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Objective:To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats.Methods:Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg -1·min -1 and remifentanil 1.0 μg·kg -1·min -1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T 0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R ( P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated ( P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z ( P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups ( P>0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.
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Objective:To investigate the relationship between S-nitrosylation of spinal divalent metal transporter 1 (DMT1) modification and mechanism of remifentanil-induced hyperalgesia in rats.Methods:Forty pathogen-free healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), L-NAME group (group C+ L) and remifentanil+ L-NAME group (group R+ L). Normal saline was infused at a rate of 0.1 ml·kg -1·min -1 for 60 min via the caudal vein in C group. Remifentanil was infused at a rate of 1.0 μg·kg -1·min -1 for 60 min via the caudal vein in R group. L-NAME 30 mg/kg was intraperitoneally injected, and 10 min later normal saline was infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C+ L group. L-NAME 30 mg/kg was intraperitoneally injected, and 10 min later remifentanil was infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R+ L group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before iv infusion and 6, 24 and 48 h after the end of infusion (T 0-3). All the rats were sacrificed under anesthesia after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of neuronal nitric oxide sythases (nNOS) and DMT1 mRNA (using quantitative real-time polymerase chain reaction), extraction of nitrosylated proteins (by biotin switch assay), expression of nNOS, total DMT1 and S-nitrosylation of DMT1 (by Western blot), nitric oxide (NO) content (by spectrophotometry) and iron content (using atomic absorption spectrophotometer). Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3 in group R ( P<0.05), and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was significantly up-regulated, and contents of NO and iron were increased in R and R+ L groups ( P<0.05), and no significant change was found in each index in group C+ L ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was down-regulated, and contents of NO and iron were decreased in group R+ L ( P<0.05). Compared with group C+ L, the MWT was significantly decreased, and the TWL was shortened at T 1-3, and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was up-regulated, and the contents of NO and iron were increased in group R+ L ( P<0.05). There were no significant differences in the expression of DMT1 mRNA and total DMT1 in spinal cord among all the groups ( P>0.05). Conclusions:Activation of nNOS induces an increase in NO generation in the spinal cord and mediates the S-nitrosylation of DMT1, which may be related to the mechanism of remifentanil-induced hyperalgesia in rats.
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Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.
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Objective To explore the correlation between Triglyceride Glucose Index (TyG) and its combined obesity Index and prehypertension in middle-aged and elderly population in China, and to provide a monitoring tool for better hierarchical management of prehypertension population. Methods A total of 5 099 people with non-hypertension were enrolled through the database of the China Health and Retirement Longitudinal Study (CHARLS). Body mass index (BMI), waist circumference (WC) and waist to height ratio (WTHR) were obtained, and TyG-BMI, TyG-WC and TyG-WTHR indexes were calculated by multiplying the TyG index with the three indexes respectively. Logistic regression analysis was used to explore the relationship between TyG index and obesity index and prehypertension. The DeLong method was used to compare the values of Area Under the Curve (AUC) of each index to distinguish their value in identifying prehypertension. Results Compared with the normal blood pressure group, the prehypertension group was older, and the blood pressure was higher. Logistic regression analysis showed that higher levels of TyG-BMI and TyG-WC index were significantly associated with prehypertension. Compared with the lowest quartile array Q1, the OR values of TyG-BMI Q2-Q4 were 1.24 (95%CI :1.03-1.49), 1.40 (95%CI :1.10-1.76) and 1.91 (95%CI :1.43-2.56), while the OR values of TyG-WC index Q2-Q4 group were 1.45 (95%CI :1.19-1.75), 1.49 (95%CI :1.13-1.95), and 2.12 (95%CI: 1.47-3.07), respectively. There was no statistically significant difference in the AUC value between TyG-WC and TyG-BMI (P =0.0998). Conclusion Among the four novel indexes, higher levels of TyG-WC and TyG-BMI are positively correlated with prehypertension. Compared with TyG and TyG-WTHR, TyG-WC and TyG-BMI have the potential to become an effective auxiliary means in the individual hierarchical management of prehypertension in the middle-aged and elderly.
