Potassium (K+) ions are critical for the activation and catalytic cycle of the gastric H+,K+-ATPase, resulting in the secretion of hydrochloric acid into the parietal cell canaliculus. As both symptom, severity and es...Potassium (K+) ions are critical for the activation and catalytic cycle of the gastric H+,K+-ATPase, resulting in the secretion of hydrochloric acid into the parietal cell canaliculus. As both symptom, severity and esophageal mucosal damage in gastro-esophageal reflux disease (GERD) are related to the degree of acid exposure, K+ is a logical target for approaches to inhibit acid production.The probable K+ binding site on the gastric H+,K+-ATPase has recently been described and studies are elucidating how K+ activates the enzyme. K+ channels in the apical membrane of the parietal cell are implicated in the recycling of K+ and, to date, three potential K+ channels (KCNQ1, Kir2.1 and Kir4.1) have been identified. The channels represent theoretical sites for agents to control acid secretion but it will be difficult to develop selective blockers. An alternative strategy is to prevent K+ from activating gastric H+,K+-ATPase; the potassiumcompetitive acid blocker (P-CAB) class inhibits acidsecretion by binding at or near the K+ binding site.Ongoing research is further defining the role of K+ in the functioning of the gastric H+,K+-ATPase, as well as determining the clinical utility of agents directed toward this important cation.展开更多
AIM:To investigate the expression and potential prognostic role of vascular endothelial growth factor(VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors(GEP-NETs) . METHODS:Microvessel density(MVD) in ...AIM:To investigate the expression and potential prognostic role of vascular endothelial growth factor(VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors(GEP-NETs) . METHODS:Microvessel density(MVD) in GEP-NETs was evaluated using endoglin and CD31 immunohistochemistry.In addition,tissue levels of endoglin and VEGF were determined in homogenates by ELISA. RESULTS:Endoglin was highly expressed on tumor endothelial cells.CD31 MVD in GEP-NETs was significantly higher compared to endoglin MVD(P<0.01) .Two-tofour-fold higher tissue levels of endoglin and VEGF were seen in tumors compared to associated normal tissue. This increased endoglin tissue expression in tumors was significantly related to tumor size(P<0.01) ,presence of metastases(P=0.04) ,and a more advanced tumor stage(P=0.02) ,whereas expression of VEGF was not. CONCLUSION:We suggest that endoglin is a potential marker to indicate and predict metastases,which might be useful in the post-resection therapeutic approach of patients with GEP-NETs.展开更多
Vanishing bile duct syndromes (VBDS) are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from li...Vanishing bile duct syndromes (VBDS) are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA), a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes. Several potential mechanisms of action of UDCA have been proposed including stimulation of hepatobiliary secretion, inhibition of apoptosis and protection of cholangiocytes against toxic effects of hydrophobic bile acids.展开更多
The levels of somatostatin(SS)in CSF and blood and pancreatic polypeptide(PP)inplasma were measured by radioimmunoassay in 64 patients with acute ischemiccerebrovascular diseases(ICVD),randomly divided into two groups...The levels of somatostatin(SS)in CSF and blood and pancreatic polypeptide(PP)inplasma were measured by radioimmunoassay in 64 patients with acute ischemiccerebrovascular diseases(ICVD),randomly divided into two groups:group 1(n=31,bothelectro-acupuncture and routine treatments given)and group 2(n=33,routine treatment)and 26 non-ICVD patients were used as controls.The points of electro-acupuncture wereQuchi(LI 12),Waiguan(SJ 5)and Huantiao(GB 30)and Zusanli(St 36).After a courseof treatment,the SS levels in plasma and CSF were significantly increased in the patientsof group 1 with good result and their plasma PP level had no significant change.In thepatients with poor result,however,the PP level was significantly decreased.The resultssuggested that electro-acupuncture might play an active role in alleviating the SSmetabolic disturbance in CNS of ICVD patients.展开更多
