Effect of Decomposed Zuoguiwan Recipes in Improving BMD of Ovariectomized Rats by Regulating OPG/RANKL Pathway Mediated by β2AR / 中国实验方剂学杂志

Objective:To investigate the mechanism of decomposed Zuoguiwan（ZGW） recipes in treating ovariectomized osteoporosis rats. Method:Forty Sprague-Dawley female rats were equally and randomly divided into Sham-operated group, ovariectomized model group, positive group, and low and high-dose ZGW groups. After 12 weeks of administration by gavage, the bone mineral density (BMD) of rats' distal femur was measured by micro-CT, the morphology of bone tissue were observed by hematoxylin-eosin staining (HE), β-cross-linked c-telopeptide of type Ι collagen (β-CTX) and bone-specific alkaline phosphatase (BALP) in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of β2AR, OPG and RANKL were evaluated by Western blot analysis and real-time quantitative polymerase chain reaction （PCR）. Result:Compared with Sham-operated group, BMD of rats in ovariectomized model group was decreased (P<0.01), morphology of bone tissue was destroyed, serum BALP was reduced, while β-CTX was boosted (P<0.01)，mRNA and protein expressions of OPG in tibia were reduced, while RANKL were increased, and mRNA and protein expressions of β2AR in the hypothalamus were decreased (P<0.05, P<0.01). Compared with ovariectomized model group, BMDs of rats in low and high-dose ZGW groups were increased (P<0.01), morphology of bone tissue was repaired, serum BALP and mRNA and protein expressions of OPG in tibia were up-regulated (P<0.05, P<0.01), whereas serum β-CTX and mRNA and protein expressions of β2AR in the hypothalamus and RANKL in tibia were down-regulated (P<0.05, P<0.01). Conclusion:Yang-nourishing components in decomposed Zuoguiwan recipes can improve BMD of ovariectomized rats by regulating OPG/RANKL pathway mediated by β2AR. "Seeking Yin in Yang" is a crucial mechanism of Zuoguiwan in treating ovariectomized osteoporosis in rats.

Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β2AR / 中国实验方剂学杂志

Objective: To investigate the mechanism of Zuoguiwan in treating ovariectomy-induced osteoporosis rats by receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway mediated by β2-adrenergic receptor (β2AR). Method: Forty Sprague-Dawley female rats were randomly divided into Sham-operated group (Sham) and four ovariectomized (OVX) subgroups. Rats in Sham and OVX groups were treated with 17β-estradiol (50 μg·kg-1·d-1), and low and high-dose ZGW (2.3,4.6 g·kg-1 lyophilized powder) for 3 months, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum markers of bone turnover. Micro-CT was used to evaluate and measure trabecular bone microarchitecture and bone mineral density (BMD) of the right distal femur. Western blot analysis and Real-time PCR were used to measure mRNA and protein expressions of β2AR, OPG and RANKL. Result: After 12 weeks of treatment with Zuoguiwan, the level of serum β-cross-linked c-telopeptide of type Ι collagen (β-CTX) (PPPβ2AR in the hypothalamus (PPConclusion: The mechanism of Zuoguiwan in alleviating BMD and trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats might be related to the regulation of RANKL/OPG Pathway mediated by β2AR.

Correlation between expression of β2 adrenergic receptors and HER2, K-ras genes in breast cancer / 中华内分泌外科杂志

