TetR family transcriptional regulators (TFRs) are widely distributed in bacteria and archaea, and the first discovered TFR was confirmed to control the expression of tetracycline efflux pump in Escherichia coli. TFRs can bind DNAs and ligands. Small molecule ligands can induce conformational changes of TFRs, inhibiting or promoting TFRs to control target gene expression. Currently, TFRs have a wide variety of ligands, including carbohydrates, proteins, fatty acids and their derivatives, metal ions, and so on. Due to the diversity of ligands, TFRs regulate a wide range of physiological processes, from basic carbon metabolism and nitrogen metabolism to quorum sensing and antibiotic biosynthesis. On the basis of the recent studies in our laboratory and the literature, we review here the regulatory mechanism mediated by ligands of TFRs in primary and secondary metabolism, as well as the application of ligands for TFRs in the development of gene route and the activation of antibiotic biosynthesis.
Anti-Bacterial Agents ; Bacteria/metabolism* ; Bacterial Proteins/metabolism* ; Gene Expression Regulation, Bacterial ; Ligands ; Quorum Sensing

Objective To investigate the effect of G protein?coupled estrogen receptor (GPER) on the diastolic function of renal interlobular artery and reduce renal ischemia?reperfusion injury in rats. Methods Female ovariectomized rats were divided into control group; ischemia?reperfusion injury (IRI) group;GPER?specific agonist (G1) intervention group;GPER?specific blocker+GPER?specific agonist (G15+G1) intervention group. Histopathological examination (HE staining), renal function test and Paller score were used to identify the success of the model and the degree of kidney damage. In vitro microvascular pressure diameter measuring instrument was used to detect the relaxation and contraction activity of renal interlobular artery in each group. Immunofluorescence technique was used to observe the expression of GPER on the renal interlobular artery. Westernblotting was used to detect the expression of GPER protein in renal interlobular artery of rats in each group. The NO content was determined by a nitrate reductase method. Results Compared with IRI group, serum BUN, Scr level and Paller score in G1 intervention group were significantly decreased (all P<0.05). The systolic rate of renal interlobar artery was significantly increased [(40.76 ± 1.57)％ vs (29.78 ± 1.87)％, P<0.05]. The results of immunofluorescence showed that GPER was expressed in renal interlobular artery smooth muscle cells and endothelial cells, and the expression of IRI group was higher than that of the control group. The expression of G15+G1 intervention group was lower than that of G1 intervention group (all P<0.05). Compared with the IRI group, the NO content in the G1 intervention group increased significantly (all P<0.05). Conclusions During renal ischemia ?reperfusion injury, GPER may regulate the systolic and diastolic activity of the renal interlobar artery by increasing the content of NO, so as to alleviate the renal ischemia?reperfusion injury.

Objective:To compare the therapeutic characteristics of anterior hybrid decompression and posterior cervical posterior laminectomy in the treatment of multilevel cervical spondylotic myelopathy.Methods:Thirty six cases of multilevel cervical spondylotic myelopathy patients treated by anterior hybrid decompression and thirty three cases of multilevel cervical spondylotic myelopathy patients treated by posterior cervical posterior laminectomy were involved.The general information,bleeding amount,operative time,cervical curvature D value,JOA score and incidence of postoperative complications of the two groups before and after surgery were compared.Results:There was no significant difference in the general information among the two groups(P＞0.05),including age (anterior group:56.23± 7.64 years old,posterior group:55.76± 8.18 years old),sex (anterior group:22 males/14 females,posterior group:20 males/13 females),cervical curvature D value (anterior group:7.41± 3.14,posterior group:8.19± 2.74),JOA score (anterior group:9.08± 1.09 scores,posterior group:8.82± 1.26 scores),disease course (anterior group:17.24± 7.36 months,posterior group:15.75± 5.78 months) and affected segment (anterior group:3.11 ± 0.26 segments,posterior group:3.24± 0.39 segments).The the amount of bleeding in the anterior group (anterior approach:221.79± 178.02 ml,posterior group:483.07± 434.25 ml) was lower than that of the posterior group(P＜0.05).The operative time (anterior group:196.54± 51.88 mins,posterior group:175.12± 54.93 mins) was longer,but there was no significant difference (P＞0.05).The cervical curvature D value and JOA score of posterior group were increased with the extension of surgery time.However,the cervical curvature D value of posterior group was decreased,but JOA score was increased.The incidence of bone unfinished,hoarseness and cerebrospinal fluid leakage were found in the anterior group,and axial pain and C5 nerve root paralysis were found in the posterior group.But there was no significant difference in the incidence of complications between the two groups (anterior group 14.89％,posterior group:12.12％)(P＞0.05).Conclusions:Anterior hybrid decompression and posterior cervical posterior laminectomy had their own advantages in the treatment of multilevel cervical spondylotic myelopathy.,The appropriate treatment should be taken according to the condition of patients.