AIM: To examine the effect of acute infection caused by herpesvirus (pseudorabies virus, PRV) on pancreatic ductal secretion. METHODS: The virulent Ba-DupGreen (BDG) and non- virulent Ka-RREp01acgfp (KEG) gene...AIM: To examine the effect of acute infection caused by herpesvirus (pseudorabies virus, PRV) on pancreatic ductal secretion. METHODS: The virulent Ba-DupGreen (BDG) and non- virulent Ka-RREp01acgfp (KEG) genetically modified strains of PRV were used in this study and both of them contain the gene for green fluorescent protein (GFP). Small intra/ interlobular ducts were infected with BDG virus (10^7 PFU/mL for 6 h) or with KEG virus (10^10 PFU/mL for 6 h), while non-infected ducts were incubated only with the culture media. The ducts were then cultured for a further 18 h. The rate of HCO3 secretion [base efflux -λ(B)] was determined from the buffering capacity of the cells and the initial rate of intracellular acidification (1) after sudden blockage of basolateral base loaders with dihydro-4,4,- diisothiocyanatostilbene-2,2,-disulfonic acid (500 μmol/L) and amiloride (200 μmol/L), and (2) after alkali loading the ducts by exposure to NH4Cl. All the experiments were performed in HCO3-buffered Ringer solution at 37 ℃ (n = 5 ducts for each experimental condition). Viral structural proteins were visualized by immunohistochemistry. Virallyencoded GFP and immunofluorescence signals were recorded by a confocal laser scanning microscope.RESULTS: The BDG virus infected the majority of accessible cells of the duct as judged by the appearance of GFP and viral anUgens in the ductal cells. KEG virus caused a similarly high efficiency of infection. After blockage of basolateral base loaders, BDG infection significantly elevated -λB-) 24 h after the infection, compared to the non-infected group. However, KEG infection did not modify -λB-). After alkali loading the ducts, -λB-) was significantly elevated in the BDG group compared to the control group 24 h after the infection. As we found with the inhibitor stop method, no change was observed in the group KEG compared to the non-infected group. CONCLUSION: Incubation with the BDG or KEG strains of PRV results in an effective infection of ductal epithelial cells. The BDG strain of PRV, which is able to initiate a lytic viral cycle, stimulates HCO3 secretion in guinea pig pancreatic duct by about fourto fivefold, 24 h after the infection. However, the KEG strain of PRV, which can infect, but fails to replicate, has no effect on HCO3 secretion. We suggest that this response of pancreatic ducts to virulent PRV infection may represent a defense mechanism against invasive pathogens to avoid pancreatic injury.展开更多
We report 2 cases of pancreatic endocrine tumors that caused obstruction of the main pancreatic duct(MPD).A 49-year-old asymptomatic man was referred to our institution because dilation of the MPD was revealed by abdo...We report 2 cases of pancreatic endocrine tumors that caused obstruction of the main pancreatic duct(MPD).A 49-year-old asymptomatic man was referred to our institution because dilation of the MPD was revealed by abdominal ultrasonography(US).No tumor was detected by endoscopic ultrasonography,computed tomography(CT),and magnetic resonance imaging(MRI).The diameter of the MPD was > 20 mm at the body,and no dilation was noted at the head.Although malignancy was not confirmed through cytology or imaging,pancreatic cancer was strongly suspected.Pancreaticoduo-denectomy was performed.Pathological and immunohistochemical examination revealed a 5 mm × 3 mm serotonin-positive endocrine tumor.Fibrosis was present around the MPD and seemed to cause stricture.A 32-year-old asymptomatic man had elevated serum amylase,and US demonstrated dilation of the MPD.No tumor was detected by CT and MRI.Pancreatic cancer was suspected due to stricture and dilation of the MPD.Pancreatectomy of middle part of pancreas was performed.Pathological and immunohistochemical examination revealed a serotonin-positive endocrine tumor sized 5 mm × 4 mm.We report 2 cases of serotonin-positive pancreatic endocrine tumors that caused stricture of the MPD in spite of the small size of the tumor.展开更多
AIM: To investigate the effects of taurolithocholate (TLC)on the canalicular motility in isolated rat hepatocyte cou-plets (IRHC).METHODS: TLC was added to IRHC at concentrationsof 10 and 50 μmol/L, respectively. In ...AIM: To investigate the effects of taurolithocholate (TLC)on the canalicular motility in isolated rat hepatocyte cou-plets (IRHC).METHODS: TLC was added to IRHC at concentrationsof 10 and 50 μmol/L, respectively. In each group, fi vetime-lapse movies containing 3 representative bile cana-liculi were taken under phase-contrast microscopy for12 h. The number of bile canalicular contractions andthe intervals between consecutive canalicular contrac-tions were calculated. Furthermore, the effects of TLC onIRHC were examined by transmission electron micros-copy.RESULTS: The bile canalicular contractions were spon-taneous and forceful in the controls. Active vesicularmovement was observed in the pericanalicular region.Immediately after the addition of TLC, the bile canaliculiwere deformed, and canalicular bile was incorporatedinto the vacuoles. The canaliculi were gradually dilated,and canalicular contractions were markedly inhibited byTLC. The vesicular movements became extremely slowin the pericanalicular region. The number of canalicularcontractions significantly decreased in the TLC-treatedgroups, as compared with that in the controls. The timeintervals were prolonged, as the TLC dosage increased,indicating that bile secretion into the canaliculi wasimpaired with TLC. Transmission electron microscopyrevealed the lamellar transformation of the canalicularmembranes in IRHC treated with TLC.CONCLUSION: TLC impairs both the bile canalicularcontractions and the canalicular bile secretion, possiblyby acting directly on the canalicular membranes in TLC-induced cholestasis.展开更多
Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an a...Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT) and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.展开更多
Introduction Neuroendocrine tumor covers a wide range of neoplasms that originate in the neuroendocrine cells which spread throughout the body. Carcinoid tumor,
Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown...Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors(VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells(DCs), macrophages, and lymphocytes further express certain types of VEGF receptors.VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness.This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.展开更多
Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Anti...Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Antioxidants have been used in various studies to improve islet transplantation procedures. The present study reviews the role of oxidative stress and the benefits of antioxidants in islet transplantation procedures. The bibliographical databases Pubmed and Scopus were searched up to November 2008. All relevant human and animal in-vivo and in-vitro studies, which investigated antioxidants on islets, were included. Almost all the tested antioxidants used in the in-vitro studies enhanced islet viability and insulin secretion. Better control of blood glucose after transplantation was the major outcome of antioxidant therapy in all in-vivo studies. The data also indicated that antioxidants improved islet transplantation procedures. Although there is still insuffi cient evidence to draw definitive conclusions about the efficacy of individual supplements, the benefi ts of antioxidants in islet isolation procedures cannot be ignored.展开更多
Structure and function of the digestive system of a bivalve mollusc, Solen grandis, were studied using light microscopy and histochemical methods. The wall of digestive tube consists of four layers: the mucosal epithe...Structure and function of the digestive system of a bivalve mollusc, Solen grandis, were studied using light microscopy and histochemical methods. The wall of digestive tube consists of four layers: the mucosal epithelium, connective tissue, muscular and fibrosa or serosa (only in the portion of rectum) from the inner to the outer. The ciliated columnar epithelial cells, dispersed by cup-shaped mucous cells, rest on a thin base membrane. There are abundant blood spaces in connective tissue layer. The digestive diverticula are composed of multi-branched duct and digestive tubules. The digestive tubules are lined with digestive and basophilic secretory cells, and surrounded by a layer of smooth muscle fibers and connective tissues. Activities of acid and alkaline phosphatases, esterase and lipase are detected in the digestive cells, and the epithelia of stomach and intestine, suggesting that these cells are capable of intracellular digesting of food materials and absorbing.Besides, acid phosphatase and esterase activities are present in the posterior portion of esophagus. Phagocytes are abundant in blood spaces and the lumens of stomach and intestine, containing brown granules derived from the engulfed food materials. The present work indicates that phagocytes play important roles in ingestion and digestion of food materials, which is supported as well by the activities of acid phosphatase, esterase and lipase detected in blood spaces.展开更多
AIM: To investigate the expression and methylation status of the secreted frizzled-related protein 2 (SFRP2) in esophageal squamous cell carcinoma (ESCC) and ex- plore its role in ESCC carcinogenesis.METHODS: Se...AIM: To investigate the expression and methylation status of the secreted frizzled-related protein 2 (SFRP2) in esophageal squamous cell carcinoma (ESCC) and ex- plore its role in ESCC carcinogenesis.METHODS: Seven ESCC cell lines (KYSE 30, KYSE150, KYSE410, KYSE510, EC109, EC9706 and TE-1) and one immortalized human esophageal epithelial cell line (Het- 1A), 20 ESCC tissue samples and 20 paired adjacent non-tumor esophageal epithelial tissues were analyzed in this study. Reverse-transcription polymerase chain reaction (RT-PCR) was employed to investigate the expression of SFRP2 in cell lines, primary ESCC tumor tissue, and paired adjacent normal tissue. Methylation status was evaluated by methylation-specific PCR and bisulfite sequencing. The correlation between expres- sion and promoter methylation of the SFRP2 gene was confirmed with treatment of 5-aza-2'-deoxycytidine. To assess the potential role of SFRP2 in ESCC, we es-tablished stable SFRP2-transfected cells and examined them with regard to cell proliferation, colony formation, apoptosis and cell cycle in vivo and in vitro.RESULTS: SFRP2 mRNA was expressed in the im- mortalized normal esophageal epithelial cell line but not in seven ESCC cell lines. By methylation-specific PCR, complete methylation was detected in three cell lines with silenced SFRP2 expression, and extensive methylation was observed in the other four ESCC cell lines. 