To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4(LTB4) induced by cyclic stretching of human patellar tendon fibroblasts.Methods We used a novel...To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4(LTB4) induced by cyclic stretching of human patellar tendon fibroblasts.Methods We used a novel in vitro model system to mimic in vivo conditions,where human patellar tendon fibroblasts (HPTFs) were uniaxially stretched with different magnitudes of stretching (4%,8% and 12%).Non-stretched fibroblasts were used as control.The productions of PGE2 and LTB4 as well as the expression of cycloxygenase (COX) and 5-lipoxygenase (5-LO) were then measured every four hours of cyclic stretching.In addition,we treated the cells with inhibitors of COX or 5-LO.Results It was found that cyclic stretching of fibroblasts at 8% and 12% of stretching increased PGE2 and LTB4 levels.Blocking the COX enzyme with indomethacin (25 mol/L) decreased PGE2 levels but increased LTB4 production and vice versa.Whereas decreasing LTB4 production with MK-886 (10 μmol/L) could increase PGE2 levels compared to cells tretched without inhibitors.Conclusion Cyclic stretching of HPTFs produces high levels of PGE2 and LTB4,where a balance exists:blocking PGE2 production increases the production of LTB4,and vice versa.Therefore,this study raises the possibility that the routine use of COX inhibitors in clinical treatment of tendinopathy may exacerbate the condition by causing neutrophil-mediated inflammatory and degenerative changes in the tendon due to increased levels of LTB4,which is a potent chemoattractant for neutrophils.17 refs,3 figs.展开更多
Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores ...Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.展开更多
BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal fu...BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal function after LT have not yet been well described.AIM To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant.METHODS This retrospective study included all patients who underwent liver or liverkidney transplant at our institution from January,2011 to December,2021.Patients were classified based on whether they received PGE1.PGE1 was administered post-LT to those with transaminases>1000 U/L in the immediate postoperative period.Demographics,post-LT treatments and/or complications,renal function,and survival were analyzed.Multivariable logistic regression analysis was performed,and a two-tailed P value<0.05 was considered statistically significant.RESULTS A total of 145 patients underwent LT,with 44(30%)receiving PGE1.Baseline patient characteristics were comparable,except the PGE1 group had significantly higher aspartate aminotransferase(AST)(1961.9 U/L±1862.3 U/L vs 878 U/L±741.4 U/L,P=0.000),alanine aminotransferase(1070.6 U/L±895 U/L vs 547.7 U/L±410 U/L,P=0.000),international normalized ratio on post-LT day 1(2±0.74 vs 1.8±0.4,P=0.03),a longer intensive care unit stay(8.1 days±11.8 days vs 3.8 days±4.6 days,P=0.003),more vasopressor use(55.53 hours±111 hours vs 16.33 hours±26.3 hours,P=0.002),and higher immediate postoperative complications(18.6%vs 4.9%,P=0.04).The PGE1 group also had a significantly higher 90-day readmission rate(29.6%vs 13.1%,P=0.02)and lower 1-year liver graft survival(87.5%vs 98.9%,P=0.005).However,30-day readmission(31.6%vs 27.4%,P=0.64),LT complications(hepatic artery thrombosis,biliary complications,rejection of liver graft,cardiomyopathy),1-year patient survival(96.9%vs 97.8%,P=0.77),overall liver graft survival,and overall patient survival were similar between the two groups(95.4%vs 93.9%,P=0.74 and 88.4%vs 86.9%,P=0.81 respectively).Although the PGE1 group had a significantly lower glomerular filtration rate(eGFR)on post-LT day 7(46.3 mL/minute±26.7 mL/minute vs 62.5 mL/minute±34 mL/minute,P=0.009),the eventual need for renal replacement therapy(13.6%vs 5.9%,P=0.09),the number of dialysis sessions(0.91 vs 0.27,P=0.13),and eGFR at 1-month(37.2 mL/minute±35.9 mL/minute vs 42 mL/minute±36.9 mL/minute,P=0.49),6-months(54.8 mL/minute±21.6 mL/minute vs 62 mL/minute±21.4 mL/minute,P=0.09),and 12-months(63.7 mL/minute±20.7 mL/minute vs 62.8 mL/minute±20.3 mL/minute,P=0.85)post-LT were similar to those in the non-PGE1 group.CONCLUSION In patients who received PGE1 for ischemia-reperfusion injury,despite immediate acute renal injury post-LT,the renal function at 1-month,6-months,and 12-months post-LT was similar compared to those without ischemiareperfusion injury.Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.展开更多
Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandi...Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandin E1 on platelet aggregation function [ PAG (5,) PAG( m ) ], serum total protein (TP) , albumin (Al),blood urea nitrogen(BUN) ,serum creatinine(Scr) ,cholesterol(CHO), triglyceride(TG), protein in 24-hour urine (Pr/24h) and platelet account (PLT). Results: TP, Al, CHO, TG, BUN, Scr, Pr/24h, PAG(5) and PAG(m) in PNS group before treatment were significantly different from those in control group(P＜0.05, P＜0.01) while no significant difference was found for PLT. When treated with PGE1 , TP,Al,CHO, TG, Pr/24h, ADP- induced PAG(5) ,and Adr- induced PAG(5) and PAG(m) were significantly different from those before treatment (P＜0.05). Adr- induced PAG(5) and PAG(m) were significantly different. Adr- induced PAG(5) was xsitively correlated with BUN and Scr in PNS(P＜0.01). Similar correlation was found between ADP-induced PAG(5) and Al ,BUN,Scr,Pr/24h(P＜0.05), AD- induced PAG(m) and TP,CHO(P＜0.05). Conclusions: PGE1 may be an effective drug for the treatment for hypercoagulation in patients with PNS.展开更多
Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neura...Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neural pathways. In this review, we first briefly summarize current views on the mechanism of sensing microbial infection by the nervous system, and the roles of prostaglandin E2 （PGE2） and its receptors in fever; then we focus on the neural circuits underlying fever generation, particularly their relationship with the distribution of PGE2 receptors within the CNS. At the end, an overall neurochemical model of fever generation is presented, pointing to the direction for future studies.展开更多
AIM:To study the effect of moxibustion on Zusanli or Liangmeng point on gastric mucosa injury in stress-induced ulcer rats and its correlation with the expression of heat shock protein 70 (HSP70). METHODS:Sixty health...AIM:To study the effect of moxibustion on Zusanli or Liangmeng point on gastric mucosa injury in stress-induced ulcer rats and its correlation with the expression of heat shock protein 70 (HSP70). METHODS:Sixty healthy SD rats (30 males,30 females) were divided into control group,injury model group,Zushanli point group,Liangmeng point group. Stress gastric ulcer model was induced by binding cold stress method. Gastric mucosa ulcer injury (UI) index was calculated by Guth method. Gastric mucosa blood flow (GMBF) was recorded with a biological signal analyzer. Protein content and gene expression in gastric mucosal HSP70 were detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). Thiobarbital method was used to determine malondialdehyde (MDA) content. Gastric mucosal endothelin (ET) and prostaglandin E2 (PGE2) were analyzed by radioimmunoassay. RESULTS:High gastric mucosal UI index,high HSP70 expression,low GMBF and PGF2,elevated MDA and ET were observed in gastric mucosa of rats subjected to cold stress. Moxibustion on Zusanli or Liangmeng point decreased rat gastric mucosal UI index,MDA and ET. Conversely,the expression of HSP70,GMBF,and PGE2 was elevated in gastric mucosa after pretreatment with moxibustion on Zusanli or Liangmeng point. The observed parameters were significantly different between Zusanli and Liangmeng points. CONCLUSION:Pretreatment with moxibustion on Zusanli or Liangmeng point protects gastric mucosa against stress injury. This protection is associated with the higher expression of HSP70 mRNA and protein,leading to release of PGE2 and inhibition of MDA and ET,impairment of gastric mucosal index.展开更多
AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated fro...AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.展开更多
AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human co...AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control. RESULTS Our results showed that 20 mu mol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3 beta, and beta-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of beta-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice. CONCLUSION TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.展开更多
AIM: To examine the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in rat esophageal lesions induced by reflux of duodenal contents.
