Aim To explore the pharmacological mechanism and the effects of polysaccharide sulfat(PSS) on cardiovascular diseases induced by type 2 diabetes mellitus(DM) through observing the risk factors.Methods Type 2 diabetic animal model was established by high-sugar and high-fat diets,combined with injection of small amount streptozotocin(STZ 20 mg?kg-1,iv).Adult male wistar rats were divided into five groups: normal control group,model group,polysaccharide sulfate group,metformin group and lovastatin group.They were treated with exact medicne for 8 weeks,but control group and model group were treated with 0.9% Nacl.During this process,FBG and serum lipid concentrations were measured.22 weeks later,the rats were sacrificed.The activity of tissue-type plasminogen activator(t-PA) and plasminogen activator inhibitor type-1(PAI-1) were detected by chemical methods.The aortas were collected for histopathlogical,immunohistochemical and Western blot studies.Results FBG concentrations and serum lipid(TC,TG,LDL) levels decreased in PSS group as compared from those of model group(P

Animals ; Female ; Fluorosis, Dental ; blood ; etiology ; Glutathione Peroxidase ; blood ; Male ; Malondialdehyde ; blood ; Myocytes, Cardiac ; pathology ; ultrastructure ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sinoatrial Node ; pathology ; ultrastructure ; Sodium Fluoride ; poisoning ; Superoxide Dismutase ; blood

Adult ; Breast Neoplasms ; metabolism ; pathology ; secondary ; Carcinoid Tumor ; metabolism ; pathology ; surgery ; Carcinoma, Adenoid Cystic ; pathology ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hysterectomy ; Keratins ; metabolism ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Ovarian Neoplasms ; metabolism ; pathology ; Sex Cord-Gonadal Stromal Tumors ; metabolism ; pathology ; Synaptophysin ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; surgery

A novel drug delivery system combining oral fast dissolving film with sodium deoxycholate/phospholipid mixed micelles was prepared to increase the absorption of cucurbitacin B that is a poor aqueous solubility substance. Encapsulation efficiency, particle size, zeta potential, polydispersity coefficient, investigated the morphology, disintegration time of oral fast dissolving film and the pharmacodynamic properties of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles before and after solidified in mice were evaluated and compared. The oral fast dissolving film prepared in this study showed a homogeneous pale yellow and could completely disintegrated in the 30 s. It could meet the requirements of rapidly disintegrating fully. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles loaded in oral fast dissolving film were (43.36 +/- 2.12)%, (108.82 +/- 5.2) nm, (-34.18 +/- 1.07) mV, 0.088 +/- 0.012, respectively. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles in solution were (41.26 +/- 2.22)%, (181.82 +/- 4.48) nm, (-30.67 +/- 0.81) mV, 0.092 +/- 0.012, respectively. The difference of pharmacodynamics among film of cucurbitacin B-loaded micelles, cucurbitacin B-loaded micelles and free cucurbitacin B in vivo was compared. Solubility of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles has also been greatly improved. The tumor inhibition rate of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles was significantly improved and did not change significantly before and after solidified. These showed that the sodium deoxycholate/phospholipid-mixed micelles could enhance the antitumor activities of cucurbitacin B and the stability of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles was improved significantly after solidified by oral fast dissolving film technology without pharmacodynamic properties changed significantly.
Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; Cell Line, Tumor ; Deoxycholic Acid ; chemistry ; Drug Carriers ; chemistry ; Humans ; Male ; Mice ; Neoplasms ; drug therapy ; Phospholipids ; chemistry ; Solubility ; Triterpenes ; administration & dosage ; chemistry