5-aza-2'-deoxycytidine could restore the expres- sion of SFRP2 mRNA in the three ESCC cell lines lack- ing SFRP2 expression. SFRP2 mRNA expression was obviously lower in primary ESCC tissue than in adjacent normal tissue (0.939 ± 0.398 vs 1.51 ± 0.399, P 〈 0.01). SFRP2 methylation was higher in tumor tissue than in paired normal tissue (95% vs 65%, P 〈 0.05). The DNA methylation status of the SFRP2 correlated inversely with the SFRP2 expression. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2 transfectants and control counterparts by in- troducing pcDNA3.1/v5 hisA -SFRP2 or pcDNA3.1/v5 hisA -empty vector into KYSE30 cells lacking SFRP2 expression. After transfection, the forced-expression of SFRP2 was confirmed by the RT-PCR. In comparison with the control groups, stably-expressed SFRP2 in KYSE 30 cells significantly reduced colony formation in vitro (47.17% 4± 15.61% vs 17% :1: 3.6%, P = 0.031) and tumor growth in nude mice (917.86:1:249.35 mm3 vs 337.23 ± 124.43 mm3, P 〈 0.05). Using flow cytom- etry analysis, we found a significantly higher number of early apoptotic cells in SFRP2-transfected cells than in the control cells (P = 0.025). The mean cell number in the S and G2-M phases of the cell cycle was also significantly lower in SFRP2-transfected KYSE30 cells compared with mock transfected counterparts. CONCLUSION: Silencing of SFRP2 expression through promoter hypermethylation may be a factor in ESCC carcinogenesis through loss of its tumor-suppressive activity.展开更多
Objective:The aim of this study was to investigate the af ecting of Rg3 to secreted VEGF of human laryngeal carcinoma Hep-2 cells and its mechanism of inhibition to tumor angiogenesis. Methods:Cultured human larynge...Objective:The aim of this study was to investigate the af ecting of Rg3 to secreted VEGF of human laryngeal carcinoma Hep-2 cells and its mechanism of inhibition to tumor angiogenesis. Methods:Cultured human laryngeal cancer cellline Hep-2 and human vascular endothelial cells in vitro, cells got into the period of exponential phase of growth, was diviced into 3 groups:group I (control group), group II (DDP group), group III (Rg3 group). Added to the Hep-2 cells Rg3 and DDP, made Rg3 final concentration was 300μg/mL, and DDP was 3μg/mL. 48 h later, specimens from sample to be done immunocytochemistry, and the protein of VEGF in Hep-2 cells to be detected. Col ecting Hep-2 cells supernatant, some was used to measure the protein level of VEGF in Hep-2 cells supernatant by ELISA. Some was used to culture HVEC. 24 h later, cellgrowth inhibition rate of human vascular endothelial was determined by MTT. Results:The protein level of VEGF was evi-dently higher in group I compared to group II and group III, it was not only in Hep-2 cells, but also in supernatant of Hep-2 cells. There was no significantly dif erent between group II and group III. MTT results showed that, the human vascular endothelial cellgrowth inhibition rate of group I was significantly lower than that of group II and group III (P〈0.05). At the same time the HVEC growth inhibition rate of group II was significantly lower than that of group III (P〈0.05). Conclusion:The inhibition to tumor angiogenesis of Rg3 is stronger than traditional chemotherapy drug cisplatin. It worke by reducing the biological ef ects of secreted VEGF, But the ef ecting worke by reducing the activity of secreted VEGF itself or af ecting endothelial function of VEGF receptor or some other ways to be further studied.展开更多
Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Inflammatory cells partici- pate in angiogenesis by secreting different molecules that affect endothelial celt ...Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Inflammatory cells partici- pate in angiogenesis by secreting different molecules that affect endothelial celt functions. We had previously shown that induced tissue factor (TF) expression in activated rnicrovascular endothelial celts (rn EC) is able to induce angiogenesis via autocrine regulation. However, the signals that induce TF expression in mEC are not fully known. Here, we demonstrate that rnonocyte paracrine cross-talk with mECs triggers rnEC-TF expression. We have identified that rnonocyte-secreted Wnt5a induces TF expression in rnEC and function-ally induces celt rnonolayer repair and angiotube formation in vitro as well as rnicrovesset formation in vivo. Monocyte-secreted Wnt5a activates FZD5 in mECs, which signals to induce the release of intraceUular Ca2+ and increase NFKB transcription activity and TF gene expression. In sum, WntSa secreted by monocytes signals through the noncanonical Wnt-FZD5 pathway in mECs to induce TF expression that induces angiogenesis by autocrine regulation.展开更多
