S-Persulfidation: Chemistry, Chemical Biology, and Significance in Health and Disease.

Significance: S-Persulfidation generates persulfide adducts (RSSH) on both small molecules and proteins. This process is believed to be critical in the regulation of biological functions of reactive sulfur species such as H2S, as well as in signal transduction. S-Persulfidation also plays regulatory roles in human health and diseases. Recent Advances: Some mechanisms underlying the generation of low-molecular-weight persulfides and protein S-persulfidation in living organisms have been uncovered. Some methods for the specific delivery of persulfides and the detection of persulfides in biological systems have been developed. These advances help to pave the road to better understand the functions of S-persulfidation. Critical Issues: Persulfides are highly reactive and unstable. Currently, their identification relies on trapping them by S-alkylation, but this is not always reliable due to rapid sulfur exchange reactions. Therefore, the presence, identity, and fates of persulfides in biological environments are sometimes difficult to track. Future Directions: Further understanding the fundamental chemistry/biochemistry of persulfides and development of more reliable detection methods are needed. S-Persulfidation in specific protein targets is essential in organismal physiological health and human disease states. Besides cardiovascular and neuronal systems, the roles of persulfidation in other systems need to be further explored. Contradictory results of persulfidation in biology, especially in cancer, need to be clarified.

Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity.

The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) treatment in renal mesangial cells and kidney tissue, which was associated with decreased baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression and increased apoptotic rate. Enforced miR-181a expression enhanced 5-FU-induced p53-dependent mitochondrial apoptosis, including declined Bcl-2/Bax ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase-9 and caspase-3 activation. However, inhibition of miR-181a was associated with reduced p53-mediated mitochondrial apoptosis induced by 5-FU. Moreover, miR-181a increased BIRC6 downstream gene p53 protein expression and transcriptional activity by reducing ubiquitin-mediated protein degradation. We found that miR-181a directly targeted 3'-UTR of BIRC6 mRNA and negatively regulated BIRC6 expression. In vivo study, knockdown of miR-181a with adeno-associated virus harboring miR-181a-tough decoy attenuated 5-FU-induced renal cell apoptosis, inflammation and kidney injury. In conclusion, these results demonstrate that miR-181a increases p53 protein expression and transcriptional activity by targeting BIRC6 and promotes 5-FU-induced apoptosis in mesangial cells. Inhibition of miR-181a ameliorates 5-FU-induced nephrotoxicity, suggesting that miR-181a may be a novel therapeutic target for nephrotoxicity treatment during chemotherapy.

[Treating Type 2 Diabetes Mellitus Patients Complicated with Metabolic Syndrome by Benefiting Qi Dissolving Method].

Objective To observe clinical efficacy of Yiqi Huaju Recipe (YHR) combined routine Western medical treatment on type 2 diabetes mellitus (T2DM) patients complicated metabolic syndrome (MetS). Methods Totally 96 T2DM patients complicated MetS were assigned to the treatment group (YHR +routine Western drugs) and the control group (placebo +routine Western drugs) according to random digit table, 48 cases in each group. The therapeutic course for all was 12 weeks. Body mass index (BMI) , waistline, waist-hip ratio (WHR) , fasting plasma glucose (FPG) , 2 h postprandial plasma glucose (2 h PPG) , glycosylated hemoglobin A1c (HbAlc) , homeostasis model assessment of insulin resistance (HOMA-IR) , blood lipids, blood pressure, disease transformation of MetS, changes of con- stituent numbers were detected before and after treatment. Results BMI, WHR, waistline obviously decreased in the treatment group after treatment, with statistical difference as compared with the control group (P<0.01 , P <0.05). Post-treatment FPG, 2 h PPG, HbAlc, HOMA-IR, systolic blood pressure (SBP), diastolic blood pressure (DBP) , and mean artery pressure (MAP) obviously decreased in the two groups, but more obviously in the treatment group (P <0. 05). Post-treatment total cholesterol (TC) , low density lipoprotein cholesterol (LDL-C) , and triglycerides (TG) all obviously decreased in the two groups , but TG decreased more obviously in the treatment group (P <0. 05). High density lipoprotein cholesterol (HDL-C) obviously increased in the treatment group (P <0. 05). Patient numbers of central obesity, uncontrolled hypertension, and uncontrolled diabetes obviously decreased and constituent numbers were obviously reduced in the treatment group after treatment, with better efficacy than those of the control group (P <0. 01 , P <0. 05). Conclusions YHR plus routine Western drugs could further reduce blood glucose, and had comprehensive interventional effects on multiple cardiovascular risk factors such as central obesity, blood lipids, and blood pressure in T2DM patients complicated with MetS. Its mechanism might be possibly correlated with improving insulin resistance and elevating insulin sensitivity of peripheral tissues.

CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy.

The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream signaling pathway during the process of cardiac hypertrophy remain unknown. The present study aims to investigate the relationships between CyPA-CD147-ERK1/2-cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular myocytes were determined by Western blot and immunostaining. Compared with sham groups, systolic blood pressure reached hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were significantly increased at 4 and 8 weeks after clipping. ELISA results indicated a prominent increase in serum CyPA level associated with the degree of left ventricular hypertrophy. Western blot revealed that the expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also remarkably increased as the cardiac hypertrophy developed. The results of the present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2 signaling pathway in ventricular tissues are time-dependently upregulated and activated with the process of left ventricular hypertrophy. These data suggest that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left ventricular hypertrophy.

A distributed parallel genetic algorithm of placement strategy for virtual machines deployment on cloud platform.

The cloud platform provides various services to users. More and more cloud centers provide infrastructure as the main way of operating. To improve the utilization rate of the cloud center and to decrease the operating cost, the cloud center provides services according to requirements of users by sharding the resources with virtualization. Considering both QoS for users and cost saving for cloud computing providers, we try to maximize performance and minimize energy cost as well. In this paper, we propose a distributed parallel genetic algorithm (DPGA) of placement strategy for virtual machines deployment on cloud platform. It executes the genetic algorithm parallelly and distributedly on several selected physical hosts in the first stage. Then it continues to execute the genetic algorithm of the second stage with solutions obtained from the first stage as the initial population. The solution calculated by the genetic algorithm of the second stage is the optimal one of the proposed approach. The experimental results show that the proposed placement strategy of VM deployment can ensure QoS for users and it is more effective and more energy efficient than other placement strategies on the cloud platform.

[Effect of yiqi huaju recipe combined with routine therapy in treating hypertension patients with metabolic syndrome: a clinical study].

OBJECTIVE: To investigate the therapeutic effect of Yiqi Huaju Recipe (YHR) combined with routine therapy on the blood pressure, the blood pressure variability and other cardiovascular risk factors in hypertension patients complicated with metabolic syndrome (MetS). METHODS: Totally 43 hypertension patients complicated with MetS were recruited in this study and randomly assigned to the treatment group (22 cases, treated with basic routine treatment +YHR) and the control group (21 cases, treated with basic routine treatment + placebo). The treatment course was 12 weeks. Detected were parameters such as 24-h ambulatory blood pressure monitoring (ABPM), body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), homeostatic model assessment for insulin resistance (HOMA-IR), fasting glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2 h PPG), fasting plasma insulin (FPI), serum lipid, etc. RESULTS: The anthropometric parameters and plasma glucose levels (except HbAlc) were obviously lowered after treatment than before treatment in the treatment group (P < 0.01, P < 0.05). Besides, better effects were obtained in the WC, WHR, 2 h PPG, FPI and HOMA-IR (P < 0.05). The average blood pressure amplitude, the blood pressure variability, and blood pressure load at any time point were more obviously improved in the two groups after treatment than before treatment (P < 0.01, P < 0.05). Besides, partial indices were better in the treatment group than in the control group (P < 0.01, P < 0.05). CONCLUSIONS: YHR combined with routine therapy exhibited better effect on reducing the blood pressure amplitude, the blood pressure variability, and the blood pressure load in hypertension patients complicated with MetS. It could also effectively decrease the risk of other vascular disease.

Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria: a randomized placebo-controlled trial.

BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE: To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES: Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed. RESULTS: Compared with the control group, CHF treatment significantly decreased BMI (P<0.05), WC (P<0.01) and WHR (P<0.01). Both groups had significant decreases in FPG, 2-hPPG, HbA1c, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P<0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P<0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P>0.05), whereas it significantly increased with CHF treatment (P<0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P<0.01). However, there was no significant difference between the two groups (P>0.05). CONCLUSION: Combined treatment of Yiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

Effects of Chinese herbal medicine Yiqi Huaju Formula on hypertensive patients with metabolic syndrome: a randomized, placebo-controlled trial.

BACKGROUND: Patients with hypertension coupled with metabolic syndrome (MetS) are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebrovascular diseases, it is essential to appropriately control blood pressure together with other cardiovascular risk factors. OBJECTIVE: The current study was designed to investigate the therapeutic effects on blood pressure, blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula, a compound traditional Chinese herbal medicine, in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 43 patients with hypertension coupled with MetS were recruited into this study. The enrolled patients were randomly divided into the Chinese herbal formula group (anti-hypertensive drugs plus Yiqi Huaju Formula, CHF) and the control group (anti-hypertensive drugs plus placebo). The CHF group enrolled 22 patients while the control group received 21 cases. Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES: Parameters examined include 24-hour ambulatory blood pressure monitoring, body mass index, waist circumference, waist-to-hip ratio, homeostatic model assessment for insulin resistance (HOMA-IR), fasting glycosylated hemoglobin (HbA1c), fasting plasma glucose, 2-hour postprandial plasma glucose (PPG), fasting plasma insulin, serum lipid, etc. RESULTS: Compared with the control group, the CHF group had significant improvement (P<0.01) in anthropometric parameters, FPG, HOMA-IR, blood pressure amplitude, blood pressure variability and blood pressure load. CONCLUSION: This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors. The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER: ChiCTR-TRC-11001633.

Caveolin-3 is involved in the protection of resveratrol against high-fat-diet-induced insulin resistance by promoting GLUT4 translocation to the plasma membrane in skeletal muscle of ovariectomized rats.

Insulin resistance is recognized as a common metabolic factor which predicts the future development of both type 2 diabetes and atherosclerotic disease. Resveratrol (RSV), an agonist of estrogen receptor (ER), is known to affect insulin sensitivity, but the mechanism is unclear. Evidence suggests that caveolin-3 (CAV-3), a member of the caveolin family, is involved in insulin-stimulated glucose uptake. Our recent work indicated that estrogen via ER improves glucose uptake by up-regulation of CAV-3 expression. Here, we investigated the role of CAV-3 in the effect of RSV on insulin resistance in skeletal muscle both in vivo and in vitro. The results demonstrated that RSV ameliorated high-fat-diet (HFD)-induced glucose intolerance and insulin resistance in ovariectomized rats. RSV elevated insulin-stimulated glucose uptake in isolated soleus muscle in vivo and in C2C12 myotubes in vitro by enhancing GLUT4 translocation to the plasma membrane rather than increasing GLUT4 protein expression. Through ERα-mediated transcription, RSV increased CAV-3 protein expression, which contributed to GLUT4 translocation. Moreover, after knockdown of CAV-3 gene, the effects of RSV on glucose uptake and the translocation of GLUT4 to the plasma membrane, as well as the association of CAV-3 and GLUT4 in the membrane, were significantly attenuated. Our findings demonstrated that RSV via ERα elevated CAV-3 expression and then enhanced GLUT4 translocation to the plasma membrane to promote glucose uptake in skeletal muscle, exerting its protective effects against HFD-induced insulin resistance. It suggests that this pathway could represent an effective therapeutic target to fight against insulin resistance syndrome induced by HFD.

Dydrogesterone exerts endothelial anti-inflammatory actions decreasing expression of leukocyte adhesion molecules.

