[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.

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.

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.

Effects of raloxifene on breast cancer cell migration and invasion through the actin cytoskeleton.

Raloxifene (RAL) is a selective oestrogen receptor modulator (SERM) approved for the prevention and treatment of osteoporosis and for the prevention of breast cancer in postmenopausal women. However, little is known on the effects of this SERM on breast cancer cell metastasis, which is the main cause of morbidity and death. Cell movement is critical for local progression and distant metastasis of cancer cells. These processes rely on the dynamic control of the actin cytoskeleton and of cell membrane morphology. The aim of the present study was to characterize the effects of RAL or of 17beta-estradiol (E2) plus RAL on oestrogen receptor (ER) positive T47-D breast cancer cell cytoskeletal remodelling, migration and invasion. Our findings show that, when given alone, RAL induces a weak actin cytoskeleton remodelling in breast cancer cells, with the formation of specialized cell membrane structures implicated in cell motility. However, in the presence of physiological amounts of estradiol, which potently drives breast cancer cell cytoskeletal remodelling and motility, RAL displays a powerful inhibitory effect on oestrogen-promoted cell migration and invasion. These actions are plaid through an interference of RAL with an extra-nuclear signalling cascade involving G proteins and the RhoA-associated kinase, ROCK-2, linked to the recruitment of the cytoskeletal controller, moesin. Hence, in the presence of estradiol, RAL acts as an ER antagonist. These results highlight a novel mechanism of action of the SERM raloxifene that might be important for the interference of breast cancer progression or metastasis induced by oestrogens in postmenopausal women.

[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.

Effects in postmenopausal women of estradiol and medroxyprogesterone alone and combined on resistance artery function and endothelial morphology and movement.

CONTEXT: Endothelial dysfunction in resistance arteries after menopause is important for the development of high blood pressure and cardiovascular disease. OBJECTIVES: Our objectives were to study the effects of different hormone replacement therapies on the function and morphology of isolated resistance arteries, and to look for their mechanistic basis. DESIGN AND SETTING: This was a randomized, placebo-controlled double-blind study in a University hospital, along with laboratory based studies. PATIENTS AND INTERVENTIONS: We isolated resistance arteries in sc biopsies from 55 postmenopausal women before and after 3-month therapy with estradiol (E2), medroxyprogesterone acetate (MPA), E2 plus MPA, or placebo. In addition, we studied isolated human endothelial cells. MAIN OUTCOME MEASURES AND RESULTS: Artery flow-mediated dilatation was augmented after treatment with E2 or E2 plus MPA, whereas MPA or placebo had no effect. Pressure-induced myogenic tone was reduced by E2 plus MPA, whereas it was unchanged in the other groups. Scanning microscopy showed that E2 improved endothelial cell morphology and decreased signs of endothelial apoptosis, but the addition of MPA impaired these events. E2, MPA, or the combination all increased the expression and phosphorylation of the actin-binding protein, moesin and of the focal adhesion complex controller, focal adhesion kinase, and induced the rearrangement of cytoskeletal actin and vinculin fibers. All treatments promoted endothelial cell horizontal migration, with E2 inducing the strongest effect. CONCLUSIONS: This study suggests that hormone replacement therapy with estrogens or in combination with MPA may benefit the function of resistance arteries and may preserve the morphological integrity of endothelial cells by regulatory actions on the cytoskeleton.

Progestogens regulate endothelial actin cytoskeleton and cell movement via the actin-binding protein moesin.

The endothelial effects of progestogens are poorly investigated. Actin remodeling and cell movement are fundamental for endothelial function and are controlled by the actin-binding protein moesin. In this work, we studied the effects of progesterone and medroxyprogesterone acetate (MPA) on actin remodeling, moesin activation and cell movement in human endothelial cells. Our findings show that progesterone and MPA trigger a rapid endothelial actin rearrangement, with the formation of cortical actin complexes, pseudopodia and membrane ruffles. Both progestogens trigger a rapid progesterone receptor (PR)-dependent moesin activation via a non-genomic signaling cascade involving G proteins, the small GTPase RhoA and the Rho-associated kinase (ROCK-2). In addition, MPA signaling also requires the recruitment of phosphatidylinositol-3 kinase (PI3K). Both progestogens enhance endothelial cell migration, which is prevented by moesin silencing or by blockade of PR, G proteins, PI3K, mitogen-activated protein kinases or ROCK-2. Progesterone and MPA potentiate 17beta-estradiol (E2) induced-moesin activation. However, they partially reduce cell migration induced by E2. In conclusion, progesterone and MPA regulate endothelial cell movement by rapidly signaling to the actin-binding protein moesin and to the actin cytoskeleton. These findings provide new information on the biological actions of progestins on human endothelial cells that are relevant for vascular function.

Extra-nuclear signaling of estrogen receptors.

