Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new tyrosine kinase inhibitor (denoted as CH331) and its poly(epsilon-caprolactone) (PCL) microspheres were studied. The CH331 particles were pretreated with ethanol and then used to prepare CH331 loaded PCL microspheres by S/O/W solvent evaporation technique. Solubility values of CH331 in several organic and aqueous media were measured. The amount of ethanol and CH331 solubility play a significant role in drug loading, encapsulation efficiency, mean diameter and morphology of the microspheres, crystallinity and in vitro drug release. The treatment with a suitable amount of ethanol leads to more uniform sizes, better appearance and higher encapsulation efficiency for the microspheres. Compared with 0.5% PVA phosphate buffer solution (pH 7.4), 0.5% PVA aqueous solution as outer aqueous phase lowers encapsulation efficiency of microspheres, however, improves the drug release behavior.
...
PMID:Tyrosine kinase inhibitor loaded PCL microspheres prepared by S/O/W technique using ethanol as pretreatment agent. 1904 82

A pluripotent cytokine, leptin, released locally within the mucosal tissue is an important mediator of the processes of gastric mucosal defense and repair. Here, we report that leptin protection of gastric mucosal cells against ethanol cytotoxicity requires epidermal growth factor receptor (EGFR) participation. We show that the protective effect of leptin against ethanol cytotoxicity was associated with the increased EGFR and cPLA(2) phosphorylation, and characterized by a marked increase in arachidonic acid (AA) release and prostaglandin (PGE(2)) generation. The loss in countering capacity of leptin on the ethanol-induced cytotoxicity was attained with Src kinase inhibitor, PP2, and EGFR kinase inhibitor, AG1478, as well as ERK inhibitor, PD98059. Moreover, all three agents evoked also the inhibition in leptin-induced upregulation in cPLA(2) activity, AA release, and PGE(2) generation. Furthermore, changes caused by leptin in EGFR phosphorylation and cPLA(2) activation were susceptible to suppression by GM6001, a metalloprotease inhibitor of membrane-anchored EGFR ligand cleavage. These findings disclose an important link between leptin-induced and Src kinase-mediated EGFR transactivation and the activation of cytosolic phospholipase A(2) that leads to up-regulation in PGE2 production, thus providing new insights into the mechanism of gastric mucosal protection by leptin.
...
PMID:Leptin-induced cytosolic phospholipase A2 activation in gastric mucosal protection against ethanol cytotoxicity involves epidermal growth factor receptor transactivation. 1912 49

Oxysterols are a family of 27-carbon cholesterol oxidation derivatives that may be absorbed with the diet or originated endogenously. These cholesterol metabolites are now considered to be potentially involved in the initiation and progression of major chronic diseases including atherosclerosis, neurodegenerative processes, diabetes, kidney failure, and ethanol intoxication. Thus we deemed it of interest to comprehensively analyze the actual relevance of oxysterols, acting through up-regulation of inflammation, apoptosis and fibrosis, to human pathology from cell signaling to disease expression; we also review the available literature on related therapeutic prospects. Oxysterols of pathophysiologic relevance generally possess a strong pro-oxidant effect, chiefly since they activate NAD(P)H oxidases. Further, stimulation of the MEK/ERK signaling pathway appears to be a common feature of the biochemical effects of this class of compounds. Selective metabolic inhibitors of NAD(P)H oxidase and the MAPK pathway might quench or even prevent the cytotoxic effects of pathological accumulation of cholesterol oxides in cells and tissues. The marked reduction of plasma oxysterols reported for statin-based therapy is interesting: it has been associated with a lower incidence and prevalence of Alzheimer's disease (AD) and vascular dementia. Quenching reactive oxygen species' generation seems the likely mechanism exploited by statins against AD incidence and development; intervention with antioxidants might thus also be re-considered as regards molecular "integrated" prevention and possible therapy of human "multifactorial" disease processes.
...
PMID:Cholesterol oxidation products and disease: an emerging topic of interest in medicinal chemistry. 1919 32

