relative expression levels in leadexposed group increased by 113. 00% and 36. 00% respectively( P < 0. 01),and the ATP7 A mRNA relative expression level decreased by 25. 00%( P < 0. 01). The protein expression of CTR1 increased by 76. 04%( P < 0. 01),and the protein expression of ATP7 A decreased by 16. 0%( P < 0. 01). There was no significant difference in the mRNA relative expression levels of ATP7 B,ATOX1,COX17 and CCS between the two groups( P > 0. 05). CONCLUSION: Lead acetate exposure can lead to increase accumulation of copper in C6 cells with increasing exposure time showing a time-effect relationship. The increased protein expression of CTR1 and decreased protein expression of ATP7 A might be one of the mechanisms of inducing copper accumulation in cells after the lead acetate exposure.

Effect of automotive paint volatile on learning and memory ability and amino acid neurotransmitters in brain tissue of mice / 中国职业医学

OBJECTIVE: To explore the effect of automotive paint volatile on the learning and memory ability and its influence mechanism of the amino acid neurotransmitters in the brain tissue of mice. METHODS: Thirty specific pathogen free healthy male Kunming mice were randomly divided into control group,primer group and topcoat group,10 mice in each group. By static inhalation intoxication method,the primer group and topcoat group were exposed to corresponding paint volatile 600 and 580 mg / m3 respectively every day for 4 weeks,6 days per week,one time a day,2 hours each time.The mice of the control group were kept in the exposure cabinet without any paint volatile. After the exposure,the neuroethology examination was carried out by Morris water maze test. The amino acid levels of glutamic acid( GLU),aspartic acid( ASP),γ-aminobutyric acid( GABA) and glycine( GLY) in brain tissue of mice were detected by high performance liquid chromatography. RESULTS: Compared with the control group,the escape latency and the first crossing platform time were longer( P < 0. 05),target quadrant staying time and platform crossing times were decreased( P <0. 05),and the levels of GLU,ASP,GABA and GLY in brain tissues were decreased in the primer group and the topcoat group( P < 0. 05). There was no significant difference between the primer group and the topcoat group in the above indexes( P > 0. 05). CONCLUSION: Automotive paint volatiles exposure may lower the learning and memory abilities of mice,and could reduce the secretion of amino acid neurotransmitters in the brain tissue of mice.

Expression of Peroxiredoxins and Pulmonary Surfactant Protein A Induced by Silica in Rat Lung Tissue / 生物医学与环境科学（英文）

Silicosis is one of the most serious occupational diseases in China and dates back to centuries ago. In this study, we successfully established a rat model of silicosis by intratracheal silica injection for 28 days and determined hydroxyproline levels to evaluate collagen metabolism in lung homogenates. Oxidative stress status was evaluated by detecting catalase and glutathione peroxidase activities. Expression levels of peroxiredoxins (Prx I and Prx VI) were detected by Western blotting. Pulmonary surfactant protein A (SP-A) levels in rat serum and lung tissue were analyzed by ELISA, and SP-A and Prx expression levels in lung tissues were detected by immunohistochemistry. The results suggest that Prx proteins may be involved in pulmonary fibrosis induced by silica. Downregulation of SP-A expression caused due to silica is an important factor in the occurrence and development of silicosis.