Clinical observations and basic studies show that progesterone and progestins have a variable influence on endothelial function. Dydrogesterone (DG) is a widely used progestin, but its endothelial actions have not been thoroughly assessed. In this study, we investigated the effects of DG and its metabolite 20-α-dihydro-dydrogesterone (DHD), natural progesterone as well as medroxyprogesterone acetate, on the expression of leukocyte adhesion molecules in human endothelial cells using an in vitro experimental endothelial inflammation system. Our findings show that all progestins significantly suppress endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and inter-cellular adhesion molecule-1 (ICAM-1) induced by bacterial lypopolysaccharide (LPS). These inhibitory effects of DG and DHD require activation of progesterone receptor. DG and DHD decrease adhesion molecule expression associated with LPS administration by preventing nuclear translocation of the pro-inflammatory transcription factor nuclear factor-κB. In addition, DG and DHD do not alter the anti-inflammatory effects of 17ß-estradiol. In conclusion, DG and DHD decrease endothelial inflammatory responses induced by LPS, via reduced expression of the pro-atherogenic adhesion molecules VCAM-1 and ICAM-1. These actions may be relevant for the vascular effects of DG.

2-Chloro-N-[1-(4-chloro-phen-yl)-3-cyano-1H-pyrazol-5-yl]acetamide.

The title compound, C(12)H(8)Cl(2)N(4)O, was synthesized by the reaction of 5-amino-1-(4-chloro-phen-yl)-1H-pyrazole-3-carbonitrile and 2-chloro-acetyl chloride. The dihedral angle between the pyrazole and benzene rings is 30.7 (3)°. In the crystal structure, strong N-H⋯O hydrogen bonds link the mol-ecules into chains along [001]. C-H⋯N hydrogen bonds are also present.

17 beta-estradiol attenuates pressure overload-induced myocardial hypertrophy through regulating caveolin-3 protein in ovariectomized female rats.

Our findings indicate that in ovariectomized female rats abdominal aortic constriction led to significant increases in left ventricular mass, myocyte diameter and heart weight/body weight (HW/BW) value, and decreases in interventricular septal thickness at diastole (IVSd), left ventricular percent fractional shortening (FS) and ejection fraction (EF). These pathophysiological alterations were largely reversed by administration with 17ß-estradiol for eight weeks. Furthermore, the enhanced expression of extracellular signal-regulated kinases 1/2 and decreased expression of caveolin-3 were found in left ventricle of AAC group. 17ß-estradiol (E(2)) administration increased the expression of caveolin-3 and reduced the level of ERK phosphorylation in these pressure-overloaded rats. Moreover, in cultured neonatal rat cardiomyocytes, E(2) inhibited the hypertrophic response to angiotensin II. This effect was reinforced by the addition of extracellular signal-regulated kinases 1/2 inhibitor PD98059, but was impaired when the cells were pretreated with caveolae disruptor, methyl-ß-cyclodextrin (M-ß-CD). In conclusion, our data indicate that estrogen attenuates the hypertrophic response induced by pressure overload through down-regulation of extracellular signal-regulated kinases 1/2 phosphorylation and up-regulation of caveolin-3 expression.

[Extending hemicelluloses content calibration of Acacia spp using NIR to new sites].

In this research, hemicellulose contents of 78 wood meal samples of Acacia spp trees grown in Guangxi and another 33 wood meal samples of Acacia spp trees grown in Fujian were measured by wet chemistry. NIR spectra were also collected by a Bruker MPA spectrometer within 4 000-12 500 cm(-1) of wavenumbers using a standard sample cup. Equations were developed using partial least squares (PLS) regression and cross validation for multivariate calibration in this study. High coefficients of determination (R2) and low root mean square errors of cross-validation (RMSECV) were obtained for hemicellulose content (R2 = 0.947, RMSECV = 0.464) of Guangxi woodmeal samples. Prediction produced high correlation coefficients between laboratory and predicted values, with R2 and RMSEP values being 0.925 and 0.455, respectively. A variable numbers of Fujian samples ranging from one to thirteen were used to enhance the Guangxi calibration so as to be widely used for routine assessment of wood chemistry. It was demonstrated that the addition of a single Fujian sample to the Guangxi calibration set was sufficient to greatly reduce predictive errors and that the inclusion of 3 Fujian samples in the Guangxi set was sufficient to give relatively stable predictive errors. The R2 is 0.904 and RMSEP is 0.759. The addition of different sets of 3 Fujian samples to the Guangxi calibration, however, caused predictive errors to vary between sets.