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Objective To study the level of serum 25 (OH) D3in children in suzhou area, and to provide scientific basis for the rational supplement of vitamin D for children aged 0-6years.Methods From September2015to September 2016, 15 010children underwent routine physical examination in the Children′s Health Clinic of Suzhou Municipal Hospital were selected, of whom 7 905were male and 7 105were female.The serum 25 (OH) D3was detected by collecting their fingerling blood.Results (1) The mean serum 25 (OH) D3of15 010children aged 0to 6in Suzhou was (35.83±13.23) μg/L, and the mean serum 25 (OH) D3of male and female were (36.48±13.25) and (35.11±13.16) μg/L respectively, and the differences were statistically significant (P＜0.01). (2) The mean level of serum 25 (OH) D3of 0-＜3, 3-＜6, 6-＜12, 12-＜36, 36-＜48and≥48months old children were (34.49±11.53), (41.15±13.86), (48.03±17.25), (46.12±17.69), (28.49±16.55) and (42.28±17.59) μg/L.The detection levels of serum 25 (OH) D3between the age groups were statistically significant (P＜0.05) except the children 3-＜6months and≥48months. (3) From January to December, the detection levels of serum 25 (OH) D3 were statistically significant between different months (P＜0.01) except in January, February, March and November, as well as July and August.The serum25 (OH) D3in each month was graded according to the vitamin D level, and the detection levels of serum 25 (OH) D3between different months were statistically significant (P＜0.01).The proportion of serum 25 (OH) D3over 30μg/L was less than 50％in January, March and November.The ratio ranged from 50％to 60％in February, June and December.The ratio ranged from 60％to 70％in the July, August and September, while the proportion was over 70％in April, May and October.Conclusion The level of serum 25 (OH) D3in children in Suzhou area was decreased obviously, and health education should be strengthened, and attention should be paid to intaking of vitamin D in children.
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<p><b>OBJECTIVE</b>To evaluate the toxic effects of mixture of volatile organic compounds (VOCs) on Mice Testis related enzymes and hormones.</p><p><b>METHODS</b>After determining the median lethal dose (LD₅₀) of VOCs using the acute toxicity test, 40 male clean inbred Kunming mice were assigned to 1/8 LD₅₀ VOCs exposure group, 1/4 LD₅₀ VOCs exposure group, and 1/2 LD₅₀ VOCs exposure group, as well as positive control group with cyclophosphamide (60 mg/kg) and negative control group with tea oil, with 8 mice in each group. The mice were intraperitoneally injected with respective agents for 5 days. The levels of testis testosterone, estradiol, follicle stimulating hormone, and luteinizing hormone were determined by ELISA. Meanwhile, the activity of testicular marked enzymes such as lactate dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase, and glucose-6-phosphate dehydrogenase were examined.</p><p><b>RESULTS</b>Compared with the negative control group, the 1/8 LD₅₀ exposure group had a significantly increased testis coefficient (P<0.05). Both the activity of testicular marked enzymes and the levels of testicular sex hormones in all exposure groups showed significant downward trends with increasing VOC doses compared with those in the negative control group (P<0.05).</p><p><b>CONCLUSION</b>VOCs have obvious toxicity to mouse testis by changing the levels of testicular sex hormones and the activity of testicular marked enzymes.</p>
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Animaux , Mâle , Souris , Oestradiol , Chimie , Hormone folliculostimulante , Chimie , Hormones sexuelles stéroïdiennes , Chimie , Hormone lutéinisante , Chimie , Testicule , Chimie , Testostérone , Chimie , Composés organiques volatils , ToxicitéRÉSUMÉ
Objective To investigate the changes of serum osteocalcin and bone micro-structure in ovariectomized mice exposed to low-iron environment.Methods Twenty-four 12-week-old female C57BL/6 mice were divided equally into sham operation (SHAM) group,model(OVX) group,and low iron(OVX+DFO) group.In low-iron group,deferoxamine(DFO) was injected 3 times per week for 5 weeks after operation ; the other groups were injected with the same dose of 0.9％ normal saline for 5 weeks.The serum,left femur,uterus were harvested after five weeks of treatment.The serum osteocalcin and ferritin levels were measured by ELISA kit,the weight of the uterus was recorded by analytical balance.A high resolution micro-CT was used to scan the left femur for cortical bone and cancellous bone analysis.Results (1) The serum osteocalcin and serum ferritin levels in low-iron group were significantly lower than those in the other 2 groups (P＜0.01) ; (2) Compared with the sham group and ovx group,there were significant decrease of the BMD、BV/TV and Tb.N,but increase of Tb.Th and Tb.Sp in low-iron group (P＜0.01).Conclusion A certain dose of DFO (30 mg/kg) can decrease the serum ferritin levels as well as the bone formation index in ovariectomized mice.