Objective To investigate the effect of estrogen (E2) on the connexin43 (Cx43) expression of renal interlobar arteries after renal ischemia-reperfusion injury (I/R).Methods The experiment was carried out in vivo using an SD rat I/R model.SD rats were randomly divided into normal group,sham-operation group,I/R group,and estrogen-intervention group.The functional changes of the kidney were analyzed after 24 hours of I/R;nephridial tissue section was stained by hematoxylin-eosin (HE),and Paller scores were used to evaluate the degree of kidney damage.Pressure myography was utilized to detect the vasomotor function of renal interlobar arteries.Immunofluorescence technique,qRT-PCR and Western blot were applied to determine the expression of Cx43 in renal interlobar arteries in different groups.Results Estrogen markedly decreased the levels of Cr and BUN in the serum of I/R rats (P＜0.05),and the damage of the kidney tissue could be improved noticeably.The vasomotor rate of renal interlobar arteries was (24.80 ± 3.70)％ after I/R and (41.60 ± 3.50)％ after treatment with estrogen,which was higher than that of I/R group (P＜0.05).The expression of Cx43 was lower in renal interlobar arteries of estrogen-intervention group than that in I/R group (P＜0.01).Conclusion Estrogen may reduce vascular tension and boost dilation of the artery by inhibiting Cx43 expression and GJ function.Therefore,estrogen may attenuate the damage of I/R and improve renal function.

Objective To observe the expression of PAR2 and TMEM16A in the model of chronic constriction injury (CCI) in rat dorsal root ganglion (DRG) neurons,and to explore the role of it in the neuropathic pain.Methods Rats were divided into Sham operation group (Sham) and CCI group.Both groups were observed respectively to determine thermal withdrawal latency (TWL).The expression of PAR2 and TMEM16A in the dorsal root ganglion of the rat was analyzed using Western blot and immunofluorescence.Results The difference in preoperative TWL between CCI group and Sham group rats was not statistically significant (P ＜ 0.01).TWL was signifi cantly lower at all other time points after operation (P ＜ 0.01).Immunofluorescence results showed that PAR2 and TMEM16A coexisted in rat DRG neurons.Western blot results showed that,compared with Sham group,CCI group PAR2 and TMEM16A protein expression significantly increased after 7 d and 14 d (P ＜ 0.01),and the PAR2 and TMEM16A protein expression on 14 d is higher than that of 7 d (P ＜ 0.05).Conclusions Expression level of PAR2 and TMEM16A in CCI group was significantly higher than those in Sham group.The expression level of these proteins may be the cause of rat model of neuropathic pain.

Objective To explore the relationship between KCNJ11-E23K polymorphism and essential hypertension (EH) in Kazakh from Xinjiang. Methods PCR-RFLP method was used to test KCNJ11-E23K genotypes of Kazakh from Xinjiang,including 237 EH patients and 221 normotension (NT). Logistic regression analysis was used to analyze the risk factors associated with EH. Results The frequencies of KCNJ11-E23K genotype (EE and (EK + KK)) and allele (E and K) were 34.18%, 65.82%, 61.60% and 38.40%respectively in EH group. There was a significant difference between two groups (P < 0.05). Weight and EE genotype were risk factors affecting EH in Kazakh from Xinjiang. Individual who carried EE genotype and allele E were 2.501 and 1.388 times than (EK + KK) and allele K suffered from EH respectively. Conclusion KCNJ11-E23K polymorphism was associated with EH in Kazakh from Xinjiang.