In trauma, infection and hemorrhagic shock derived stress, primary and secondary injury may result in severe derangement in the internal environment. The abnormal changes of immune-mediated inflammation interfere its ...In trauma, infection and hemorrhagic shock derived stress, primary and secondary injury may result in severe derangement in the internal environment. The abnormal changes of immune-mediated inflammation interfere its pathogenesis and development directly. In recent years, various aspects of neuroendocrine responses, especially the regulatory effects of hypothalamic-pituitary-adrenal and sympathetico-adrenomedullary axes in inflammatory diseases have been the focus of research. Most importantly,corticotropin-releasing hormone (CRH) acts as a key player in the regulation of interactions between neuroendocrine and immunity both directly and indirectly. The paper summarized the recent development of CRH in the immune-mediated inflammation.展开更多
文摘Potassium (K+) ions are critical for the activation and catalytic cycle of the gastric H+,K+-ATPase, resulting in the secretion of hydrochloric acid into the parietal cell canaliculus. As both symptom, severity and esophageal mucosal damage in gastro-esophageal reflux disease (GERD) are related to the degree of acid exposure, K+ is a logical target for approaches to inhibit acid production.The probable K+ binding site on the gastric H+,K+-ATPase has recently been described and studies are elucidating how K+ activates the enzyme. K+ channels in the apical membrane of the parietal cell are implicated in the recycling of K+ and, to date, three potential K+ channels (KCNQ1, Kir2.1 and Kir4.1) have been identified. The channels represent theoretical sites for agents to control acid secretion but it will be difficult to develop selective blockers. An alternative strategy is to prevent K+ from activating gastric H+,K+-ATPase; the potassiumcompetitive acid blocker (P-CAB) class inhibits acidsecretion by binding at or near the K+ binding site.Ongoing research is further defining the role of K+ in the functioning of the gastric H+,K+-ATPase, as well as determining the clinical utility of agents directed toward this important cation.
基金Supported by Centre for Biomedical Genetics and Dutch Cancer Society RUL2005-3371(Hawinkels LJAC)
文摘AIM:To investigate the expression and potential prognostic role of vascular endothelial growth factor(VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors(GEP-NETs) . METHODS:Microvessel density(MVD) in GEP-NETs was evaluated using endoglin and CD31 immunohistochemistry.In addition,tissue levels of endoglin and VEGF were determined in homogenates by ELISA. RESULTS:Endoglin was highly expressed on tumor endothelial cells.CD31 MVD in GEP-NETs was significantly higher compared to endoglin MVD(P<0.01) .Two-tofour-fold higher tissue levels of endoglin and VEGF were seen in tumors compared to associated normal tissue. This increased endoglin tissue expression in tumors was significantly related to tumor size(P<0.01) ,presence of metastases(P=0.04) ,and a more advanced tumor stage(P=0.02) ,whereas expression of VEGF was not. CONCLUSION:We suggest that endoglin is a potential marker to indicate and predict metastases,which might be useful in the post-resection therapeutic approach of patients with GEP-NETs.
文摘Vanishing bile duct syndromes (VBDS) are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA), a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes. Several potential mechanisms of action of UDCA have been proposed including stimulation of hepatobiliary secretion, inhibition of apoptosis and protection of cholangiocytes against toxic effects of hydrophobic bile acids.
文摘The levels of somatostatin(SS)in CSF and blood and pancreatic polypeptide(PP)inplasma were measured by radioimmunoassay in 64 patients with acute ischemiccerebrovascular diseases(ICVD),randomly divided into two groups:group 1(n=31,bothelectro-acupuncture and routine treatments given)and group 2(n=33,routine treatment)and 26 non-ICVD patients were used as controls.The points of electro-acupuncture wereQuchi(LI 12),Waiguan(SJ 5)and Huantiao(GB 30)and Zusanli(St 36).After a courseof treatment,the SS levels in plasma and CSF were significantly increased in the patientsof group 1 with good result and their plasma PP level had no significant change.In thepatients with poor result,however,the PP level was significantly decreased.The resultssuggested that electro-acupuncture might play an active role in alleviating the SSmetabolic disturbance in CNS of ICVD patients.