Objective To investigate the expression of β2 adrenergic receptor (β2 AR) in invasive ductal carcinoma of the breast,and their correlation with HER2 and K-ras genes in breast cancer.Methods The expression of β2 AR,HER2 and K-ras gene in 10 cases of normal breast tissues and 33 cases of invasive ductal carcinoma of the breast were detected by immunohistochemical staining of streptomycin antibiotin protein and peroxidase assay (SP).Such statistical methods as SPSS17.0 statistical software,Mann-Whitney test and Spearman rank correlation test were applied to process and analyze the experimental data.Results β2 AR was expressed in all breast cancer cells,with an overexpression rate of 21/33.The positive expression rate of HER2 in breast cancer cells was 23/33,with an overexpression rate of 20/33.K-ras was positively expressed in breast cancer tissue(28/33),with an overexpression rate of 11/33.All of these three were significantly higher than those in the normal breast tissues.Z value of β-2 AR expression was 4.876,P value was 0.000.Z value of HER2 expression was 2.752,and P value was 0.006.Z value was 3126,and P value was 0.020 for K-ras expression.In the study of the correlation of β2 AR expression with HER2 and K-ras,the expression of β2 AR and HER2 and the expression of β2 AR and K-ras were correlated.The difference in expressions of β2 AR was statistically significant only in groups with or without lymph node metastasis,but not in groups varied in age,tumor size,clinical stage,pathological grading or hormone level.Conclusion The high expression of β2 AR,HER2,and K-ras in breast cancer tissues is associated with the occurrence and development of breast cancer.There is also a greater risk of potential lymph node metastasis in breast cancer with high expression of β-2 AR.β-2 AR may play a role in pathogenesis of breast cancer through HER2 and K-ras.

The activation of α₂-adrenergic receptor in the spinal cord lowers sepsis-induced mortality

The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 µg/27 µl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 µg/5 µl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor α (TNF-α) induced by sepsis. Clonidine administered i.t. or i.p. increased p-AMPKα1 and p-AMPKα2, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of p-AMPKα1 and p-AMPKα2, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.

β2 adrenergic receptor gene polymorphism and coronary atherosclerotic heart disease / 中国生化药物杂志

Objective To investigate the association between β2-adrenergic receptor gene polymorphism and coronary atherosclerotic heart disease, and to provide reference for clinical disease prevention and treatment.MethodsThe clinical data of 200 patients with coronary atherosclerotic heart disease confirmed by coronary angiography were selected and included in the study group, and 200 healthy subjects without coronary atherosclerotic heart disease group.The polymorphism of β2 adrenergic receptor gene was detected and the frequency of each gene was analyzed.ResultsThe genotype frequencies of β2-adrenergic receptor gene were in accordance with Hardy-Weinberg equilibrium, the difference was not statistically significant.According to dominant genetic model, the frequency of AA+AG was 46.0% vs 58.0% lower than that of the control group, and had statistical significance, The genotype frequency of GG genotype in study group was significantly lower than that in control group 14.0% vs 26.0%, χ2=26.20, P=0.00.The frequency of GG genotype in study group was significantly higher than that in control group 54.0% vs 42.0%, χ2=5.76, P=0.01.The frequency of A gene was 38.0% compared with 44.0% in control group, χ2=1.48, P=0.22;the frequency of AA gene in study group was 30.0%, and the frequency of gene A was 38.0%, compared with 56.0% Compared with 32.0% in the control group, χ2=0.18, P=0.66.ConclusionThe A/G polymorphism of β2-adrenergic receptor gene is closely related to the clinical pathogenesis of coronary atherosclerotic heart disease, and the A allele may be a protective factor in patients with coronary atherosclerotic heart disease.

Borneol promotes catalpol and puerarin crossing through blood-brain barrier in focal cerebral ischemic rats / 中国中药杂志