[Effects of Fufang Jiangzhi No.3 on cholesterol-bile acid metabolism in rabbits with hypercholesterolemia].

OBJECTIVE: To investigate the effects of Fufang Jiangzhi No. 3, a compound traditional Chinese herbal medicine, on cholesterol-bile acid metabolism in rabbits with hypercholesterolemia and to explore the mechanism. METHODS: Twenty-four male New Zealand white rabbits were randomly assigned into normal control group, untreated group and Fufang Jiangzhi No. 3 group, with 8 rabbits in each group. Rabbits in the untreated group and Fufang Jiangzhi No. 3 group were fed high cholesterol diet to induce hypercholesterolemia. After 4-week treatment, serum total cholesterol and bile acid contents were assessed. Activity of cholesterol 7alpha-hydroxylase (CYP7A1) in liver tissues was measured by enzyme-linked immunosorbent assay. The expressions of CYP7A1, bile salt export pump (BSEP) and small heterodimer partner (SHP) mRNAs in liver tissues were observed by real-time fluorescent quantitative polymerase chain reaction. RESULTS: Compared with the normal control group, serum total cholesterol and bile acid contents in the untreated group were increased (P<0.01). Activity of CYP7A1 and expression of CYP7A1 mRNA were decreased and expressions of BSEP and SHP mRNAs were increased in liver tissues in the untreated group as compared with the normal control group (P<0.01). Serum total cholesterol level, and expressions of BSEP and SHP mRNAs in the Fufang Jiangzhi No. 3 group were lower than those in the untreated group (P<0.01). The CYP7A1 activity and expression of CYP7A1 mRNA in the Fufang Jiangzhi No. 3 group were increased as compared with the untreated group (P<0.01), however, there was no significant difference in bile acid between the Fufang Jiangzhi No. 3 group and the untreated group. CONCLUSION: Fufang Jiangzhi No. 3 can up-regulate the expression of CYP7A1 mRNA, raise the activity of CYP7A1, and inhibit the expressions of BSEP and SHP mRNAs to regulate the metabolism of total cholesterol in rabbits.

Progesterone receptor enhances breast cancer cell motility and invasion via extranuclear activation of focal adhesion kinase.

While progesterone plays multiple roles in the process of breast development and differentiation, its role in breast cancer is less understood. We have shown previously that progestins stimulate breast cancer cell migration and invasion because of the activation of rapid signaling cascades leading to modifications in the actin cytoskeleton and cell membrane that are required for cell movement. In this study, we have investigated the effects of progesterone on the formation of focal adhesion (FA) complexes, which provide anchoring sites for cell attachment to the extracellular matrix during cell movement and invasion. In T47-D breast cancer cells, progesterone rapidly enhances FA kinase (FAK) phosphorylation at Tyr(397) in a time- and concentration-dependent manner. As a result, exposure to progesterone leads to increased formation of FA complexes within specialized cell membrane protrusions. The cascade of events required for this phenomenon involves progesterone receptor interaction with the tyrosine kinase c-Src, which activates the phosphatidylinositol-3-kinase/Akt pathway and the small GTPase RhoA/Rho-associated kinase complex. In the presence of progesterone, T47-D breast cancer cells display enhanced horizontal migration and invasion of three-dimensional matrices, which is reversed by small interfering RNAs abrogating FAK. In conclusion, progesterone promotes breast cancer cell movement and invasion by facilitating the formation of FA complexes via the rapid regulation of FAK. These results provide novel mechanistic views on the effects of progesterone on breast cancer progression, and may in the future be helpful to develop new strategies for the treatment of endocrine-sensitive breast cancers.

Sex steroids and breast cancer metastasis.

