Animals ; Arrestins ; metabolism ; Hypoxia ; metabolism ; Male ; Prefrontal Cortex ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism ; beta-Arrestin 1 ; beta-Arrestins

Objective Overexpressions of epidermal growth factor(EGF)and EGF receptor have been associ- ated with progression and invasive phenotype of pancreatic cancer.However,the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood.In this study,effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated.Methods The effects of EGF on the proliferation,adhesion and invasion of pancreatic cancer cells were detected by WST-1 prolif- eration assay,adhesion assay and invasive assay,respectively.The activity and expression of MMP-2 and MMP-9 were examined by zymography,Western blot and RT-PCR,respectively.The activity of NF-?B was examined by EMSA.Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion.The expressions of NF-?B and MMP-9 were significantly increased by EGF,but EGF did not affect the activity and expression of MMP-2.Furthermore,EGF stimulated the NF-?B binding activity.Pre- treatment with NF-?B inhibitors,pyrrolidine dithiocarbamate(PDTC),could significantly inhibit the activity of NF-?B induced by EGF.Meanwhile,the EGF-induced expression and activity of MMP-9,as well as cell invasiveness were also inhibited by NF-?B inhibitor.Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF-?B in pancreatic cancer cells,which implies that NF-?B inhibitant,such as PDTC,may diminish the invasiveness of pancreatic cancer cells.

[ ABSTRACT] Interstitial cells of Cajal ( ICC) is the pacemaker in the gastrointestinal tract , which is closely as-sociated with the formation of slow wave and the regulation of gastrointestinal motility .As the pacemaker of gastrointestinal tract, the activation of pacing signal is triggered by the local calcium oscillation in the ICC .The change of calcium concen-tration can activate many relevant ion channels , such as NSCC, ANO1, VGCC, HCN channels and potassium channels , which can generate a large number of pacing current to form the slow wave and then propagated by the gap junction between the ICC networks and smooth muscle cells to make the peristalsis of gastrointestinal tract in autonomic rhythm .However, the mechanism of these ion channels in the pacemaker activity is still unclear , so we refer to make a review about the re-search progress on these pacemaker channels in this article to illuminate the mechanism of pacemaker activity in ICC .

HIF-1 is composed of HIF-1α and HIF-1β subunits. It promotes target genes transcription under hypoxia and plays essential roles in cell development, physiological adaptations, and pathological processes. In the past 10 years, the research on signaling pathways of HIF-1 in response to cell hypoxia stress, especially on HIF-1α-mediated gene transcription has made great progress.
Animals ; Cell Hypoxia ; physiology ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Signal Transduction

Asian Continental Ancestry Group ; genetics ; Carnitine Acyltransferases ; deficiency ; genetics ; China ; Founder Effect ; Humans ; Infant, Newborn ; Male ; Mutation ; Sudden Infant Death ; genetics

OBJECTIVETo analysis the risk factors of pancreatic fistula after pancreaticoduodenectomy (PD).

METHODSA retrospective clinical study had been done in 97 patients who underwent PD between June 2001 and June 2006. The two groups were first compared by the univariate analysis;logistic regression was then used to determine the effect of multiple factors on pancreatic fistula. A P-value of less than 0.05 was considered to be statistically significant.

RESULTSOf the 97 patients, 13 patients were identified as having pancreatic fistula. Factors significantly increasing the risk of pancreatic fistula by univariate analysis included preoperative serum total bilirubin (P = 0.038), operative time (P = 0.003) and whether or not Braun anastomosis (P = 0.034), and prophylactic use of somatostatin (P = 0.003) after operation. A multivariate logistic regression analysis revealed the factors most highly associated with pancreatic fistula to be preoperative serum total bilirubin (OR = 11.687, P = 0.021) and postoperative prophylactic use of somatostatin (OR = 0.056, P = 0.020).

CONCLUSIONSPreoperative serum total bilirubin more than 170 mmol/L was a risk factor of pancreatic fistula after PD, and postoperative prophylactic use of somatostatin was a protect factor of pancreatic fistula after PD.

Adult ; Aged ; Bilirubin ; blood ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Fistula ; etiology ; Pancreaticoduodenectomy ; adverse effects ; Postoperative Complications ; etiology ; Retrospective Studies ; Risk Factors ; Somatostatin ; therapeutic use ; Young Adult

OBJECTIVETo clarify the clinicopathologic significance of the expression of the Bcl-2 protein (pBcl-2) and the Bax protein (pBax), and their clinical implications in Chinese and Japanese patients with human invasive ductal carcinomas (IDCs) of the pancreas.

METHODSThe study included 59 Chinese and 65 Japanese patients with IDCs of the pancreas. pBcl-2 and pBax expression were immuno-stained with streptavidin-biotin (SAB) method.