Fine needle aspiration (FNA) is a rapid tool for detection of breast carcinomas. Evaluation of estrogen and progesterone receptors (ER, PR) and HER2 expression by immunohistochemistry (IHC) are routinely performed in breast carcinomas. Formalin fixation of tissue for a minimum of 6 hours, and for HER2 not more than 48 hours is the current recommended practice. In this retrospective study, we compared ER, PR and HER2 expression in breast carcinomas using archival ethanol-fixed FNA cell block with formalin fixed resection tissue block preparations. 34 archival breast carcinoma FNA cell blocks of primary origin with subsequent resection tissue blocks were identified retrospectively. All 34 cases were diagnosed as invasive ductal carcinoma. Cases with neoadjuvant or adjuvant chemotherapy were excluded. Cell blocks were initially fixed in 50% ethanol (4-12 hrs), followed by formalin fixation (minimum 6 hrs). Tissue blocks were formalin-fixed within 4-8 hrs for 6-48 hrs. ER, PR, and HER2 IHC results on the cell blocks and tissue blocks were compared. Alcohol fixed cell block samples for detection of ER and PR by IHC show good agreement with tissue block samples and are therefore a reliable method (weighted Kappa of 0.773 and 0.785, respectively) to triage patients for hormonal treatment. However, HER2 results show only moderate agreement with a weighted kappa of 0.571. The increase in discrepant results may be due to ethanol fixation which results in false positive increased HER2 expression. These results demonstrate the importance of adherence to the College of American Pathologists/ASCO guidelines for HER2 IHC.
...
PMID:Immunohistochemical detection of estrogen and progesterone receptor and HER2 expression in breast carcinomas: comparison of cell block and tissue block preparations. 1929 6

Complementary and alternative medicine, Cinnamomum cassia is one of the medicinal plants that have been used to improve various diseases caused by insufficient blood circulation. However, relatively little work has been carried out on the angiogenic responses of C. cassia and its active compound cinnamic acid (CA), despite its excellent pharmacological action. In this study, we study the effect of the ethanol extract of C. cassia (CCE) and its active compound CA, on angiogenic processes in in vitro and in vivo. In the Matrigel plug assay in vivo, CCE and CA dose dependently increased von Willebrand Factor (vWF) antigen expression, and hemoglobin contents, whose elevation paralleled the onset of angiogenesis and was considered an early indicator of endothelial activation. CCE and CA induced endothelial cells proliferation, migration and tubule-like structure in vitro. The 25-50% increase observed with CCE (at low doses of 1 or 10 ng/ml) in HUVEC and BAEC proliferation was similar to that observed with CA. The migration and tubule-like structure effect were observed with HUVEC and BAEC. However, the effect of CCE, CA and VEGF on cell proliferation, migration and tubule-like structure in HUVEC were bigger than the effect of CCE, CA and VEGF in BAEC. In addition, CCE and CA each induced 2.2-fold and 2.5-fold increases the production of VEGF, the mRNA expression of VEGF and Flk-1/KDR, the receptor involved in proliferation, migration, and tubule-like structure of endothelial cells. These data suggest that CCE and its active compound CA induce angiogenesis in vivo and in vitro, and this pathway is related with VEGF and Flk-1/KDR expression of endothelial cells.
...
PMID:Stimulatory effect of Cinnamomum cassia and cinnamic acid on angiogenesis through up-regulation of VEGF and Flk-1/KDR expression. 1935 42

The pathogenesis of alcoholic liver injury involves interactions of several intracellular signalling pathways in different cell types of the liver. Alcohol-induced sensitization of liver macrophages to portal endotoxin/lipopolysaccharide (LPS) is considered a hallmark of alcoholic liver disease (ALD). Intracellular mechanisms associated with LPS-induced signalling play a crucial role in the initiation and progression of alcoholic liver injury, and are being extensively explored. LPS recognition by Toll-like receptor 4 (TLR4) on macrophages and other cell types in the liver, activation of downstream signalling pathways culminating in activation of transcription factors such as NFkappaB, AP-1 leads to increased inflammatory cytokine production in ALD. In addition, LPS-induced MAPK such as ERK and p38 also contribute to liver injury. The importance of alcohol-induced reactive oxygen species and interactions with TLR pathways in macrophages leading to inflammation is becoming increasingly evident. Collectively, these signalling pathways induce pro- and anti-inflammatory cytokines that play an important role in ALD. In this review we describe the key signalling intermediates leading to alcohol-induced inflammation in alcoholic liver disease.
...
PMID:Signalling pathways in alcohol-induced liver inflammation. 1939 36

NEP effectiveness at a population level depends on several factors, including the number of injection drug users (IDUs) retained, or consistently accessing services. Patterns of retention in the Baltimore Needle Exchange Program (BNEP) from 1994 to 2006 were calculated using enrollment surveys and client records. We used Andersen's Behavioral Model of Health Services Use to frame our examination of factors associated with retention. Client retention was measured in two ways: whether a client returned to the exchange within 12 months of enrollment and how many times a client returned within these 12 months. BNEP clients (N=12,388) were predominantly male (69%), African-American (73%), and >or=age 30 (86%). Nearly two-thirds (64%) of clients returned within 12 months of their first BNEP visit. The median number of return visits per client within 12 months was one (IQR: 0-5). Young age (<30), being married, having an injection drug use history of less than 20 years, and living farther from the BNEP site were characteristics independently associated with both measures of low retention in multivariate analysis. Among younger injectors, geographical proximity was a particularly important predictor of retention. Further insight into the influence of these factors may help in developing programmatic changes that will be effective in increasing retention.
Drug Alcohol Depend 2009 Aug 01
PMID:Utilization patterns and correlates of retention among clients of the needle exchange program in Baltimore, Maryland. 1946 27