Objective: To evaluate the serum Prostaglandin E2(PGE2) level in Acute-on-chronic liver failure(ACLF) and determine its predicative value for infection.Methods: From April 2014 to April 2015, ninety-one patients with ...Objective: To evaluate the serum Prostaglandin E2(PGE2) level in Acute-on-chronic liver failure(ACLF) and determine its predicative value for infection.Methods: From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating characteristic(ROC) curves were used to determine optimal cut-off values to predict infection.Results: Significantly higher PGE2 levels were found in patients with ACLF in comparison with healthy controls and patients with stable CHB(P < 0.000 1). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication(P < 0.000 1). ROC analysis showed that serum PGE2(area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/m L.Conclusions: Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.展开更多
Gastric cancer accounts for the majority cancer-related deaths worldwide.Although various methods have considerably improved the screening,diagnosis,and treatment of gastric cancer,its incidence is still high in Asia,...Gastric cancer accounts for the majority cancer-related deaths worldwide.Although various methods have considerably improved the screening,diagnosis,and treatment of gastric cancer,its incidence is still high in Asia,and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%.Therefore,more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer.Cyclooxygenase-2(COX-2)is considered to be the key inducible enzyme in prostaglandins(PGs)synthesis,which is involved in multiple pathways in the inflammatory response.For example,inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway.In these processes,the production of an inflammatory microenvironment promotes the occurrence of gastric cancer.Epidemiological studies have also indicated that non-steroidal antiinflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2.However,clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects,especially in the cardiovascular system.Given these side effects and low treatment efficacy,new therapeutic approaches and early screening strategies are urgently needed.Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis.However,the genetic variation analysis in these studies is incomplete and isolated,pointing out only a few single nucleotide polymorphisms(SNPs)and the risk of gastric cancer,and no comprehensive study covering the whole gene region has been carried out.In addition,copy number variation(CNV)is not mentioned.In this review,we summarize the SNPs in the whole COX-2 gene sequence,including exons,introns,and both the 5’and 3’untranslated regions.Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population.This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies,summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer,and discusses the future prospect of therapeutic intervention,which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.展开更多
AIM: To examine the effect of prostaglandin E2 (PGE2) on the expression of vascular endothelial growth factor (VEGF) mRNA in the human hepatocellular carcinoma (HCC) HepG2 cells and the possible involvement of c-fos p...AIM: To examine the effect of prostaglandin E2 (PGE2) on the expression of vascular endothelial growth factor (VEGF) mRNA in the human hepatocellular carcinoma (HCC) HepG2 cells and the possible involvement of c-fos protein in this process.METHODS: Human HCC HepG2 cells were divided into three groups treated respectively with PGE2, a combination of PGE2 and c-fos antisense oligodeoxynucleotide (ASO),and PGE2 plus c-fos sense oligodeoxynudeotide (SO). The expression of VEGF mRNA in HepG2 cells after different treatments was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The relative expression level of VEGF mRNA in HepG2 cells in each group was measured.RESULTS: Administration of PGE2 resulted in an increased expression of c-fosand VEGF mRNA in HepG2 cells. The relative expression level of c-fos mRNA reached the peak at 3 h (68.4±4.7%) after PGE2 treatment, which was significantly higher than that at 0 h (20.6±1.7%, P＜0.01).Whereas, the highest expression level of VEGF mRNA was observed at 6 h (100.5±6.1%) after PGE2 treatment, which was significantly higher than that at 0 h (33.2±2.4%,P＜0.01). C-fos ASO significantly reduced PGE2-induced VEGF mRNA expression in HepG2 cells.CONCLUSION: PGE2 increases the expression and secretion of VEGF in HCC cells by activating the transcription factor c-fos, promotes the angiogenesis of HCC and plays an important role in the pathogenesis of liver cancer.展开更多
