DMSO-soluble cigarette smoke particles alter the expression of endothelin B receptor in rat coronary artery.

In coronary artery diseases, cigarette smoking is a risk factor and the endothelin system plays a key role in the pathogenesis. This study was to examine if dimethylsulfoxide-soluble smoke particles (DSP) upregulate endothelin type-B (ETB) receptors in the coronary artery and investigate the mechanism. The isolated rat coronary arteries were organ-cultured for 24 h. The contractile response of the coronary artery was recorded by myograph. The mRNA and protein expression of the ETB receptors was studied using quantitative real-time PCR and immunohistochemistry. Results showed that the ETB receptor agonist, sarafotoxin 6c, induced a weak contraction in the fresh coronary artery. After culture, the contraction curve mediated by ETB receptor was shifted towards the left with an increased Emax of 152 ± 12%. DSP of 0.2 and 0.4 µl/ml shifted the concentration-contractile curves towards the left with further increased Emax of 270 ± 26 and 280 ± 29%, respectively. The culture increased ETB receptor mRNA and protein levels from fresh arteries, which was further enhanced by DSP. PD98059 (ERK1/2 inhibitor), wedelolactone (NF-κB inhibitor), actinomycin D or cycloheximide significantly inhibited the DSP-enhanced contraction and expression of mRNA and protein of the ETB receptor. However, SB203580 (p38 inhibitor) further increased DSP-enhanced contraction and protein expression of the ETB receptor. The results indicate that DSP upregulates ETB receptors in rat coronary artery via ERK1/2 and the NF-κB pathway.

Serum irisin associates with breast cancer to spinal metastasis.

The aim of this study was to determine whether the serum level of irisin can be a candidate to predict the spinal metastasis in patients with breast cancer.In a cross-sectional study, 148 patients were recruited. Of those, 53 (35.8%) had spinal metastasis. The baseline characteristics were compared by status of spinal metastasis. Multiple logistic regression analysis was used to determine whether the serum irisin can be a candidate for predicting breast cancer to spinal metastasis. The correlation coefficient analysis was used to confirm the correlation between the serum irisin and lipid metabolic parameters and body mass index (BMI), respectively.The serum irisin was higher in patients without spinal metastasis (7.60 ±â€Š3.80). Multivariable analysis showed that the serum irisin was protective to the presence of spinal metastasis in patients with breast cancer after adjustments of age and BMI (odds ratio, 0.873; 95% confidence interval, 0.764-0.999). Furthermore, there was a positive correlation between the serum irisin and BMI (r = 0.263). The patients with metabolisc syndrome (MetS) had a higher level in serum irisin. In addition, the higher numbers of MetS components were associated with higher serum irisin.Higher serum irisin can be a protective factor of spinal metastasis in patients with breast cancer. The BMI is positively associated with the serum level of irisin. Furthermore, patients with MetS tended to have a higher level of serum irisin.

Antihypertensive effect of formononetin through regulating the expressions of eNOS, 5-HT2A/1B receptors and α1-adrenoceptors in spontaneously rat arteries.

One of the main pathological changes of hypertension is the dysfunction of blood vessels. We have found in our previous study that formononetin, one kind of phytoestrogens, has an acute antihypertensive effect. Therefore, we hypothesized that formononetin might produce a chronic antihypertensive effect through regulating the expressions of contractile receptors and endothelial nitric oxide synthase (eNOS) in artery. The present study was conducted to verify this effect. Male spontaneously hypertensive rats (SHRs) were divided into two groups, orally administrated formononetin (50mg/kg per day) and Tween 80 vehicle, respectively, for 8 weeks. The blood pressure was measured by tail-cuff method. Isometric tension of arterial rings was recorded by a myograph system. The mRNA and protein expression in arteries was determined with quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Results showed that the systolic blood pressure of SHRs decreased significantly in formononetin group compared to Tween 80 group. The vasoconstriction induced by phenylephrine or 5-hydroxytryptamine (5-HT) in the mesenteric artery segments in formononetin group was decreased, and the relaxation induced by acetylcholine was increased compared with that in Tween 80 group. In the mesenteric arteries of the formononetin-treated SHRs, the expressions of α(1)-adrenoceptors and 5-HT(2A/1B) receptors at both mRNA and protein levels decreased, while the mRNA and protein expressions of eNOS increased. In conclusion, formononetin has a chronic antihypertensive effect in SHRs. The antihypertensive mechanism may be associated with the down-regulation of α(1)-adrenoceptors and 5-HT(2A/1B) receptors, and the up-regulation of eNOS expression in arteries.