Effect of Decitabine on Megakaryocyte Culture of Steroid-resistant ITP Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of decitabine and plasma of ITP patients on in vitro cultrue of megakaryocytes in bone marrow of steroid-resistant ITP patients.</p><p><b>METHODS</b>Bone marrow mononuclear cells were isolated from 20 steroid-resistant ITP patients, both methyl cellulose semisolid culture system (to observe and count the number of megakaryocytes colony-forming unit) and liquid culture system (to analysis the expression rate of CD41a(+) cells) were used for megakaryocyte cultrue. The experiments were divided into 4 groups according to the different components of the culture system, group A was control, group B was added with decitabine, group C with ITP plasma, group D with both decitabine and ITP plasma, and the rest of the culture components were the same in the 4 groups except the above-mentioned materials. Morphology of megakaryocytes was observed by inverted and light microscopy. The expression rate of CD41a⁺ cells in culture was analysed by flow cytometric.</p><p><b>RESULTS</b>Different concentration of decitabine showed different effect on megakaryocyte growth of steroid-resistant ITP patients and the optimal concentration to differentiate into megakaryocyte for bone marrow mononuclear cells is 3.0 µmol/L. Compared with group A, both megakaryocyte colony forming units (CFU) and expression rate of CD41a⁺ cells in group B were statistically significantly higher (P < 0.05). As compared with group A, the megakaryocyte colony-forming units in group C decreased with statistically significant difference, while compared with group C, the megakaryocyte colony-forming units in group D obviously increased with statistically significant difference.</p><p><b>CONCLUSIONS</b>Decitabine is able to induce bone marrow mononuclear cells of steroid-resistant ITP patients to differentiate into megakaryocyte and the optimal concentration is 3.0 µmol/L; ITP plasma is able to inhibit the megakaryocyte growth of steroid-resistant ITP patients.</p>

Disorder of copper homeostasis induced by lead exposure among mice and intervention effect of quercetin / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of lead exposure on copper and copper metalloenzyme and the intervention effect of quercetin.</p><p><b>METHODS</b>Twenty-four specific pathogen-free male Sprague-Dawley rats of good health were randomly divided into control group (n = 8), lead acetate group (n = 8), and lead acetate + quercetin group (n = 8). The rats in lead acetate group were poisoned by drinking water with 1 g/L lead acetate for 8 weeks, while the rats in control group were fed by drinking water with sodium acetate of the same volume for 8 weeks; the rats in lead acetate+quercetin group were intraperitoneally injected with quercetin (30 mg × kg-1 × d-1) for 8 weeks while drinking water with lead acetate. The Morris water maze was used to test the learning and memory abilities of rats. The lead and copper levels in the serum, hippocampus, cortex, and bone were measured by graphite furnace atomic absorption spectrometry. The level of advanced glycation end products, activity of Cu/Zn superoxide dismutase (SOD), and content and activity of ceruloplasmin (CP) in the hippocampus and serum were measured using a test kit. HE staining was performed to observe the pathological changes in the hippocampus.</p><p><b>RESULTS</b>The Morris water maze test showed that the latency in lead acetate group (52.50±12.04 s) was significantly longer than that in control group (28.08±7.31 s) (P<0.05), and the number of platform crossings was significantly lower in the lead acetate group than in the control group. Compared with those in the control group, the lead levels in the cortex and hippocampus in lead acetate group increased 2.72-fold and 3.79-fold, and the copper in the cortex and hippocampus, and serum free copper levels in lead acetate group increased 1.15-fold, 1.48-fold, and 6.44-fold. Compared with the control group, the lead acetate group had a lower content of CP in the hippocampus (1.23±0.40 U/mg provs0.78±0.08 U/mg pro) and 31.81%and 19.49%decreases in CP content and Cu/Zn SOD activity. Free copper level in serum was positively correlated with the latency and lead levels in the serum, cortex, and hippocampus. The escape latency of rats in lead acetate + quercetin group was decreased by 42.15% (P<0.05). The lead levels in the cortex and hippocampus in lead acetate + quercetin group (0.246 ± 0.58 µg/g and 0.202±0.049 µg/g) were significantly lower than those in lead acetate group (0.391±0.49 µg/g and 0.546±0.120 µg/g), but the free copper and copper levels in the hippocampus and cortex were not significantly reduced. The lead acetate + quercetin group had higher Cu/Zn SOD activity and CP content in the hippocampus than the lead acetate group (P < 0.05). The light microscope observation showed that the number of cells in the hippocampus was reduced with disordered arrangement in the lead acetate group; with quercetin intervention, the hippocampus damage was reduced.</p><p><b>CONCLUSION</b>Lead exposure results in disorder of copper homeostasis, while quercetin may alleviate the damage induced by lead to some extent.</p>