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Objective To study the protective effects of parathyroid hormone (PTH) on radiationinduced hematopoietic damage in mice.Methods A total of sixty male C57 mice were irradiated by 60Co γ-rays to induce hematopoietic injuries,and then the mice were randomly divided into PTH and control group.The PTH-treated group was treated with PTH ( 80 μg· kg- 1 · d - 1 ) intraperitoneally everyday.The control group was given equivalent volume saline.Peripheral blood cell number,bone marrow mononuclear cell number,granulocyte-macrophage colony forming units ( CFU-GM ) and CD34 positive cells in bone marrow were detected.Results With the whole post-irradiation period,the WBC and bone marrow mononuclear cell numbers in PTH-treated mice were significantly higher than those in saline-treated mice (t=6.32,9.19,11.18,7.44 and 4.42,P ＜ 0.05).The RBC numbers in PTH-treated mice were significantly higher than those in control mice at 10 d,15 d and 20 d post-irradiation (t =6.48,3.66 and 4.98,P ＜0.05 ).The PLT numbers in PTH-treated mice were significantly higher than those in control group at 5 and 30 d post-irradiation ( t =2.57 and 3.10,P ＜ 0.05 ).PTH increased CD34 positive cell and CFU-GM numbers in bone marrow after irradiation ( t =16.12,7.82 and 20.00,P ＜ 0.05 ).Conclusions PTH could improve the hematopoietic recovery after irradiation.
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<p><b>BACKGROUND AND OBJECTIVE</b>The transport of nucleoside transmembrane mediated by equilibrative nucleoside transporter (ENT) plays an important role in regulating various cellular functions, and the ENT gene may be candidate gene of tumors. The aim of this study is to investigate the association between the single nudcleotide polymorphism (SNP) of ENT3 and the hereditary susceptibility of lung cancer.</p><p><b>METHODS</b>A case-control study was performed involved in 351 lung cancer patients and 207 cancer-free controls from Chinese population in Shanghai pulmonary hospital. The rs10999776 (C>T) polymorphism was determined by using Real-time PCR with AllGlo probes. The frequency distribution of genotypes and allele between lung cancer and controls groups was analyzed by chi-square test. The association between polymorphism in the ENT3 gene with the risk of lung cancer was estimated by computing odds ration (OR) and 95%CI.</p><p><b>RESULTS</b>The genotype (CC, TC, IT) and allele distribution of the ENT3 SNP in the patients with lung cancer was not significantly different compared with that in controls (P > 0.05). Compared with never-smokers with wild homozygous genotype, smokers with T allele (TC+TT) had increased risk of lung cancer (OR = 2.848, 95% CI: 1.536-4.879, P = 0.005), and those with pack-years of smoking more than 30 had higher risk (OR = 3.076, 95% CI: 2.308-6.741, P = 0.001). And the risk of squamous cell carcinoma significantly increased in smokers, especially those with T allele (TC+TI) genotype (OR = 6.066, 95% CI: 2.884-12.758, P < 0.001). The genotype with smoking conditions had no significant effect on adenocarcinoma (all P > 0.05).</p><p><b>CONCLUSION</b>The results suggested rs10999776 polymorphism may implicate in the risk of squamous cell carcinoma in Chinese population which may interact with smoking-exposure.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Prédisposition génétique à une maladie , Tumeurs du poumon , Génétique , Transporteurs de nucléosides , Génétique , Polymorphisme de nucléotide simple , FumerRÉSUMÉ
Objective To investigate the effect of vitamin D (VD) on macrophage to phagocytize Staphylococcus aureus (SA). Method Macrophoge cell lines RAW264.7 were allocated into 3 groups:control group(C),bacterium group(B),active vitamin D+ bacterium group (VD+B). Cells in the VD+B group were incubated with 10-8mol/L active vitamin D for 24h,then cells in the VD+B group and the B group were cultured with SA for 1h,and phagocytosis rate,mitochondrial membrane potential,[Ca～(2+)]i,reactive oxygen species were determined by flow cytometry (FCM). Results The phagocytizing activity of macrophage in VD+B group was significantly higher than that in B group 1h after infection,At the same time,the mitochondrial member potential and [Ca～(2+)]i of macrophage in VD+B group were distinctly lower than that in B group; but reactive oxygen species of macrophage in the VD+B group was insignificantly different from B group. Conclusion Vitamin D can reinforce the phagocytizing activity of macrophage and inhibit the apoptosis of macrophage after phagocytize Staphylococrcus aureus.