Estrogen controls multiple biological functions through binding to estrogen receptors (ERs). Traditionally, ERs have been regarded as transcription factors regulating the expression of target genes. However, growing evidence of rapid estrogen's actions in a number of tissues has been accumulating and alternative mechanisms of signal transduction have been proposed. These so called "extra-nuclear actions" do not require gene expression or protein synthesis and are independent of the nuclear localization of ERs. Indeed, some of these actions are elicited by ERs residing at or near the plasma membrane. Membrane-associated molecules such as ion channels, G proteins, the tyrosine kinase c-Src as well as growth factor receptors are modulated by liganded ERs within the membrane, leading to the activation of downstream cascades such as mitogen-activated protein kinase, phosphatidylinositol 3-OH kinase, protein kinase A, and protein kinase C. These cascades mediate some important rapid actions of estrogen, such as the activation of nitric oxide synthesis or the remodeling of actin cytoskeleton. In addition, these pathways are critical for the regulation of the expression of a number of target proteins implicated in cell proliferation, apoptosis, differentiation, movement, and homeostasis. In this manner, the extra-nuclear pathways are tightly integrated with the genomic pathways to orchestrate the full spectrum of estrogen's biological functions. The recent advancements in the characterization of the molecular basis of the extra-nuclear signaling of estrogen helps to understand the role of estrogen on human cells, and may in future turn out to be of relevance for clinical purposes.

Effects of phytoestrogens derived from red clover on atherogenic adhesion molecules in human endothelial cells.

OBJECTIVE: In the search for safer approaches to address menopausal symptoms, the administration of plant-derived estrogens has gained popularity. Recent evidence suggests that these compounds may act neutrally or even beneficially on surrogate cardiovascular risk markers in postmenopausal women. However, little is known of the effects of phytoestrogens on vascular cells. DESIGN: Endothelial expression of leukocyte adhesion molecules plays a critical role in the development of atherosclerosis and in plaque destabilization, and estrogen reduces the expression of these proatherogenic molecules. We studied the regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) and of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells by phytoestrogens contained in red clover extracts. Moreover, we characterized the mechanistic basis for these actions. RESULTS: Red clover extracts, particularly genistein and daidzein, inhibit the endothelial expression of ICAM-1 and VCAM-1 induced by bacterial lipopolysaccharide. The addition of red clover extracts to reproductive life or menopausal concentrations of 17beta-estradiol results in an additive decrease in expression of endothelial adhesion molecules. The reduction of ICAM-1 and VCAM-1 expression in the presence of red clover extracts is paralleled by a cytoplasmic stabilization of the proinflammatory transcription factor nuclear factor-kappaB. CONCLUSIONS: Red clover extracts act as anti-inflammatory and antiatherogenic agents on human endothelial cells by reducing the expression of the leukocyte adhesion molecules ICAM-1 and VCAM-1. On the basis of these results, red clover extracts may induce beneficial actions on human vessels.

Comparative actions of progesterone, medroxyprogesterone acetate, drospirenone and nestorone on breast cancer cell migration and invasion.

BACKGROUND: Limited information is available on the effects of progestins on breast cancer progression and metastasis. Cell migration and invasion are central for these processes, and require dynamic cytoskeletal and cell membrane rearrangements for cell motility to be enacted. METHODS: We investigated the effects of progesterone (P), medroxyprogesterone acetate (MPA), drospirenone (DRSP) and nestorone (NES) alone or with 17beta-estradiol (E2) on T47-D breast cancer cell migration and invasion and we linked some of these actions to the regulation of the actin-regulatory protein, moesin and to cytoskeletal remodeling. RESULTS: Breast cancer cell horizontal migration and invasion of three-dimensional matrices are enhanced by all the progestins, but differences are found in terms of potency, with MPA being the most effective and DRSP being the least. This is related to the differential ability of the progestins to activate the actin-binding protein moesin, leading to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. E2 also induces actin remodeling through moesin activation. However, the addition of some progestins partially offsets the action of estradiol on cell migration and invasion of breast cancer cells. CONCLUSION: These results imply that P, MPA, DRSP and NES alone or in combination with E2 enhance the ability of breast cancer cells to move in the surrounding environment. However, these progestins show different potencies and to some extent use distinct intracellular intermediates to drive moesin activation and actin remodeling. These findings support the concept that each progestin acts differently on breast cancer cells, which may have relevant clinical implications.

[Effects of tongxinluo capsule on cardiac ventricle remodeling after myocardial infarction: a multicentre clinical research].

OBJECTIVE: To investigate the effects of tongxinluo (TXL) capsule on cardiac ventricle remodeling after acute myocardial infarction (AMI). METHODS: Seventy AMI patients were randomly divided into 2 equal groups: conventional therapy group treated with conventional Western therapy and TXL treatment group treated with TXL capsule for 6 weeks in addition to the conventional treatment. Cardiac color ultrasound was conducted before and 6 weeks after the treatment to examine the changes of ventricular structure, mass and function. Radioimmunoassay was used to detect the levels of angiotensin II (Ang II) and endothelin-1 (ET-1). RESULTS: Six weeks later, the left ventricular posterior wall thickness of end-diastolic (LVPWTD), left ventricular end-systolic dimension (LVESD), and left atrium dimension (LAD) of the TXL group were 0.93 cm +/- 0.09 cm, 3.71 cm +/- 0.19 cm, and 3.21 cm +/- 0.29 cm respectively, all lower than those before treatment (0.93 cm +/- 0.09 cm, 3.71 cm +/- 0.19 cm, and 3.21 cm +/- 0.29 cm respectively) and those of the conventional treatment group (0.95 cm +/- 0.08 cm, 3.62 cm +/- 0.46 cm, and 3.82 cm +/- 0.30 cm) (all P < 0.05), the ejection-fraction (EF) improvement rate of the TXL group was 63% +/- 7%, significantly higher than that before treatment (52% +/- 6%) and that of the conventional treatment group (59% +/- 8%, both P < 0.05). CONCLUSION: TXL capsule in addition to conventional therapy has a positive effect on the prognosis of AMI via reversing the ventricular remodeling, and improving cardiac function.

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.