Previous studies showed that borneol could promote some drugs crossing through the blood-brain-barrier (BBB) at certain conditions. However, the mechanism has not been clarified yet. This study aimed to investigate the effect of bornrol on promoting catalpol and puerarin through BBB and explore the relevant mechanism. The focal cerebral ischemic rats were divided into 7 groups randomly and then were administered corresponding drugs: model group (M, solvent), catalpol-puerarin group (ZG, catalpol 45 mg•kg⁻¹+puerarin 200 mg•kg⁻¹), catalpol-puerarin-bornrol group(ZGB, catalpol 45 mg•kg⁻¹+puerarin 200 mg•kg⁻¹ +bornrol 200 mg•kg⁻¹), catalpol-bornrol group(ZB, catalpol 45 mg•kg⁻¹ +bornrol 200 mg•kg⁻¹), puerarin-bornrol group(GB, puerarin 200 mg•kg⁻¹ +bornrol 200 mg•kg⁻¹), butoxamine-ZG group(BTX+ZG, butoxamine 1.5 mg•kg⁻¹+ catalpol 45 mg•kg⁻¹+puerarin 200 mg•kg⁻¹), and butoxamine-ZGB group(BTX+ZGB, butoxamine 1.5 mg•kg⁻¹+ catalpol 45 mg•kg⁻¹+puerarin 200 mg•kg⁻¹ +bornrol 200 mg•kg⁻¹). Another 10 sham-operated rats were set as control (S). Ten minutes after the administration, the cerebrospinal fluid was taken to test the content of catalpol and puerarin, and the brain tissue was taken to test the expression of β2-adrenergic receptor, eNOS, and NO. Compared with the M group, the ZG group showed content of catalpol is 26.673 μg•L⁻¹ and the content of puerarin is below the detection limit;the expression levels of β2-adrenergic receptor, eNOS and the contents of NO in brain tissue are no significant difference. Compared with the ZG group, the ZGB, ZB and GB groups showed significantly increased content of catalpol andpuerarin, as well as the expression of β2-adrenergic receptor, eNOS and NO in the brain tissue (P<0.05). The content of catalpol in BTX+ZG group changed non-significantly. Compared with the ZGB group, the BTX+ZGB group presented significantly decreased content of catalpol and puerarin and reduced expression of eNOS and NO in the brain tissue (P<0.05）.The results demonstrated that borneol could dramatically promote catalpol and puerarin crossing through BBB in the focal cerebral ischemic rats. Moreover, the effect may be related to the up-regulation of β2-adrenergic receptor and the increasing expression of eNOS and NO.

Expression of beta 2 adrenergic receptor in infantile hemangiomas tissue / 中华医学美学美容杂志

Objective To detect the expression of beta 2 adrenergic receptor in the infantile hemangiomas (IH) tissue and to explore its role in the pathological evolution of infantile hemangiomas as well.Methods 48 cases of infantile hemangioma were divided into two groups.29 cases were in the proliferating period,while the other 19 cases were in non-proliferating period.By using immunofluorescence technology,the endothelial nuclei and beta 2 adrenergic receptor of the IH tissue were marked by fluorescent tags,respectively,in two groups.The location of fluorescent labeling was shown in photos.By using the Image-Pro Plus 6.0 software,we analyzed and compared the average fluorescence intensity of endothelial cell nucleus and beta 2 adrenergic receptors in these two groups.Results Beta 2 adrenergic receptors were widely expressed in IH tissue,especially in endothelial cell nucleus shown in fluorescent images.The average fluorescence intensity of endothelial cell core in proliferating IH group was 0.031 ±0.002,which was much higher than that of fading period IH group (0.022±0.002).There was significant statistical different (P＜0.05).The average fluorescence intensity of beta 2 adrenergic receptor in proliferating IH group was 0.035± 0.003,which was much higher than that of fading period IH group (0.028± 0.002).There was significantly statistical different between the two groups (P＜0.05).Conclusions Beta 2 receptors are widely expressed in the endothelial cells of infantile hemangioma.