Objective To investigate the expression and distribution of the downstream substrate of extracellular regulated protein kinase(ERK1/2) pathway, ternary complex factor phospho-Elk-1, in rat brains with chronic fluorosis, and reveal the mechanism of the impaired learning and memory ability caused by chronic fluorosis. Methods Seventy-two SD rats, weighing 100 - 120 g, were randomly divided into 3 groups, 24 in each group (half male and half female). The rats in control group were fed with tap water (fluoride < 0.5 mg/L); low- and high-dose fluoride groups were fed with tap water with different concentrations of NaF(5.0,50.0 mg/L F-, respectively). After 6 months, body weight was weighed, dental fluorosis was determined by observation and urinary fluoride and bone fluoride were detected by fluorine ion-selective electrode; the learning ability of rats was measured by navigation test of Morris water maze, and memory ability by spatial probe test in Morris water maze; the expression and distribution of phospho-Elk-1 in different brain regions were detected by immunohistochemistry method. Results In low- and high-fluoride groups, the body weight of rat[(449.2 ± 77.1), (312.8 ± 89.7)g] was significantly decreased than that of control [(635.5 ± 76.2 )g, all P< 0.05], the varying degrees of dental fluorosis were observed(x2 = 7.83, P<0.05), urinary fluoride[(2.56 ±0.91),(5.73 ±3.14)mg/L] and bone fluoride[(709.2 ± 37.4) ,(1306.3 ± 102.4) mg/kg] were significantly higher than those in controls[(0.92 ± 0.30)mg/L,(348.5 ± 89.2)mg/kg, all P< 0.05]. The escape latency of low- and high-fluoride groups[ (7.4 ± 4.1), (12.2 ± 5.7)s] was longer than that of control [(4.8 ± 2.7 )s, all P < 0.05] and the escape latency in high-fluoride group was significantly longer than that in other groups (all P < 0.05); in spatial probe test, the time of first crossing platform was longer in rats with fluorosis [(4.18 ± 1.10),(5.89 ± 0.56)s] as compared to control[(1.17 ± 0.75)s, all P< 0.05]. Expressions of phospho-Elk-1 in the hippocampus CA1(167.4 ± 8.3,163.2 ± 9.4), CA2(175.7 ± 5.0,183.3 ± 4.2), CA3(165.2 ± 11.6,162.9 ± 4.4), CA4(168.7± 6.9,169.5 ±5.3), fascia dentate (185.2 ±4.0,193.1 ±6.1) and caudate putamen( 181.4 ± 3.8, 179.8 ± 5.5) in low- and high-fluoride groups were higher than those of controls(142.4 ± 8.1,144.9 ± 8.4,143.6 ± 5.8, 116.8 ± 9.1,140.2 ± 7.8,163.1 ± 13.1, all P< 0.05). Conclusion Chronic fluorosis can cause increased expression of phospho-Elk-1 in the hippocampus and caudate putamen region of rat brains, which might be related to the mechanisms of decreased learning and memory ability of rats overexposed to fluoride.

Arachidonic acid is an essential fatty acid in human nutrition and a biogenetic precursor of the biologically active prostaglandins and leukotrienes. ?~5 desaturase catalyzes the ?~5 dehydrogenation of di-homo-?-linolenic acid to form arachidonic acid in biosynthetic pathway of arachidonic acid. Using real time PCR technology,the transcriptional expression levels of gene encoding ?5 desaturase in three Mortierella alpina strains M10,M6 and M23,and in different growth phase of high arachidonic acid yielding strain M6,were determined. Results showed that there was a distinct corelationship between mRNA transcript level of ?~5 desaturase gene and biosynthesis of arachidonic acid. Results indicated that ?~5 desaturase plays an important role in arachidonic acid biosynthesis.

Objective: To explore the potential mechanisms of gastric cancer (GC), long noncoding RNA (lncRNA) and mRNA expression profiling of 3 paired GC fresh tissues and their matched adjacent non-cancerous tissues was detected through microarray analysis. Methods: The functions of differentially expressed lncRNA and mRNA were recognized by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The co-expression network was constructed to find the relevance with corresponding mRNA by using hypergeometric cumulative distribution function of MATLAB 2012b and Cytoscape software. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of 5 differentially expressed key lncRNAs, which were selected in 30 paired GC fresh tissues. Results: Compared with normal tissues, 1 499 lncRNAs and 6 002 mRNAs were dysregulated in GC tissues. The qRT-PCR results showed that the 5 key lncRNAs were consistent with those from the microarray data. Cis-regulatory gene analyses showed the chromosome location of these key lncRNAs, and revealed the associated co-expressed genes. The trans-analyses results demonstrated that enormous transcription factors regulated lncRNA and gene expression. Conclusion: These differentially expressed lncRNAs in GC may be promising biomarkers and provide valuable information for GC targeted treatment.

OBJECTIVEOver the last few decades, diabetic cardiomyopathy has been identified as a significant contributor in cardiac morbidity. However, the mechanisms of diabetic cardiomyopathy have not been clarified.

METHODSIn the present study, a diabetic rat model was induced by the intraperitoneal injection of streptozotocin. The myocardial CD147 expression and extent of glycosylation, as well as thematrixmetalloproteinases(MMPs) expression and activity, were observed in the diabetic and synchronous rats.