RESULTSpBcl-2 (+) was seen in 35.6% of Chinese and in 23.1% of Japanese patients. pBax (+) was seen in 49.2% of Chinese and 64.7% of Japanese patients. A comparison between them showed that there were significant differences in the male patients, in the patients with the moderately differentiated cancer, and in the elderly patients (chi squared = 4.447, P = 0.035; chi squared = 4.114, P = 0.043; chi squared = 6.657, P = 0.010 respective). In both Chinese and Japanese patients, those with pBcl-2 positive expression had a significantly higher survival rate than those with negative one (chi squared = 9.99, P = 0.0016; chi squared = 7.63, P = 0.0058). The group with pBax positive expression had a significantly higher survival rate in Japanese patients (chi squared = 9.37, P = 0.0022). Japanese patients whose tumors exhibited pBcl-2 and pBax positive immunostaining survived significantly longer than Chinese patients did (chi squared = 4.48, P = 0.0342; chi squared = 5.23, P = 0.023).

CONCLUSIONSThe expressions of both pBcl-2 and pBax are high found in Chinese and Japanese patients. The pBcl-2 positive expression implies a better prognosis in both Chinese and Japanese patients with IDCs of the pancreas. The effect of pBax expression on prognosis is different between Chinese and Japanese patients.

Adult ; Aged ; Carcinoma, Pancreatic Ductal ; metabolism ; China ; Female ; Humans ; Immunohistochemistry ; Japan ; Male ; Middle Aged ; Pancreatic Neoplasms ; ethnology ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; bcl-2-Associated X Protein ; biosynthesis

OBJECTIVETo investigate the effect of Rongshi granule on osteopontin(OPN) expression.

METHODThe urlisthiasis rats were induced by ethylene glycol (EG) and ammonium chloride, the control group rats were non-treated, and the Rongshi granule groups (low-dose group, middle-dose group and high-dose group) were administered Rongshi granule in addition to EG and ammonium chloride in 21 days. Pooled 24 h urine samples from each group were collected weekly with the use of metabolic cages, the concentration of uric calcium and oxalic acid were respectively measured by EDTA and photoelectric colorimetric method. Eight animals from each group were killed at 0, 7, 14, and 21 days, kidneys were histologic examinaed and immunohistochemical staining.

RESULTThe expression of kidney osteopontin in model group was obviously higher than that of control group (P <0.01), and was up to the highest at 21 days with 1.4 times (0.281 3/0.201 8) of the control group. The expression of kidney osteopontin in all of the Rongshi granule groups were lower than those of model group (P < 0.05), with an obvious dose-dependent manner. The degree of the kidney calcium oxalate crystal of the rats in all the Rongshi granule groups was much lower than that of model group, and the uric calcium and oxalic acid were much lower than those of model group (P < 0.01).

CONCLUSIONThe Rongshi granule could inhibit the expression of osteopontin in rat urolithiasis model.

Ammonium Chloride ; Animals ; Calcium ; urine ; Calcium Oxalate ; metabolism ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Ethylene Glycol ; Female ; Kidney ; metabolism ; Kidney Calculi ; chemically induced ; metabolism ; Male ; Osteopontin ; metabolism ; Oxalic Acid ; urine ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

High-altitude hypoxia can induce physiological dysfunction and mountain sickness, but the underlying mechanism is not fully understood. Corticotrophin-releasing factor (CRF) and CRF type-i receptors (CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal (HPA) axis and modulators of endocrine and behavioral activity in response to various stressors. We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time- and dose-dependent manner, impaired or improved learning and memory, and anxiety-like behavioral change. Meanwhile, hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems, including suppression of growth and development, as well as inhibition of reproductive, metabolic and immune functions. In contrast, the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitude-hypoxia challenge, suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interactions between the genes and environment. All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction. This review extends these findings.
Altitude ; Animals ; Brain ; physiopathology ; Corticotropin-Releasing Hormone ; metabolism ; Hypothalamo-Hypophyseal System ; physiopathology ; Hypoxia ; physiopathology ; Pituitary-Adrenal System ; physiopathology ; Receptors, Corticotropin-Releasing Hormone ; metabolism ; Tibet

OBJECTIVETo investigate the role of autophagy inhibitor chloroquine (CQ) in the proliferation of pulmonary arterial smooth muscle cells (PASMCs) in hypoxia conditions.

METHODSThe following groups in this study were set up: control group, hypoxia group, 50 micromol/L CQ + hypoxia group, 50 micromol/L CQ group. The viability of PASMCs in every group was detected by MTT assay. Autophagic vacuoles in the cells were observed by MDC staining. Protein expression of microtubule associated protein light chain 3 (LC3) was measured by Western blot. Migration of PASMCs was detected by wound healing assay.

RESULTSCompared with control group, no effect on the viability of PASMCs was observed treated by CQ alone. In 1% hypoxia group, cell viability increased significantly compared with that in control group. The number of autophagic vacuoles and the rate of cell migration and also protein expression of LC3-II were also markedly increased. Compared with hypoxia group, addition of CQ increased the number of autophagic vacuoles and the levels of LC3-II protein, but decreased the proliferation and migration of PASMCs.

CONCLUSIONHypoxia could activates autophagy and contributes to proliferation and migration of PASMCs, and autophagy inhibitor CQ could decrease the effect of hypoxia on PASMCs through inhibiting autophagy process.

Autophagy ; drug effects ; Cell Hypoxia ; Cell Movement ; Cell Survival ; Cells, Cultured ; Chloroquine ; pharmacology ; Humans ; Microtubule-Associated Proteins ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; Pulmonary Artery ; cytology