Correlation between the polymorphism ofβ2-AR and the labor progress after labor analgesia / 临床麻醉学杂志

Objective To investigate the distribution ofβ2-adrenergic receptor (β2-AR)genetic polymorphisms among the included parturient women and observe the relationship between the genetic polymorphisms and labor progress after labor analgesia.Methods A prospective observational study was conducted from March to June in 2014 at Nanjing Maternity and Child Health Care Hospi-tal.A total of 1 65 nulliparous women were enrolled in the study,and finally 1 52 patients were includ-ed after exclusion for several reasons.Theβ2-AR gene polymorphic variations at nucleotides encoding amino acids 1 6 and 27 were detected by polymerase chain reaction-restriction fragment length poly-morphism technique.And the demographic data,rate of oxytocin usage,length of labor progress and the incidence of cesarean section after labor analgesia were observed and recorded.Results The allele frequencies ofβ2-AR genetic polymorphism in the parturient women were dominantly presented in the form of Arg1 6Arg (AA)and Arg1 6Gly (AG)at 1 6 position and Gln27Gln(CC)at 27 position respec-tively.The demographic and background characteristics of the subjects didn’t present any significant differences among the groups with differentβ2-AR genetic polymorphism.And the differences of labor progress among β2-AR 27 genetic polymorphisms parturient women were not significant.However, the length of the first stage and the total labor progress in the β2-AR Arg1 6Arg homozygous were both significantly longer than that in the other two groups (P <0.05),and the incidence of cesarean section was also significantly higher (P <0.05 ).Furthermore,we also found that β2-AR Arg1 6Arg homozygous was related to cesarean delivery after labor analgesia through multivariate logistic regres-sion analysis (OR 2.87,95%CI 2.69-3.09).Conclusion The labor progress of the parturient women with β2-AR Arg1 6Arg homozygous is relatively slower,which maybe an important risk for the nullip-arous women transforming to cesarean delivery after labor analgesia.

Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse / Cell migration and invasion of oral cancer via activation of beta 2 adrenergic receptor by stress mediator

A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das...

The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy...

Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse / Cell migration and invasion of oral cancer via activation of beta 2 adrenergic receptor by stress mediator

A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das...

The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy.

Association between Beta Adrenergic Receptor Polymorphism and Ischemic Stroke: A Meta-Analysis / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: The purpose of this meta-analysis was to determine the precise association between beta-2 adrenergic receptor (beta2AR) polymorphism and Ischemic stroke. METHODS: Published case control studies on association between beta2AR and ischemic stroke were searched from electronic databases. Pooled Odds ratio and 95% Confidence interval were calculated by using software RevMan version 5.2. RESULTS: A total of three studies involving 1,642 cases and 1,673 controls, which were published from 2007 to 2014, were subjected to meta-analysis for allelic association and 518 cases and 510 controls for genotypic association. Pooled analysis of two studies for genotypic association suggested that subjects carrying Gln27Glu polymorphism of beta2AR had an increased risk for Ischemic stroke under recessive model (OR 2.09; 95% CI; 1.20 to 3.64) and under dominant model (OR 1.47; 95% CI 1.14 to 1.90). Pooled analysis of three studies for allelic association showed a significantly higher Glu27 allele of beta2AR in the patients with ischemic stroke (OR 1.58; 95% CI; 1.38 to 1.81). CONCLUSIONS: The present meta-analysis suggests that Gln27Glu polymorphism of beta2AR gene is associated with increased risk for ischemic stroke.

The relationship between β2-adrenergic receptor polymorphisms and early onset Myasthenia Gravis / 中国神经精神疾病杂志