Objective To investigate the effects of propofol on mesenteric artery in SD rats and to observe whether the effect of propofol on the mesenteric artery relaxation is related to the gap. Methods Pressure myograph was used to examine the effect of 18β-GA and 2-APB on the relaxation induced by propofol 1×10 -7 ,3×10 -7 ,1×10 -6 ,3×10 -6 ,1 ×10 -5 ,3 ×10 -5 ,1 ×10 -4 and 3 ×10 -4 mol/L in acutely separated mesenteric arterioles of SD rat.Results The diameter of mesenteric arteri-oles were increased from (208.6±13.4)to (213.5±13.6),(21 9.7±13.2),(226.4±12.5),(234.9 ±12.3),(245.5±13.0),(267.4±1 5.2),(336.2±18.3)and (385.9 ±14.2)μm after application of 1×10 -7 ,3×10 -7 ,1 × 10 -6 ,3 × 10 -6 ,1 × 10 -5 ,3 × 10 -5 ,1 × 10 -4 and 3 × 10 -4 mol/L propofol,re-spectively.Propofol induced dilation of the rat mesenteric arterioles in a concentration-dependent man-ner (P < 0.01 ).After pretreatment with 18β-GA and 2-APB,1 × 10 -4 mol/L propofol induced dilation was absolutely decreased (P <0.01).Conclusion These results suggest that propofol relaxes mesenteric arterioles via gap junction.

Objective To investigate the effect of multidrug resistance-associated protein (MRP) 5 silenced by small interfering ribonucleic acid (siRNA) on the multi-drug resistance of human hepatocellular carcinoma (HCC) cells. Methods Multi-drug resistance human HCC cells HepG2/epirubicin(ADM) were constructed and MRP5-siRNA fragment was synthesized. The cells were transfected with Lipofectamine 2000. The experiment was divided into three groups. HepG2/ADM cells transfected with MRP5-siRNA were allocated in the siRNA group, HepG2/ADM cells in the drug resistance group and HCC cells HepG2 in the common group. The cellular sensitivity to chemotherapy agents was detected by MTT assay. The relative expression of MRP5 messenger ribonucleic acid (mRNA) was detected by real-time fluorescence quantiifcation RT-PCR. The expression of MRP5 protein was detected by Western blot. Cellular apoptosis was detected by flow cytometry. Multiple groups were compared by one-way ANOVA and two groups were compared by LSD-t test or t test. Results The half-inhibitory concentration (IC50) of cells for ADM, lfuorouracil (5-FU) and oxaliplatin (OXA) in the drug resistance group was (0.317±0.035), (3.785±0.523) and (0.129±0.009) mg/L, significantly higher compared with (0.022±0.008), (0.163±0.010) and (0.080±0.012) mg/L in the common group (t=14.202, 11.993, 13.937;P<0.05). The IC50 for the three chemotherapy drugs in the siRNA group was (0.180±0.008), (1.657±0.014) and (0.055±0.007) mg/L, signiifcantly lower than those in the drug resistance group (LSD-t=-6.609,-7.044,-11.257;P<0.05). The relative expression level of MRP5 mRNA in the drug resistance group was 3.858±0.481, signiifcantly higher compared with 1.000±0.374 in the common group (LSD-t=9.600, P<0.05). The relative expression level of MRP5 mRNA in the siRNA group was 1.377±0.141, signiifcantly lower than that in the drug resistance group (LSD-t=-11.669, P<0.05). The gray value of MRP5 protein was 2 245 in the drug resistance group, signiifcantly up-regulated compared with 58 in the common group. The gray value of MRP5 protein was 816 in the siRNA group, signiifcantly down-regulated compared with that in the drug resistance group. The cell apoptosis rate in the siRNA group was (25.1±3.7)%, significantly higher compared with (3.3±0.7)% in the drug resistance group (t=9.950, P<0.05). Conclusions MRP5 is associated with the multi-drug resistance of human HCC cells. MRP5 gene silenced by siRNA can enhance the sensitivity of HCC cells towards chemotherapy drugs.