Objective To investigate the effects of prostaglandin E1 (PGE1) on the progression of aristolochic acid nephropathy (AAN). Methods Twenty-four patients diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL an...Objective To investigate the effects of prostaglandin E1 (PGE1) on the progression of aristolochic acid nephropathy (AAN). Methods Twenty-four patients diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL and 4 mg/dL during September 2001 to August 2003 were randomly divided into 2 groups. All patients had ingested long dan xie gan wan con-taining aristolochic acid (0.219 mg/g) for at least 3 months. Twelve patients were injected with Alprostadil (10 μg/d for 10 days in one month, summing up to 6 months). Except for PGE1, the other therapy was same in both groups. Renal function was assessed using reciprocal serum creatinine levels (1/Scr). Results The level of Scr and serum hemoglobin (Hgb) was similar in both groups prior to therapy. During follow-up, 1/Scr levels in PGE1 group were significantly higher than control group (P < 0.01), and Hgb levels in PGE1 group were sig-nificantly increased compared with control (P < 0.05).Conclusion PGE1 can slow the progression of renal failure and increase Hgb level of AAN patient.展开更多
AIM to determine whether cyclooxygenase-2(COX-2) and prostaglandin E1 receptor(EP1) contribute to disease and whether they help predict prognosis.METHODS We retrospectively reviewed the records of 116 patients with he...AIM to determine whether cyclooxygenase-2(COX-2) and prostaglandin E1 receptor(EP1) contribute to disease and whether they help predict prognosis.METHODS We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma(HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffinembedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were determined.RESULTS Factors associated with poor overall survival(OS) were alpha-fetoprotein > 400 ng/m L, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues(Edmondson grade Ⅰ-Ⅱ) than in poorly differentiated tissues(Edmondson grade Ⅲ-Ⅳ)(P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue(P = 0.001).CONCLUSION COX-2 expression appears to be linked to early HCC events(initiation), while EP1 receptor expression may participate in tumor progression and predict survival.展开更多
AIM： To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanoltreated rat＇s stomach to naproxen （NAP）. METHODS： Male Sprague-Dawley rats were pretreated with 1 mL of 50% etha...AIM： To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanoltreated rat＇s stomach to naproxen （NAP）. METHODS： Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP （50 mg/kg） was administered. DA-9601 was admin- istered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index （mm2）, histologic change and to determine mucosal levels of malondialdehyde （MDA）, prostaglandin E2 （PGE2）, glutathione （GSH） and myeloperoxidase （MPO）. RESULTS： Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in NDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAR DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats （P〈0.05）, with reduction in mucosal MDA and MPO levels. CONCLUSION： These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved.展开更多
In order to evaluate the effects and mechanisms of celecoxib in inhibiting proliferation and inducing apoptosis on human pancreatic carcinoma cells, the anti-proliferative effect was measured by using methabenzthiazur...In order to evaluate the effects and mechanisms of celecoxib in inhibiting proliferation and inducing apoptosis on human pancreatic carcinoma cells, the anti-proliferative effect was measured by using methabenzthiazuron (MTT) assay. Cell cycle and apoptosis were analyzed by using flow cytometry (FCM), and the PGE 2 levels in the supernatant of cultured pancreatic carcinoma cells were quantitated by enzyme-linked immunoabsordent assay (ELISA). Our results showed that celecoxib suppressed the production of PGE 2 and inhibited the growth of JF-305 cells, and the anti-proliferative effect of celecoxib could be abolished by addition of PGE 2. FCM revealed that celecoxib could inhibit proliferation and induce apoptosis by G 1-S cell cycle arrest. It was concluded that cyclooxygenase-2 specific inhibitor celecoxib could inhibit proliferation and induced apoptosis of human pancreatic carcinoma cells via suppression of PGE 2 production in vitro.展开更多