Objective To explore the correlation of β2-adrenergic receptor (β2-AR) polymorphisms (Arg16Gly) with early onset Myasthenia Gravis (MG). Methods Forty-eight with age less than 40 years at disease onset were divided into three groups:normal thymus (13 cases), thymic hyperplasia (22 cases) and thymoma (7 cases) groups according to the thymus histology. These patients were further divided into different subgroups including female (31 cases) and male groups (17 cases) based on the gender, OMG (29 cases) and GMG (19 cases) groups according to the symptom of disease onset and groups associated with (10 cases) or without (33cases) other autoimmune diseases Or with unknown causes (5 cases). The genotypes ofβ2-AR in 48 early onset MG were determined by gene sequencing. Results Arg/Arg was more common in early MG patient with normal thymus ( 53.8%)and thymic hyperplasia(54.6%)whereas Arg/Gly was more common in thymus group(71.4%). The difference in distribution of the genotypes between the three groups was not statis?tically significant (χ2=5.657,P=0.226). Arg/Arg was more common in early female MG patient (58.1%) and Arg/Gly was more common in male MG patients (58.8%). The difference in distribution of the genotypes between the two groups was statistically significant (χ2=6.064,P=0.048). Arg/Arg was more common in early OMG patient (48.3%). Arg/Arg(42.1%) and Arg/Gly(47.4%) were equal common in GMG patients. The difference in distribution of the genotypes between the two groups was statistically significant ( χ2=1.623,P=0.444). Arg/Arg was more common in early MG patient associated with other autoimmune diseases (80.0%). Arg/Gly was more common in MG patients without other autoimmune diseases (39.4%). The difference in distribution of the genotypes between the three groups was statistically significant (χ2=6.394, P=0.041). Conclusionβ2-AR gene polymorphism in position 16 is associated with gender and other autoimmune diseas?es in patients with early onset of MG.

A Combination of Molecular Simulation and Network Methods for Analysis of Conformation Variation in Activation Process of β2 Adrenergic Receptor / 分析化学

To fill the urgent need of researches on the structure and function of proteins to obtain conformation information, we combined targeted molecular dynamics ( TMD) simulation with protein network methods to analyze conformation variations in the activation process of β2 adrenergic receptor. First, targeted MD was used to obtain the conformation resembles in the activation process, and then the protein network method was applied to identify the key residues and pathways in the activation process. The results indicate that the activa-tion process of β2 adrenergic receptor involves in the cooperation of all regions and the connector region of transmembrane helices is signaling hubs. In addition, the helix ends, including intracellular and extracellular loops, are the core areas. The pathway analysis reveals that there is more than one signaling pathway. All the pathways start from Ser204 of the ligand pocket and finally transmit to NPxxY or ICL2 region, which are depended on the different pathways. While the helix TMIII, TMV, TMVI are the important areas in all the pathways. The observations from the work provide valuable information at molecular level for unraveling the signal transduction mechanism associated with the activation process.

Antiallodynic effects of intrathecal tianeptine in a neuropathic pain rat

BACKGROUND: Tianeptine is an antidepressant drug which is used for treating depression. Interestingly, the tianeptine has shown antinociceptive effects within a variety of nociceptions. The aim of this study is to investigate the antiallodynic effects of tianeptine in neuropathic pain rats and also determine the involvements of serotonergic, alpha-2 adrenergic and adenosine receptors at the spinal level. METHODS: Neuropathic pain was induced by ligation of left lumbar at 5th and 6th spinal nerves in male Sprague-Dawley rats. PE-10 catheters were placed into the thoracolumbar subarachnoid space for drug injections. Mechanical allodynia was evaluated by measuring the withdrawal threshold to von Frey filament when applying on the plantar surface of rats. The effects of intrathecal tianeptine were observed at 15, 30, 60, 90, 120, 150, 180 minutes after delivery. Antagonists for serotonergic (dihydroergocristine), alpha-2 adrenergic (yohimbine) and adenosine (CGS 15943) receptors were intrathecally administered 10 minutes prior to tianeptine in order to evaluate the involvement of both receptors. RESULTS: Intrathecal tianeptine increased dose-dependently at the withdrawal threshold in the ligated paw. Pretreatment with intrathecal dihydroergocristine, yohimbine and CGS 15943 antagonized the antiallodynic effects of tianeptine. CONCLUSIONS: These results suggested that intrathecal tianeptine attenuates the spinal nerve ligation induced tactile allodynia. Serotonergic, alpha-2 adrenergic and adenosine receptors are all involved in the antiallodynic effects of tianeptine at the spinal level.