The effect of ethanol-gasoline blends on criteria air pollutant emissions was investigated in a four-stroke motorcycle. The ethanol was blended with unleaded gasoline in four percentages (3, 10, 15, and 20% v/v) and controlled at a constant research octane number, RON (95), to accurately represent commercial gasoline. CO, THC, and NOx emissions were evaluated using the Economic Commission for Europe cycle on the chassis dynamometers. The results of the ethanol-gasoline blends were compared to those of commercial unleaded gasoline with methyl tert-butyl ether as the oxygenated additive. In general, the exhaust CO and NOx emissions decreased with increasing oxygen content in fuels. In contrast, ethanol added in the gasoline did not reduce the THC emissions for a constant RON gasoline. The 15% ethanol blend had the highest emission reductions relative to the reference fuel. The high ethanol-gasoline blend ratio (20%) resulted in a less emission reduction than those of low ratio blends (<15%). This may be attributed to the changes in the combustion conditions in the carburetor engine with 20% ethanol addition. Furthermore, the influence of ethanol-gasoline blends on the reduction of exhaust emissions was observed at different driving modes, especially at 15km/h cruising speed for CO and THC and acceleration stages for NOx.
...
PMID:Effects of ethanol-blended gasoline on air pollutant emissions from motorcycle. 1959 41

A pleiotropic hormone, leptin, secreted into saliva by the acinar cells of salivary glands is an important mediator of the processes of oral mucosal defense. Here, we report on the role of epidermal growth factor receptor (EGFR) transactivation in the signaling events that mediate leptin protection of sublingual salivary gland acinar cells against ethanol cytotoxicity. We show that the protective effect of leptin against ethanol cytotoxicity was associated with the increased EGFR protein tyrosine kinase and cytosolic phospholipase A(2) (cPLA(2)) activity, and characterized by a marked increase in matrix metalloproteinase MMP-9 and arachidonic acid (AA) release, and PGE(2) generation. The loss in countering capacity of leptin against ethanol cytotoxicity was attained with JAK inhibitor AG490, Src inhibitor PP2, and EGFR inhibitor AG1478, as well as ERK inhibitor PD98059. Moreover, the agents evoked also the inhibition in leptin-induced up-regulation in cPLA(2) activity, AA release, and PGE(2) generation. The changes caused by leptin in EGFR phosphorylation, MMP-9, and cPLA(2) activation were susceptible to suppression by metalloprotease inhibitor GM6001, but the production of MMP-9 was not affected by EGFR inhibitor AG1478 or PKC inhibitor Ro318220. These findings point to the involvement of MMP-9 in the event of leptin-induced EGFR transactivation that results in the signaling cascade leading to cPLA(2) activation and up-regulation in PGE(2) generation, thus providing new insights into the mechanism of oral mucosal protection against ethanol toxicity.
...
PMID:Role of epidermal growth factor receptor transactivation in the activation of cytosolic phospholipase A(2) in leptin protection of salivary gland acinar cells against ethanol cytotoxicity. 1961 45

To compare the effects of the food toxin 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and estradiol in hormone-responsive MCF-7 cells, the cells were exposed to different concentrations of either PhIP or estradiol. The effect of various culture conditions (e.g. phenol red, FBS, vehicle (DMSO/EtOH) and seeding density) on responses was studied. Cells were continuously grown with steroid-containing or -deprived medium, or switched from steroid-containing to -deprived medium for the experiments to minimize the effect of background estrogenicity. Effects of PhIP and estradiol on cell viability and proliferation were determined by ATP analysis and Ki-67 immunocytochemistry. Expression of estrogen receptor alpha, cell stress markers (p53 and ERK) and estrogen responsive proteins (c-myc and ERK) were immunoblotted. All concentrations of estradiol induced cell proliferation, viability and changes in protein expression, typical for estrogenic responses. PhIP, however, increased viability only at low concentrations and depending on culture conditions. No changes in protein expressions by PhIP were noted, not even when switching cells from steroid-containing to -deprived medium which down-regulated the expression of proteins at basal level. Vehicle affected significantly viability, especially after exposure to PhIP, but not protein expression while medium changes affected both. In conclusion, the effects of PhIP and estradiol in MCF-7 cells are dependent on culture conditions. The detected PhIP-induced changes are weaker compared to those induced by estradiol.
...
PMID:Responses of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in MCF-7 cells are culture condition dependent. 1964 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---