RESULTSThe results showed that CD147 located on sarcolemma of cardiomyocytes. The myocardial CD147 expression and glycosylation were significantly increased in the diabetic rats as compared with the control. Expression of MMP-2 protein, MMP-2 and MMP-9 activity were also increased in left ventricular myocardium in the diabetic rats. Tamoxifen only inhibited the enhanced expression of myocardial CD147 in the diabetic rats, but not in synchronous control rats. Tamoxifen inhibited glycosylation of myocardial CD147 in both diabetic and control rats. The inhibition of tamoxifen on CD147 glycosylation was stronger than on the expression in the myocardium. The extent of myocardial CD147glycosylation was positively related toMMP-2 and MMP-9 activity. Tamoxifen induced an inhibition of myocardial MMP-2 and MMP-9 activity in the control and diabetic rats.

CONCLUSIONThese results indicate that myocardial CD147 expression, especially the extent of glycosylation, regulates MMP-2 and MMP-9 activity, then accelerates cardiac pathological remodeling inducing diabetic cardiomyopathy. Tamoxifen inhibits myocardial CD147 glycosylation and further depress the activity of MMPs. Therefore, tamoxifen may protect the diabetic rats against diabetic myocardium.

Animals ; Basigin ; metabolism ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; drug therapy ; Glycosylation ; Heart ; drug effects ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Myocardium ; metabolism ; Myocytes, Cardiac ; cytology ; Rats ; Sarcolemma ; metabolism ; Tamoxifen ; pharmacology

OBJECTIVETo observe effect of acupuncture on asthma at acute stage.

METHODSNinety cases of asthma at acute stage were randomly divided into an observation group of 60 cases and a control group of 30 cases. Clinical therapeutic effect and the mechanisms were studied from symptoms and signs, pulmonary function and serum interleukin -4 (IL-4), gamma-interferon (INF-gamma).

RESULTSThe pulmonary function was improved, the vital capacity was increased and attack of asthma was reduced in both the observation group and the control group, but the observation group was better than the control group in the pulmonary function improving degree (P < 0.05).

CONCLUSIONAcupuncture can strengthen the relieving action of medicine on asthma and it is one of effective methods for bronchial asthma.

Acupuncture Therapy ; Asthma ; therapy ; Humans ; Interferon-gamma ; blood ; Lung ; Vital Capacity

OBJECTIVETo investigate the effects of non-neuronal muscarinic receptors (NNMR) stimulation on atherosclerosis and endothelial cells activation.

METHODSAtherosclerosis model was established in ApoE-/- mice by a high fat diet for 7 weeks. During the experimental periods, animals were received a low (7 mg/kg/d) or a high (21 mg/kg/d) dose of arecoline by gavage. At the termination of the treatments, serum total cholesterol and NO levels were measured, and the aorta morphology was analyzed by hematoxylin and eosin staining. The gene expression of monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in the thoracic aortas was determined by RT-PCR, and the MCP-1 protein expression and NF-κB activity were detected by Western blot analysis. NO production, MCP-1 secretion in cultured rat aortic endothelial cells (RAECs), and monocyte-endothelium adhesion assay were also performed after arecoline treatments.

RESULTSArecoline efficiently decreased atherosclerotic plaque areas, increased serum nitric oxide (NO) content, suppressed the mRNA and protein expression of MCP-1, and modulated the IκB-α degradation and P65 phosphorylation in the aortae of ApoE-/- mice. Furthermore, arecoline promoted NO production and suppressed MCP-1 secretion in cultured RAECs after ox-LDL exposure, and either atropine or NG-nitro-L-arginine methylester could abrogate these effects. Arecoline also significantly inhibited the adherence of U937 monocytes to the ox-LDL injured human umbilical vein endothelial cells, which could be abolished by atropine.

CONCLUSIONOur results indicate that arecoline attenuates the progression of atherosclerosis and inhibits endothelial cells activation and adherence by stimulating endothelial NNMR. These effects, at least in part, are due to its modulation on NF-κB activity.

Animals ; Aorta ; cytology ; Apolipoproteins E ; Arecoline ; pharmacology ; Atherosclerosis ; physiopathology ; prevention & control ; Cell Adhesion Molecules ; metabolism ; Chemokine CCL2 ; metabolism ; Cholesterol ; blood ; Disease Progression ; Endothelial Cells ; cytology ; drug effects ; Endothelium, Vascular ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; I-kappa B Proteins ; metabolism ; Lipoproteins, LDL ; Mice ; Mice, Knockout ; Monocytes ; cytology ; NF-KappaB Inhibitor alpha ; Nitric Oxide ; blood ; Nitroarginine ; pharmacology ; Rats ; Receptors, Muscarinic ; physiology ; Transcription Factor RelA ; metabolism