Objective To investigate the effect of luxS inactivation on the oxidative stress of Streptococcus mutans and perform preliminary analysis of potential mechanism.Methods Strains were grown to mid-logarithmic phase and divided into three groups,one was used as control and inoculated into normal TPY medium,and the other two groups were experimental groups,and there were separately inoculated into TPY containing 58.8 mmol/L hydrogen peroxideor TPY containing 58.8 mmol/L hydrogen peroxide and 0.1 mmol/L 2,2'-dipyridyl.The survival rate of strain was calculated at 0.5,1,and 2 h.All the data were statistically analyzed.Results Compared with the control group,the survival rate of luxS mutation was always higher than standard strain at all pre-determined time inexperimental groups (P＜0.05),and compared with experimental group without iron chelator,the survival rate of strains was not raised with the added of iron chelator (P＞0.05).Conclusion luxS gene is involved in oxidative stress tolerance of Streptococcus mutans,and the oxidative stress tolerance is not achieved by avoiding the toxic effects of the Fenton reaction

Autoimmune diseases (AID) are characterized by autoimmune disorder, as autologous tissue is attacked by the autoimmune system. It is reported that the imbalance of autoimmune tolerance and ingrained inflammatory response are the core events of AID undoubtedly. Peroxisome proliferator-activated receptor γ (PPARγ) which belongs to the nuclear hormone receptor superfamily is a ligand activated transcription factor. PPARγ combines with retinoid X receptor (RXR) to form heterodimer. When PPARγ is activated, the complex regulates gene expression by binding to a specific peroxisome proliferator response element (PPRE). In addition, PPARγ has diversified biological functions, playing important roles in regulating metabolism, controling inflammation, modulating glucose and lipid metabolism, ameliorating atherosclerosis, anti-tumor, and regulating immune response. However, recently researches indicate that PPARγ participates in the pathogenesis of AID. PPARγ plays key roles in regulating activation and polarization of macrophages, function of dendritic cells, proliferation and differentiation of T cells, and modulation of the function of related stromal cells. This article summarizes the biological functions and signal transduction pathways of PPARγ and the protective effects of agonists of PPARγ on AID, aiming to provide theoretical support for the research of mechanism and prevention and treatment of AID.

Adult ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; therapeutic use ; CD3 Complex ; metabolism ; Colitis, Ulcerative ; drug therapy ; Diagnosis, Differential ; Drug Hypersensitivity ; etiology ; metabolism ; pathology ; Female ; Gastrointestinal Agents ; adverse effects ; therapeutic use ; Humans ; Immunoblastic Lymphadenopathy ; metabolism ; pathology ; Ki-1 Antigen ; metabolism ; Lymphadenitis ; chemically induced ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Lymphoma, T-Cell ; metabolism ; pathology ; Receptors, Complement 3d ; metabolism ; Sulfasalazine ; adverse effects ; therapeutic use

OBJECTIVETo investigate the expression of transcription factors (TF) T-bet and GATA-3 mRNA in peripheral blood mononuclear cells and its correlation with immune status in esophageal cancer patients.

METHODSSixty patients were divided into two groups according to the clinical data: group A consisting of stage I and II, group B including stage III and IV. The gene expression of T-bet and GATA-3 in 60 esophageal cancer patients and 30 healthy controls was detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of IFN-gamma and IL-4 was measured by enzyme linked immunosorbent assay (ELISA).

RESULTSExpression of T-bet mRNA in esophageal cancer patients (stage I and II: 0.27 +/- 0.05 ng/L, stage III and IV: 0.12 +/- 0.02 ng/L) was significantly lower than that in the healthy controls (1.35 +/- 0.14 ng/L), but the expression of GATA-3 mRNA in esophageal cancer patients (stage I and II: 0.45 +/- 0.06, stage III and IV: 0.55 +/- 0.03) was significantly higher than that in the healthy controls (0.09 +/- 0.10). The plasma level of Th1 cytokine IFN-gamma in the patients [stage I and II: (12.12 +/- 1.48) ng/L, stage III and IV: (8.44 +/- 0.90) ng/L] was significantly lower than that in the healthy controls, while the level of Th2 cytokine IL-4 in the patients [stage I and II: (18.64 +/- 0.77) ng/L, stage III and IV: (25.28 +/- 2.02) ng/L] was significantly higher than that in the healthy controls. However, neither in the expression of T-bet and GATA-3, nor in the plasma level of IFN-gamma and IL-4, showed a significant difference between group A and B.

CONCLUSIONIn the peripheral blood of esophageal cancer patients, the expression of T-bet decreased, while GATA-3 increased, Th1/Th2 balance is broken, and the Th2 is dominant. T-bet and GATA-3 play a part role in the regulation of Th1/Th2 balance.