基金Supported by a Wellcome Trust IRDA Grant to P.H. (No. 022618)Hungarian Scientific Research Funds to P.H. and J.L. (No. D42188,T43066)a Wellcome Trust Travelling Fellowship to Z.R. (No. 069470)a Bolyai Postdoctoral Fellowship to P.H. (No. 00276/04)a National Fund for Scientific Research (OTKA) to Z.B. (No. T049171)
文摘AIM: To examine the effect of acute infection caused by herpesvirus (pseudorabies virus, PRV) on pancreatic ductal secretion. METHODS: The virulent Ba-DupGreen (BDG) and non- virulent Ka-RREp01acgfp (KEG) genetically modified strains of PRV were used in this study and both of them contain the gene for green fluorescent protein (GFP). Small intra/ interlobular ducts were infected with BDG virus (10^7 PFU/mL for 6 h) or with KEG virus (10^10 PFU/mL for 6 h), while non-infected ducts were incubated only with the culture media. The ducts were then cultured for a further 18 h. The rate of HCO3 secretion [base efflux -λ(B)] was determined from the buffering capacity of the cells and the initial rate of intracellular acidification (1) after sudden blockage of basolateral base loaders with dihydro-4,4,- diisothiocyanatostilbene-2,2,-disulfonic acid (500 μmol/L) and amiloride (200 μmol/L), and (2) after alkali loading the ducts by exposure to NH4Cl. All the experiments were performed in HCO3-buffered Ringer solution at 37 ℃ (n = 5 ducts for each experimental condition). Viral structural proteins were visualized by immunohistochemistry. Virallyencoded GFP and immunofluorescence signals were recorded by a confocal laser scanning microscope.RESULTS: The BDG virus infected the majority of accessible cells of the duct as judged by the appearance of GFP and viral anUgens in the ductal cells. KEG virus caused a similarly high efficiency of infection. After blockage of basolateral base loaders, BDG infection significantly elevated -λB-) 24 h after the infection, compared to the non-infected group. However, KEG infection did not modify -λB-). After alkali loading the ducts, -λB-) was significantly elevated in the BDG group compared to the control group 24 h after the infection. As we found with the inhibitor stop method, no change was observed in the group KEG compared to the non-infected group. CONCLUSION: Incubation with the BDG or KEG strains of PRV results in an effective infection of ductal epithelial cells. The BDG strain of PRV, which is able to initiate a lytic viral cycle, stimulates HCO3 secretion in guinea pig pancreatic duct by about fourto fivefold, 24 h after the infection. However, the KEG strain of PRV, which can infect, but fails to replicate, has no effect on HCO3 secretion. We suggest that this response of pancreatic ducts to virulent PRV infection may represent a defense mechanism against invasive pathogens to avoid pancreatic injury.
文摘We report 2 cases of pancreatic endocrine tumors that caused obstruction of the main pancreatic duct(MPD).A 49-year-old asymptomatic man was referred to our institution because dilation of the MPD was revealed by abdominal ultrasonography(US).No tumor was detected by endoscopic ultrasonography,computed tomography(CT),and magnetic resonance imaging(MRI).The diameter of the MPD was > 20 mm at the body,and no dilation was noted at the head.Although malignancy was not confirmed through cytology or imaging,pancreatic cancer was strongly suspected.Pancreaticoduo-denectomy was performed.Pathological and immunohistochemical examination revealed a 5 mm × 3 mm serotonin-positive endocrine tumor.Fibrosis was present around the MPD and seemed to cause stricture.A 32-year-old asymptomatic man had elevated serum amylase,and US demonstrated dilation of the MPD.No tumor was detected by CT and MRI.Pancreatic cancer was suspected due to stricture and dilation of the MPD.Pancreatectomy of middle part of pancreas was performed.Pathological and immunohistochemical examination revealed a serotonin-positive endocrine tumor sized 5 mm × 4 mm.We report 2 cases of serotonin-positive pancreatic endocrine tumors that caused stricture of the MPD in spite of the small size of the tumor.
文摘AIM: To investigate the effects of taurolithocholate (TLC)on the canalicular motility in isolated rat hepatocyte cou-plets (IRHC).METHODS: TLC was added to IRHC at concentrationsof 10 and 50 μmol/L, respectively. In each group, fi vetime-lapse movies containing 3 representative bile cana-liculi were taken under phase-contrast microscopy for12 h. The number of bile canalicular contractions andthe intervals between consecutive canalicular contrac-tions were calculated. Furthermore, the effects of TLC onIRHC were examined by transmission electron micros-copy.RESULTS: The bile canalicular contractions were spon-taneous and forceful in the controls. Active vesicularmovement was observed in the pericanalicular region.Immediately after the addition of TLC, the bile canaliculiwere deformed, and canalicular bile was incorporatedinto the vacuoles. The canaliculi were gradually dilated,and canalicular contractions were markedly inhibited byTLC. The vesicular movements became extremely slowin the pericanalicular region. The number of canalicularcontractions significantly decreased in the TLC-treatedgroups, as compared with that in the controls. The timeintervals were prolonged, as the TLC dosage increased,indicating that bile secretion into the canaliculi wasimpaired with TLC. Transmission electron microscopyrevealed the lamellar transformation of the canalicularmembranes in IRHC treated with TLC.CONCLUSION: TLC impairs both the bile canalicularcontractions and the canalicular bile secretion, possiblyby acting directly on the canalicular membranes in TLC-induced cholestasis.
文摘Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT) and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.