Effect ofβ2-adrenergic receptor expression on migration of early-EPCs in COPD patients / 中国病理生理杂志

AIM:To investigate whether early endothelial progenitor cells (early-EPCs) expressβ2-adrenergic receptor (β2 AR) in the chronic obstructive pulmonary disease ( COPD) patients and the effect of β2 AR expression on the migration of early-EPCs.METHODS:Venous blood samples (20 mL) were obtained from antecubital vein of COPD pa-tients or healthy controls .Peripheral blood mononuclear cells were isolated by standard Ficoll gradient centrifugation , and purified by CD34 positive selection cocktail .The mRNA expression of β2 AR in the early-EPCs was detected by RT-PCR. The protein levels of β2 AR were assessed by Western blotting and flow cytometry .Chemotaxis was studied by Transwell as-say.Cultured early-EPCs were treated with ICI118551, norpinephrine (NE) or monoclonal antibody of β2AR (mAb-β2 AR) for 24 h.The number of migratory cells was counted under a light microscope .RESULTS:The level of β2 AR ex-pression in the COPD patients was higher than that in the controls .The number of migratory early-EPCs to stromal cell-de-rived factor 1αwas significantly improved by ICI 118551 compared with other COPD groups .When early-EPCs from the COPD patients or the controls were treated with different concentrations of mAb-β2 AR for 24 h, the number of migratory early-EPCs from the COPD patients and the controls treated with NE at concentration of 100 nmol/L was significantly re-duced.However, a marked decrease in the number of migratory early-EPCs from the COPD patients treated with NE was observed compared with control group .Before treated with ICI118551 or NE for 24 h, the early-EPCs were co-incubated with mAb-β2 AR for 40 min, and the number of migratory early-EPCs was not significantly different between COPD group and control group .Genetic down-regulation of β2 AR promoted the migration of early-EPCs in COPD group .CONCLU-SION:The level of β2 AR expression in the COPD patients is increased compared with the controls .The down-regulation ofβ2 AR improves the migration of early-EPCs.

Beta-2 adrenergic receptor agonists and acute respiratory distress syndrome / 中国小儿急救医学

Acute respiratory distress syndrome is a serious disease and has a high mortality rate.Protective ventilation strategy and conservative fluid management is the mainstay of treatment and there is no effective pharmacological treatment yet.Recent studies found that beta-2 adrenergic receptor agonists in the treatment of acute respiratory distress syndrome could inhibit the inflammatory response,protect the functions of alveolar capillary barrier,improve pulmonary edema fluid removal,promote the secretion of surfactant and enhance the impaired lung repair,and so on.This review aimed for the pathogenesis,mechanism of action and treatment mechanism of the recent studies.

Dexmedetomidine and Anesthesia.

The α2-adrenoceptors (ARs) by virtue of their sedative, analgesic, sympatholytic, anesthetic-sparing and hemodynamicstabilizing properties, have been used as an adjunct to local anesthetics for prolongation of effect. Dexmedetomidine a stereoisomer of medetomidine a highly selective α2-adrenergic receptor (AR) agonist with a relatively high ratio of α2/ α1-activity (1620:1 as compared to 220:1 for clonidine). It has recently been introduced in anesthesia practice. It is currently being used for continuous intravenous sedation in the intensive care setting and procedural sedation in nonintubated patients.

Tumor Necrosis Factor alpha up-regulates the Expression of beta2 Adrenergic Receptor via NF-kappaB-dependent Pathway in Osteoblasts