Adult ; Aged ; Aged, 80 and over ; Enzyme-Linked Immunosorbent Assay ; Esophageal Neoplasms ; immunology ; metabolism ; pathology ; Female ; GATA3 Transcription Factor ; genetics ; metabolism ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Neoplasm Staging ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; T-Box Domain Proteins ; genetics ; metabolism ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

Objective To observe the radiosensitivity by targeting HIF-lα in human lung cancer and the effects on tumor growth in nude mice.Methods Radiosensitivity of A549 and A549/HIF-1α ( － ) cells were tested by clonogenic forming assay.A549/HIF-1 α( － ) cells and A549 cells were injected into the male BALB/C nude mice.Tumor growth was observed.The expression of HIF-1α and microvessel density were detected by immunohistochemistry method.Results SERs of HIF-1α gene silencing were 1.03 in normoxia and 1.65 in hypoxia.The sizes of tumor xenografts derived from A549/HIF-1α( － ) cells were significantly reduced compared to those of the xenografts derived from A549 cells.HIF-1 α protein staining result showed a dramatic decrease in tumors from A549/HIF-1α ( － ) mice.The microvessel densities (MVD) were 19.83 ± 4.09 in A549 group and 11.61 ±3.04 in A549/HIF-lα (-)group(F=15.57,P ＜0.05 ).Conclusions Hypoxia-induced radio-resistance in lung cancer A549 cells could be reversed by silencing the HIF-1α.It also retards the growth of tumor xenografts,decreases HIF-1α expression and reduces the vascularity.

DNA Replication ; physiology ; Epstein-Barr Virus Infections ; virology ; Herpesvirus 4, Human ; genetics ; metabolism ; physiology ; Humans

Objective To determine the impact of fluorine and aluminum,and both action combined on the number of rat osteoclasts and bone resorption cultured in vitro and to explore its mechanisms.Methods The osteoclasts and bone marrow stromal cells (BMSCs) isolated from long bone of new born rats were cultured,respectively,in TC199 medium (containing 10％ fetal bovine serum) with fluoride,aluminum and fluoride combined with aluminum.The osteoclasts were inoculated in 96-well culture plate and ivory slice,BMSCs in 6-well culture plate,and culture medium was changed after 2 hours incubation.The cells were divided into control group,fluoride group,aluminum group and fluoride combined with aluminum group; the doses of sodium fluoride were 0,1.0 × 10-4,0,1.0 × 10-4 mol/L and the doses of aluminum chloride were 0,0,1.0 × 10-5,1.0 × 10-5 mol/L,respectively.Tartrate-resistant acid phosphatase (TRAP) staining positive cells were counted under light microscope after TRAP staining on the 5th day and the pit formed in ivory slices were measured by histomorphometry after staining with toludine blue.The expression of osteoprotegerin(OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) was detected by real-time fluorescence quantitative PCR in BMSCs after 8 h treatment.Results ① Fluoride,aluminum and the interactive effects of fluoride and aluminum all had impact on the numbers of osteoclasts (F =7.15,6.56 and 7.98,respectively,all P ＜ 0.05).The numbers of osteoclasts in fluoride group,aluminum group and fluoride combined with aluminum group[(136.9 ± 22.99),(135.4 ± 23.5),(163.0 ± 24.4) per well] were higher than that in the control group[(92.5 ± 22.1) per well,all P ＜ 0.05].② Fluoride,aluminum and the interactive effects of fluoride and aluminum all had impact on the resorption pit area on ivory slices(F =10.47,12.64,14.29,respectively,all P ＜ 0.05).The resorption pit area on ivory slices in fluoride group,aluminum group and fluoride combined with aluminum group[(0.242 ± 0.031),(0.293 ± 0.026),(0.333 ± 0.016)mm2 per slice] was higher than that in the control group [(0.088 ± 0.030)mm2 per slice,all P ＜ 0.05].③Fluoride,aluminum and the interactive effects of fluoride and aluminum all had impact on the expression ratios of RANKL/OPG in BMSCs (F =8.15,15.38,23.59,respectively,all P ＜ 0.05).The expression ratios of RANKL/OPG in BMSCs in fluoride group,aluminum group and fluoride combined with aluminum group [(193.98 ± 137.93)％,(326.11 ± 176.78)％,(599.84 ± 275.82)％] were higher than that in the control group[(100.00 ± 56.02)％,all P ＜ 0.05].Conclusions Both fluoride and aluminum can cause increase in the number of osteoclasts in vitro and promote cell differentiation and bone resorption activity,which may be related to increased expression ratio of RANKL/OPG mRNA in BMSCs.The stimulating effects of fluoride on osteoclasts differentiation and bone resorption is enhanced by aluminum.