Sex steroids, particularly estrogen and progesterone, promote normal breast tissue growth and differentiation. Prolonged exposure of estrogen and/or progesterone is considered a risk factor for breast cancer carcinogenesis, and the effects of sex steroids on breast cancer metastasis are controversial. Emerging evidence indicates that sex steroids regulate breast cancer metastatic processes via nongenomic and genomic mechanisms. Through the regulation of actin-binding proteins estrogen and progesterone rapidly provoke actin cytoskeleton reorganization in breast cancer cells, leading to formation of membrane structures facilitating breast cancer cell migration and invasion. In addition, steroid receptors interact and trans-activate receptor tyrosine kinases (including epidermal growth factor receptor and insulin-like growth factor receptor), resulting in growth factor-like effects that promote cancer cell invasive behavior. Moreover, sex steroids regulate the expression of metastasis-associated molecules, such as E-cadherin, matrix metalloproteinases, growth factors, chemokines and their receptors, leading to epithelial-to-mesenchymal-like transition. However, there is also evidence that sex steroids and their receptors protect against breast cancer cell invasiveness through distinct mechanisms. Here, we present an overview of the currently identified actions of sex steroids on breast cancer metastasis and their potential clinical implications.

Rapid signaling of estrogen to WAVE1 and moesin controls neuronal spine formation via the actin cytoskeleton.

Estrogens are important regulators of neuronal cell morphology, and this is thought to be critical for gender-specific differences in brain function and dysfunction. Dendritic spine formation is dependent on actin remodeling by the WASP-family verprolin homologous (WAVE1) protein, which controls actin polymerization through the actin-related protein (Arp)-2/3 complex. Emerging evidence indicates that estrogens are effective regulators of the actin cytoskeleton in various cell types via rapid, extranuclear signaling mechanisms. We here show that 17beta-estradiol (E2) administration to rat cortical neurons leads to phosphorylation of WAVE1 on the serine residues 310, 397, and 441 and to WAVE1 redistribution toward the cell membrane at sites of dendritic spine formation. WAVE1 phosphorylation is found to be triggered by a Galpha(i)/Gbeta protein-dependent, rapid extranuclear signaling of estrogen receptor alpha to c-Src and to the small GTPase Rac1. Rac1 recruits the cyclin-dependent kinase (Cdk5) that directly phosphorylates WAVE1 on the three serine residues. After WAVE1 phosphorylation by E2, the Arp-2/3 complex concentrates at sites of spine formation, where it triggers the local reorganization of actin fibers. In parallel, E2 recruits a Galpha(13)-dependent pathway to RhoA and ROCK-2, leading to activation of actin remodeling via the actin-binding protein, moesin. Silencing of WAVE1 or of moesin abrogates the increase in dendritic spines induced by E2 in cortical neurons. In conclusion, our findings indicate that the control of actin polymerization and branching via moesin or WAVE1 is a key function of estrogen receptor alpha in neurons, which may be particularly relevant for the regulation of dendritic spines.

[Relationship between lupus headache and headache due to internal injury in traditional Chinese medicine].

In 1999, the nomenclature and case definitions for neuropsychiatric lupus syndromes were published by American College of Rheumatology (ACR), and the cognition of neuropsychiatric damage of systemic lupus erythematosus (SLE) was gradually unified and standardized. Lupus headache is an intractable problem in SLE, especially in SLE patients complicated with multiple organ injury. In general, vascular headache is common in most SLE patients, and a small number of SLE patients complicated with nervous headache are found in clinic. Moreover, its pathophysiological mechanism is far from being understood. Although early diagnosis is essential for good outcomes, the diagnosis method is rather confused in the world. There still exist some limitations in the proposal of clinical classification of headache from ACR and International Headache Society (IHS), and the proposal does not mention the classification of headache related to psychiatric damage. Current therapeutic regimens are almost exclusively based on empirical evidence. Treatment approaches include symptomatic treatment, immunosuppressive, anticoagulant and anti-aggregant therapies. It provides enormous and hopeful space in research of combined therapy strategy, especially in the field of traditional Chinese medicine. The authors discussed the relationship between lupus headache and headache due to internal injury in the view of integrated traditional Chinese and Western medicine, and suggested that the treatment strategy for lupus headache should be made in argument with the headache due to internal injury. Syndrome differentiation treatment according to deficiency in the root and excess in the branch and the therapy for activating blood to dredge collaterals maybe have great advantages in treatment of the headache in SLE.