Tumor necrosis factor alpha (TNFalpha) is a multifunctional inflammatory cytokine that regulates various cellular and biological processes. Increased levels of TNFalpha have been implicated in a number of human diseases including diabetes and arthritis. Sympathetic nervous system stimulation via the beta2-adrenergic receptor (beta2AR) in osteoblasts suppresses osteogenic activity. We previously reported that TNFalpha up-regulates beta2AR expression in murine osteoblastic cells and that this modulation is associated with TNFalpha inhibition of osteoblast differentiation. In our present study, we explored whether TNFalpha induces beta2AR expression in human osteoblasts and then identified the downstream signaling pathway. Our results indicated that beta2AR expression was increased in Saos-2 and C2C12 cells by TNFalpha treatment, and that this increase was blocked by the inhibition of NF-kappaB activation. Chromatin immunoprecipitation and luciferase reporter assay results indicated that NF-kappaB directly binds to its cognate elements on the beta2AR promoter and thereby stimulates beta2AR expression. These findings suggest that the activation of TNFalpha signaling in osteoblastic cells leads to an upregulation of beta2AR and also that TNFalpha induces beta2AR expression in an NF-kappaB-dependent manner.

Association between Single Nucleotide Polymorphisms of alpha2A-, alpha2B-, and alpha2C-Adrenergic Receptor Genes and Risk of Cerebral White Matter Lesion / 대한뇌졸중학회지

BACKGROUND: An alpha2-adrenergic receptor (alpha2-AR, ADRA2) mediates induction of hypotension and inhibition of lipolysis and insulin secretion. We evaluated whether single nucleotide polymorphisms (SNPs) of alpha2A (ADRA2A), alpha2B (ADRA2B), and alpha2C (ADRA2C) adrenergic receptors are associated with cerebral white matter lesion (cWML). METHODS: Total 336 study subjects who had no stroke were enrolled in this study. The Indices of cWML include total WML (TWML), periventricular WML (PVWML), and subcortical WML (SCWML) on brain fluid-attenuated inversion recovery (FLAIR) image. Common genetic variants of ADRA2A (1780G>A), ADRA2B (Ins/Del301-303), and ADRA2C (Ins/Del322-325) were examined. RESULTS: Among 336 study subjects, cWML was found in 66 patients (20%). In multivariate analysis, there were no significant effects of all tested ADRA2 polymorphisms on TWML. Significant association of ADRA2A 1780 AA genotype was found in PVWML (OR: 3.368, 95% CIs: 1.280-8.865, adjusted p-value after false discovery rate (FDR) correction=0.014) but not SCWML. CONCLUSION: Although SNPs of three ADRA2 subtypes failed to reach a significance in overall risk for cWML, the ADRA2A 1780G>A polymorphism may be associated with development of PVWML.

TNFalpha Increases the Expression of beta2 Adrenergic Receptors in Osteoblasts

Tumor necrosis factor alpha (TNFalpha) is a multifunctional cytokine that is elevated in inflammatory diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Recent evidence has suggested that beta2 adrenergic receptor (beta2AR) activation in osteoblasts suppresses osteogenic activity. In the present study, we explored whether TNFalpha modulates betaAR expression in osteoblastic cells and whether this regulation is associated with the inhibition of osteoblast differentiation by TNFalpha. In the experiments, we used C2C12 cells, MC3T3-E1 cells and primary cultured mouse bone marrow stromal cells. Among the three subtypes of betaAR, beta2 and beta3AR were found in our analysis to be upregulated by TNFalpha. Moreover, isoproterenol-induced cAMP production was observed to be significantly enhanced in TNFalpha-primed C2C12 cells, indicating that TNFalpha enhances beta2AR signaling in osteoblasts. TNFalpha was further found in C2C12 cells to suppress bone morphogenetic protein 2-induced alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes including Runx2, ALP and osteocalcin. Propranolol, a beta2AR antagonist, attenuated this TNFalpha suppression of osteogenic differentiation. TNFalpha increased the expression of receptor activator of NF-kappaB ligand (RANKL), an essential osteoclastogenic factor, in C2C12 cells which was again blocked by propranolol. In summary, our data show that TNFalpha increases beta2AR expression in osteoblasts and that a blockade of beta2AR attenuates the suppression of osteogenic differentiation and stimulation of RANKL expression by TNFalpha. These findings imply that a crosstalk between TNFalpha and beta2AR signaling pathways might occur in osteoblasts to modulate their function.