Objective To investigate the efficacy and clinical effectiveness of the steroid therapy with the all body and local application on hyperthyroid Graves ophthalmopathy.Methods A total of 57 patients (106 eyes)suffering from hyperthyroid Graves ophthalmopathy who hospitalized in the Department of Ophthalmology of the Second Affiliated Hospital of Harbin Medical University from Mar 2008 to Oct 2011 were enrolled in the study.Of the 57 patients,there were 21 males and 36 females,aged 18 to 57(average 37.28 ± 11.63).The clinical course was from 1 month to 5 years(average 29.63 ± 15.36 months).Based on the patient's age,sex and condition,the 57 patients were randomly divided into steroid pulse therapy with all body group(group SPT,29 patients,54 eyes)and peribulbar injection of long-term steraid group(group PI,28 patients,52 eyes).The patients in group SPT were treated with 0.5-l.0 g methylprednisolone by intravenous infusion daily for 3 days,and then stopped for 7 days,the treatment was repeated once.But the total application dose of methylprednisolone was not overruned 5.0-20.0 g.After that,the patients were treated with oral prednisone 40 mg/d.The dose of prednisone was reduced gradually to 5 mg/d.The total course of group SPT was 3 months.The patients in the group PI were treated with triamcinolone acetonide in periorbital injection of 20 mg once every two weeks for 3 months.After one month treated,all patients were visited.The patients' body weights of two groups were measured before the treatment and after one month treated.The ocular signs of the patients including visual acuity,diplopia,intraocular pressure,exophthalmos and horizontal visual palpebral fissure width were observed before and after the treatment.Results In the group SPT,the average body weight [(62.83 ± 7.23)kg]after the treatment was higher than that before the treatment[(57.03 ±7.13)kg],and also higher than that of the group PI[(59.89 ± 10.67)kg,t =25.25,2.08,all P＜ 0.05]after the treatment.In the group SPT,the average intraocular pressures before and after the treatment were (13.46 ± 1.78)and (13.69 ± 1.41)mm Hg(1 nm Hg =0.133 kPa),respectively.In the group PI,the average intraocular pressures before and after the treatment were (13.52 ± 2.19) and (13.77 ± 2.03)mm Hg,respectively.There was no significant differences before and after the treatment in both gr0ups(P＞ 0.05).In the group SPT and PI,the average exophthalmos after the treatment[(18.63 ± 2.22) and (14.85 ± 2.61)mm]were lower than those before the treatment[(20.78 ± 2.24) and (20.60 ± 2.81)mm,t =9.97,29.68,all P＜ 0.05],respectively.After the treatment,the average exophthalmos in the group PI was significantly lower than that of the group SPT(t =7.79,P＜ 0.05).In the groups SPT and PI,the average averagepalpebral fissure width after the treatment[(15.00 ± 1.80) and (11.65 ± 2.45)mm]were lower than those before the treatment[(17.22 ± 1.89) and (17.44 ± 2.37)mm,t =22.74,91.24,all P ＜ 0.05].After treatment of the group PI,the average exophthalmos was significantly lower than that of the group SPT(t =8.01,P ＜ 0.05).Conclusion Compared with the steroid pulse therapy with all body,the peribullbar application of long-term hormone for hyperthyroid Graves ophthalmopathy is more effective,with lcss side effects and worthy of promotion.

Objective To determine the effects of fluoride on osteoclasts's quantity and bone resorption function in vitro and its mechanisms. Methods The osteoclasts and bone marrow stromal cells(BMSCs) isolated from long bone of new born rats were cultured respectively in TC199 medium (containing 10% fetal bovine serum) with fluoride. The osteoclasts were inoculated in 96-well culture plate and ivory slice, BMSCs were inoculated in 6- well culture plate, respectively, medium were changed after 2 hours incubation. They were divided into control group, low-dose fluoride, medium-dose fluoride and high-dose fluoride groups, the doses of sodium fluoride were 0,2.5 × 10-5,5.0 × 10-5,10.0 × 10-5 mol/L, respectively. Tartrate-resistant acid phosphatase(TRAP) staining positive cells were counted under light microscope after TRAP staining on the 2nd and the 5th day and the pit formed in ivory slices were measured by histomorphometry after staining with toludine blue. The expression of receptor activator of NK-κβ ligand(RANKL) and osteoprotegerin(OPC) was detected by real-time fluorescence quantitative (337.5 ± 70.5), (447.5 ± 43.4), (472.9 ± 34.8), (475.3 ± 24.3)/well in the control group, the low-dose, mediumdose and high-dose fluoride groups, respectively. The differences were statistically significant between these groups and the control group (all P < 0.05). After in vitro culture for 5 days, the numbers of osteoclasts were (92.5 ± 22.1), (123.0 ± 26.4), (135.5 ± 22.2), (136.9 ± 23.0) per well in the control group, the low-dose, medium-dose and high-dose fluoride groups, respectively. The differences were statistically significant between these groups and the (0.088 ± 0.030), (0.100 ± 0.018), (0.152 ± 0.015), (0.242 ± 0.031 )mm2 per piece in the control group, the lowdose, medium-dose and high-dose fluoride groups, respectively. The values of medium-dose and high-dose fluoride BMSCs in the control group, the low-dose, medium-dose and high-dose fluoride groups were 100.00 ± 56.02, 144.95 ± 97.21,223.25 ± 184.48,193.98 ± 137.93, respectively. The values of medium-dose and high-dose fluoride groups were significantly higher than that of control group (all P < 0.05). Conclusions Fluoride can cause increase in the number of osteoclasts in vitro and promote their cell differentiation and bone resorption activity, which may be related to increased expression ratio of RANKL/OPG mRNA in BMSCs.