文摘Introduction Neuroendocrine tumor covers a wide range of neoplasms that originate in the neuroendocrine cells which spread throughout the body. Carcinoid tumor,
基金supported by grants from the key program of the National Basic Research Program of China (973 program) (Grant No. 2012CB9333004)the National Natural Science Foundation of China (Grant No. 81401888)
文摘Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors(VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells(DCs), macrophages, and lymphocytes further express certain types of VEGF receptors.VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness.This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.
文摘Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Antioxidants have been used in various studies to improve islet transplantation procedures. The present study reviews the role of oxidative stress and the benefits of antioxidants in islet transplantation procedures. The bibliographical databases Pubmed and Scopus were searched up to November 2008. All relevant human and animal in-vivo and in-vitro studies, which investigated antioxidants on islets, were included. Almost all the tested antioxidants used in the in-vitro studies enhanced islet viability and insulin secretion. Better control of blood glucose after transplantation was the major outcome of antioxidant therapy in all in-vivo studies. The data also indicated that antioxidants improved islet transplantation procedures. Although there is still insuffi cient evidence to draw definitive conclusions about the efficacy of individual supplements, the benefi ts of antioxidants in islet isolation procedures cannot be ignored.
基金supported by the Key State Basic Research and Development Program(G1999012002)the National Natural Science Foundation(30271016)+1 种基金a research grant of the Key Laboratory of Mariculture,Ministry of Education,Ocean University of China(LMMEC)(200210)the Changjiang Scholars Program of China
文摘Structure and function of the digestive system of a bivalve mollusc, Solen grandis, were studied using light microscopy and histochemical methods. The wall of digestive tube consists of four layers: the mucosal epithelium, connective tissue, muscular and fibrosa or serosa (only in the portion of rectum) from the inner to the outer. The ciliated columnar epithelial cells, dispersed by cup-shaped mucous cells, rest on a thin base membrane. There are abundant blood spaces in connective tissue layer. The digestive diverticula are composed of multi-branched duct and digestive tubules. The digestive tubules are lined with digestive and basophilic secretory cells, and surrounded by a layer of smooth muscle fibers and connective tissues. Activities of acid and alkaline phosphatases, esterase and lipase are detected in the digestive cells, and the epithelia of stomach and intestine, suggesting that these cells are capable of intracellular digesting of food materials and absorbing.Besides, acid phosphatase and esterase activities are present in the posterior portion of esophagus. Phagocytes are abundant in blood spaces and the lumens of stomach and intestine, containing brown granules derived from the engulfed food materials. The present work indicates that phagocytes play important roles in ingestion and digestion of food materials, which is supported as well by the activities of acid phosphatase, esterase and lipase detected in blood spaces.
基金Supported by National Natural Science Foundation of China,No. 81050016Research Fund for the Doctoral Program of Higher Education of China,No. 200800250003
文摘AIM: To investigate the expression and methylation status of the secreted frizzled-related protein 2 (SFRP2) in esophageal squamous cell carcinoma (ESCC) and ex- plore its role in ESCC carcinogenesis.METHODS: Seven ESCC cell lines (KYSE 30, KYSE150, KYSE410, KYSE510, EC109, EC9706 and TE-1) and one immortalized human esophageal epithelial cell line (Het- 1A), 20 ESCC tissue samples and 20 paired adjacent non-tumor esophageal epithelial tissues were analyzed in this study. Reverse-transcription polymerase chain reaction (RT-PCR) was employed to investigate the expression of SFRP2 in cell lines, primary ESCC tumor tissue, and paired adjacent normal tissue. Methylation status was evaluated by methylation-specific PCR and bisulfite sequencing. The correlation between expres- sion and promoter methylation of the SFRP2 gene was confirmed with treatment of 5-aza-2'-deoxycytidine. To assess the potential role of SFRP2 in ESCC, we es-tablished stable SFRP2-transfected cells and examined them with regard to cell proliferation, colony formation, apoptosis and cell cycle in vivo and in vitro.RESULTS: SFRP2 mRNA was expressed in the im- mortalized normal esophageal epithelial cell line but not in seven ESCC cell lines. By methylation-specific PCR, complete methylation was detected in three cell lines with silenced SFRP2 expression, and extensive methylation was observed in the other four ESCC cell lines. 5-aza-2'-deoxycytidine could restore the expres- sion of SFRP2 mRNA in the three ESCC cell lines lack- ing SFRP2 expression. SFRP2 mRNA expression was obviously lower in primary ESCC tissue than in adjacent normal tissue (0.939 ± 0.398 vs 1.51 ± 0.399, P 〈 0.01). SFRP2 methylation was higher in tumor tissue than in paired normal tissue (95% vs 65%, P 〈 0.05). The DNA methylation status of the SFRP2 correlated inversely with the SFRP2 expression. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2 transfectants and control counterparts by in- troducing pcDNA3.1/v5 hisA -SFRP2 or pcDNA3.1/v5 hisA -empty vector into KYSE30 cells lacking SFRP2 expression. After transfection, the forced-expression of SFRP2 was confirmed by the RT-PCR. In comparison with the control groups, stably-expressed SFRP2 in KYSE 30 cells significantly reduced colony formation in vitro (47.17% 4± 15.61% vs 17% :1: 3.6%, P = 0.031) and tumor growth in nude mice (917.86:1:249.35 mm3 vs 337.23 ± 124.43 mm3, P 〈 0.05). Using flow cytom- etry analysis, we found a significantly higher number of early apoptotic cells in SFRP2-transfected cells than in the control cells (P = 0.025). The mean cell number in the S and G2-M phases of the cell cycle was also significantly lower in SFRP2-transfected KYSE30 cells compared with mock transfected counterparts. CONCLUSION: Silencing of SFRP2 expression through promoter hypermethylation may be a factor in ESCC carcinogenesis through loss of its tumor-suppressive activity.
