No abstract

1 Stimulation of bradykinin (BK) receptors coupled to phosphoinositide (PI) hydrolysis was investigated in canine cultured tracheal smooth muscle cells (TSMCs). BK, kallidin, and des-Arg9-BK, stimulated [3H]-inositol phosphates (IPs) accumulation in a dose-dependent manner with half-maximal responses (ECm) at 20 ± 5, 13 ± 4, and 2.3 ± 0.7 nM, (n = 5), respectively. 3 Short-term exposure of TSMCs to phorbol 12-myristate 13-acetate (PMA, 1 1M), attenuated BKstimulated IPs accumulation. The concentrations of PMA that gave half-maximal and maximal inhibition of BK-induced IPs accumulation were 15 ± 4 nM and 1 fLM, n = 3, respectively. The inhibitory effect of PMA on BK-induced response was reversed by staurosporine, a protein kinase C (PKC) inhibitor, suggesting that the inhibitory effect of PMA was mediated through the activation of PKC. 4 Prolonged incubation of TSMCs with PMA for 24 h, resulted in a recovery of receptor responsiveness which may be due to down-regulation of PKC. The inactive phorbol ester, 4oc-phorbol 12, 13-didecanoate at 1 tlM, did not inhibit this response. 5 The site of this inhibition was further investigated by examining the effect of PMA on AIF4--induced IPs accumulation in canine TSMCs. A1F4 -stimulated IPs accumulation was inhibited by PMA treatment, suggesting that the G protein(s) can be directly activated by A1F4-, which is uncoupled from phospholipase C by PMA treatment. 6 Incubation of TSMCs in the absence of external Ca2+ or upon removal of Ca2+ by addition of EGTA, caused a decrease in IPs accumulation without changing the basal levels. Addition of Ca2" (3-620 nM) to digitonin-permeabilized TSMCs stimulated IPs accumulation was obtained by inclusion of either guanosine 5'-O-(3-thiotriphosphate) (GTPyS) or BK. The combination of GTPyS and BK caused an additive effect on IPs accumulation. 7 Pretreatment of TSMCs with cholera toxin enhanced BK-stimulated IPs accumulation, whereas there was no effect with pertussis toxin. 8 These data suggest that BK-stimulated PI metabolism is mediated by the activation of BK B2 receptors coupling to a G protein which is not blocked by cholera toxin or pertussis toxin treatment and dependent on external Ca2". The transduction mechanism of BK coupled to PI hydrolysis is sensitive to feedback regulation by PKC.

1 The relationship between muscarinic receptor-mediated phosphatidylinositol 4, breakdown and the increase of intracellular Ca2+ ([Ca2+])i has been examined in canine cultured tracheal smooth muscle cells (TSMCs

Liquid biopsies use blood or urine as test samples, which are able to be continuously collected in a non-invasive manner. The analysis of cancer-related biomarkers such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA, and exosomes provides important information in early cancer diagnosis, tumor metastasis detection, and postoperative recurrence monitoring assist with clinical diagnosis. However, low concentrations of some tumor markers, such as CTCs, ctDNA, and microRNA, in the blood limit its applications in clinical detection and analysis. Nanomaterials based on graphene oxide have good physicochemical properties and are now widely used in biomedical detection technologies. These materials have properties including good hydrophilicity, mechanical flexibility, electrical conductivity, biocompatibility, and optical performance. Moreover, utilizing graphene oxide as a biosensor interface has effectively improved the sensitivity and specificity of biosensors for cancer detection. In this review, we discuss various cancer detection technologies regarding graphene oxide and discuss the prospects and challenges of this technology.

Gemcitabine plus cisplatin is an effective, well-tolerated regimen as a first-line treatment for recurrent/metastatic nasopharyngeal carcinoma.