Objective To study the clinical value of orbital magnetic resonance imaging(MRI) in diagnosis and making a judgment about the curative effect of glucocorticoid in patients with Graves' ophthalmopathy (GO).Methods A total of 106 patients with GO were divided into active GO group or inactive GO group according to whether clinical activity score(CAS) ≥3 or not,respectively.T2 relaxation times(T2RTs) (ms) and areas(mm2) of four extra-ocular muscles (EOMs) (superior,inferior,medial,and lateral rectus) were directly measured by MRI T2-Mapping.Correlation analysis of T2 RTs and areas with eyeball motility,diplopia,exophthalmus,visual acuity and intraocular pressure (IOP) were also performed.The T2RTs and areas of EOMs before and after intravenous methylprednisolone(iv MP) pulse therapy were recorded,respectively.Results The mean T2RTs (88.9 ± 13.8)and mean areas(58.1 ± 23.8) of EOMs in active GO were significantly greater than those in inactive GO (80.6 ± 10.0and 46.2 ± 18.6,respectively),bing both significantly greater than those in volunteers with normal eyes(76.2 ±4.7and 30.3 ± 6.1,respectively) (P＜0.01).Maximal T2RTs and maximal areas of EOMs showed significant positive correlation(P＜0.01),and both were positively correlated weakly with CAS,reduced movement of eyeball,diplopia,exophthalmus and loss of visual acuity (P＜0.01).On the contrary,maximal T2RTs and maximal areas of EOMs showed negative correlation or no correlation with spontaneous retrobulbar pain,painful eye movement,redness of eyelids and abnormal IOP.Even if 1 ≤ CAS＜3,ophthalmic symptoms and signs also showed a positive responses to iv MP in patients with moderate to severe GO as long as prolonged T2RTs occurred at least in one of EOMs.The maximal T2RTs,maximal areas,mean T2RTs and mean areas of EOMs were significantly decreased at the end of iv MP treatment,meanwhile ophthalmic symptoms and signs were obviously improved.Conclusions Prolonged T2RTs,especially accompanied by enlarged area on the identical EOMs is an remarkable symbols of acute inflamed muscles.The findings suggested that the use of prolonged T2RTs can improve diagnostic sensitivity and predict the curative effect of iv MP in patients with moderate to severe GO and CAS ≥ 1.

Objective To investigate the relationship between the single nucleotide polymorphism (SNP)of KCNJ1 1 (inwardly rectifying potassium channel,subfamily J,member 1 1)gene and essential hypertension (EH)in Xinjiang Kazak population.Methods The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP ) method was used to detect genotypes of rs2285676 polymorphism of KCNJ1 1, including 126 hypertensives (EH group)and 126 normotensives (NT group)in Xinjiang Kazak population.Multiple-factor unconditional Logistic regression analysis was used to evaluate the risk factors for hypertension in Xinjiang Kazak. Results Logistic regression analysis showed that KCNJ1 1-rs2285676 genotypes,sex,weight,total cholesterol and triglyceride were not associated with hypertension;body mass index (BMI)and high-density lipoprotein (HDL) were protective factors affecting hypertension while low-density lipoprotein (LDL ) was a risk factor for hypertension.Genotypes (TT,CT and CC)and allele frequencies (T and C)of the SNP of rs2285676 in KCNJ1 1 gene were 50.00%,48.41%,1.59%,74.21% and 25.79% in EH group,respectively.The differences between EH and normal control were not significant (P >0.05).Conclusion The rs2285676 polymorphism of KCNJ1 1 is not associated with EH in Xinjiang Kazak population.