文摘Objective:The aim of this study was to investigate the af ecting of Rg3 to secreted VEGF of human laryngeal carcinoma Hep-2 cells and its mechanism of inhibition to tumor angiogenesis. Methods:Cultured human laryngeal cancer cellline Hep-2 and human vascular endothelial cells in vitro, cells got into the period of exponential phase of growth, was diviced into 3 groups:group I (control group), group II (DDP group), group III (Rg3 group). Added to the Hep-2 cells Rg3 and DDP, made Rg3 final concentration was 300μg/mL, and DDP was 3μg/mL. 48 h later, specimens from sample to be done immunocytochemistry, and the protein of VEGF in Hep-2 cells to be detected. Col ecting Hep-2 cells supernatant, some was used to measure the protein level of VEGF in Hep-2 cells supernatant by ELISA. Some was used to culture HVEC. 24 h later, cellgrowth inhibition rate of human vascular endothelial was determined by MTT. Results:The protein level of VEGF was evi-dently higher in group I compared to group II and group III, it was not only in Hep-2 cells, but also in supernatant of Hep-2 cells. There was no significantly dif erent between group II and group III. MTT results showed that, the human vascular endothelial cellgrowth inhibition rate of group I was significantly lower than that of group II and group III (P〈0.05). At the same time the HVEC growth inhibition rate of group II was significantly lower than that of group III (P〈0.05). Conclusion:The inhibition to tumor angiogenesis of Rg3 is stronger than traditional chemotherapy drug cisplatin. It worke by reducing the biological ef ects of secreted VEGF, But the ef ecting worke by reducing the activity of secreted VEGF itself or af ecting endothelial function of VEGF receptor or some other ways to be further studied.
文摘Angiogenesis during reactive and pathologic processes is characteristically associated with inflammation. Inflammatory cells partici- pate in angiogenesis by secreting different molecules that affect endothelial celt functions. We had previously shown that induced tissue factor (TF) expression in activated rnicrovascular endothelial celts (rn EC) is able to induce angiogenesis via autocrine regulation. However, the signals that induce TF expression in mEC are not fully known. Here, we demonstrate that rnonocyte paracrine cross-talk with mECs triggers rnEC-TF expression. We have identified that rnonocyte-secreted Wnt5a induces TF expression in rnEC and function-ally induces celt rnonolayer repair and angiotube formation in vitro as well as rnicrovesset formation in vivo. Monocyte-secreted Wnt5a activates FZD5 in mECs, which signals to induce the release of intraceUular Ca2+ and increase NFKB transcription activity and TF gene expression. In sum, WntSa secreted by monocytes signals through the noncanonical Wnt-FZD5 pathway in mECs to induce TF expression that induces angiogenesis by autocrine regulation.
基金This work was supported by the Special Funds for Major State Basic Research Projects (2005CB522600), the Eleventh Five-Year Science and Technology Project of PLA (06G080), and Natural Science Foundation Project of CQCSTC (2009BB5316)
文摘In trauma, infection and hemorrhagic shock derived stress, primary and secondary injury may result in severe derangement in the internal environment. The abnormal changes of immune-mediated inflammation interfere its pathogenesis and development directly. In recent years, various aspects of neuroendocrine responses, especially the regulatory effects of hypothalamic-pituitary-adrenal and sympathetico-adrenomedullary axes in inflammatory diseases have been the focus of research. Most importantly,corticotropin-releasing hormone (CRH) acts as a key player in the regulation of interactions between neuroendocrine and immunity both directly and indirectly. The paper summarized the recent development of CRH in the immune-mediated inflammation.