Compatibility of olfactory ensheathing cells with functionalized self-assembling peptide scaffold in vitro.

BACKGROUND: Olfactory ensheathing cell (OEC) transplantation is a promising or potential therapy for spinal cord injury (SCI). However, the effects of injecting OECs directly into SCI site have been limited and unsatisfied due to the complexity of SCI. To improve the outcome, proper biomaterials are thought to be helpful since these materials would allow the cells to grow three-dimensionally and guide cell migration. METHODS: In this study, we made a new peptide hydrogel scaffold named GRGDSPmx by mixing the pure RADA16 and designer peptide RADA16-GRGDSP solution, and we examined the molecular integration of the mixed nanofiber scaffolds using atomic force microscopy. In addition, we have studied the behavior of OECs in GRGDSPmx condition as well as on RADA16 scaffold by analyzing their phenotypes including cell proliferation, apoptosis, survival, and morphology. RESULTS: The experimental results showed that GRGDSPmx could be self-assembled to form a hydrogel. Inverted optical microscopic and scanning electron microscopic analyses showed that OECs are viable and they proliferate within the nanostructured environment of the scaffold. Thiazolyl blue (MTT) assay demonstrated that OEC proliferation rate was increased on GRGDSPmx scaffold compared with the pure RADA16 scaffold. In addition, OECs on GRGDSPmx scaffolds also showed less apoptosis and maintained the original spindle-shaped morphology. Calcein-AM/PI fluorescence staining revealed that OECs cultured on GRGDSPmx grew well and the viable cell count was 95%. CONCLUSION: These results suggested that this new hydrogel scaffold provided an ideal substrate for OEC three-dimensional culture and suggested its further application for SCI repair.

A facile method for the synthesis of partially O-methylated alditol acetate standards for GC-MS analysis of galactofuranose-containing structures.

Mixtures of partially O-methylated alditol acetate standards of galactofuranose were synthesized rapidly. Methyl galactofuranosides were obtained with a yield of 79.9% within 4h under optimized reaction conditions. Methylation of methyl glycosides was carried out in the presence of BaO/Ba(OH)2·8H2O, giving rise to mixtures of partially methylated glycosides. The batch containing the most diverse structures of methyl ethers was converted into partially O-methylated alditol acetates (PMAAs) and then subjected to GC-MS. These PMAAs could be used as GC-MS standards for simultaneous identification of galactofuranose units with diverse linkages in complex carbohydrates.

Lipid soluble smoke particles upregulate endothelin receptors in rat basilar artery.

The present study examines the effect of dimethylsulphoxide-soluble particles (DSP) from cigarette smoke on endothelin (ET) receptors in the basilar artery. The contractile responses to ET-1 (ET(A) and ET(B) receptors agonist) and sarafotoxin 6c (ET(B) receptor agonist) were studied using a sensitive myograph. The mRNA levels of ET receptors were determined with real-time PCR, while the protein level was evaluated by immunohistochemistry. The results showed that a DSP concentration of 0.4 microl/ml increased the contractile responses induced by sarafotoxin 6c and ET-1 and the mRNA and protein levels of the ET receptors. Inhibitor SB203580 (a p38 inhibitor), staurosporine (a PKC inhibitor) or wedelolactone (a NF-kappaB inhibitor) attenuated the elevated sarafotoxin 6c-induced contraction, the increased mRNA expression and protein levels of the ET(B) receptor induced by DSP. The effects on the ET(A) receptor induced by DSP 0.4 microl/ml were inhibited by co-incubation with PD98059 (an ERK1/2 inhibitor) or SP600125 (a JNK inhibitor) and were further enhanced by SB203580. The results indicate that DSP 0.4 microl/ml upregulates the ET(B) receptor of basilar arterial smooth muscle cells via activation of the p38 pathway and transcriptional factor NF-kappaB, while also upregulating the ET(A) receptor via activation of the ERK1/2 and JNK pathways. Additionally, the p38 pathway seems to be involved in the feedback regulation of the ET(A) receptor.