AIM: To investigate the effect of lipopolysaccharide (LPS)on the diarrheogenic activity, gastrointestinal transit (GIT),and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE...AIM: To investigate the effect of lipopolysaccharide (LPS)on the diarrheogenic activity, gastrointestinal transit (GIT),and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastrointestinal functions of endotoxin-treated mice.METHODS: Diarrheogic activity, GIT, and intestinal fluid content as well as nitric oxide and PGE2 products were measured after intraperitoneal administration of LPS in mice.RESULTS: LPS dose-dependently accumulated abundant fluid into the small intestine, induced diarrhea, but decreased the GIT. Both nitric oxide and PGE2 were found to increase in LPS-treated mice. Western blot analysis indicated that LPS significantly induced the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in mice intestines. Pretreatment with NG-nitro-L-arginine-methyl ester (L-NAME, a non-selective NOS inhibitor) or indomethacin (an inhibitor of prostaglandin synthesis) significantly attenuated the effects of LPS on the diarrheogenic activity and intestine content, but reversed the GIT.CONCLUSION: The present study suggests that the pathogenesis of LPS treatment may mediate the stimulatory effect of LPS on nitric oxide and PGE2 production and NO/prostaglandin pathway may play an important role on gastrointestinal function.展开更多
Streptococcus mitis （S. mitis） is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction wit...Streptococcus mitis （S. mitis） is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction with the host. We used examination of its transcriptional regulation in oral keratinocytes to elucidate some of its potential roles in the oral cavity. Transcription factor analysis of oral keratinocytes predicted S. mitis.mediated activation of aryl hydrocarbon receptor （AhR）, Activation and functionality of AhR was confirmed through nuclear translocation determined by immunofluorescence microscopy and real-time polymerase chain reaction with reverse transcription analysis of CYPIA1, the hallmark gene for AhR activation. Addition of Streptococcus mutans or Streptococcus gordonfi did not induce CYPIA1 transcription in the keratinocyte cultures. Introduction of an AhR-specific inhibitor revealed that S. mitis-mediated transcription of CXCL2 and CXCL8 was regulated by AhR. Elevated levels of pmstaglandin E2 （enzyme-linked immunosorbent assay） in supernatants from S. mitis-treated oral epithelial cells were also attenuated by inhibition of AhR activity. The observed AhR-regulated activities point to a contribution of S. mitis in the regulation of inflammatory responses and thereby to wound healing in the oral cavity. The concept that the oral commensal microbiota can induce AhR activation is important, also in view of the role that AhR has in modulation of T-cell differentiation and as an anti-inflammatory factor in macrophaees.展开更多
AIM:To investigate whether microsomal prostaglandin E synthase-1 (mPGES-1) expression in hepatocellular carcinoma (HCC) and in non-cancerous liver affects HCC prognosis after hepatectomy. METHODS: The relationship bet...AIM:To investigate whether microsomal prostaglandin E synthase-1 (mPGES-1) expression in hepatocellular carcinoma (HCC) and in non-cancerous liver affects HCC prognosis after hepatectomy. METHODS: The relationship between patient clinical prof iles, tumor factors, surgical determinants, and mPGES-1 expression and the recurrence-free survival rate were examined in 64 patients who underwent curative hepatectomy between March 2003 and December 2006. RESULTS: The scores for mPGES-1 expression were higher in well differentiated and moderately differentiated HCC tissues than in poorly differentiated HCC tissues (well differentiated, 5.1 ± 2.7; moderately differentiated, 5.1 ± 1.7; poorly differentiated, 3.0 ± 1.8). In noncancerous liver tissues, the mPGES-1 levels were higher in injured liver tissues than in normal tissues. Cirrhotic livers had higher mPGES-1 levels than livers with chronic hepatitis (normal livers, 3.3 ± 0.7; chronic hepatitic livers, 5.4 ± 1.9; cirrhotic livers, 6.4 ± 1.6). A univariate analysis revealed that the recurrence-free survival rate was signif icantly lower in patients with vascular invasion,a higher mPGES-1 level in non-cancerous liver tissue,a larger tumor diameter (≥5 cm), and a lower serum albumin level (≤3.7 g/dL). The mPGES-1 expression in HCC tissues did not correlate well with postoperative recurrence. A multivariate analysis demonstrated that the presence of vascular invasion and higher mPGES-1 levels were statistically significant independent predictors for early postoperative recurrence of HCC.CONCLUSION: Increased mPGES-1 expression in noncancerous liver tissues is closely associated with the early recurrence of HCC after curative resection.展开更多
文摘To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4(LTB4) induced by cyclic stretching of human patellar tendon fibroblasts.Methods We used a novel in vitro model system to mimic in vivo conditions,where human patellar tendon fibroblasts (HPTFs) were uniaxially stretched with different magnitudes of stretching (4%,8% and 12%).Non-stretched fibroblasts were used as control.The productions of PGE2 and LTB4 as well as the expression of cycloxygenase (COX) and 5-lipoxygenase (5-LO) were then measured every four hours of cyclic stretching.In addition,we treated the cells with inhibitors of COX or 5-LO.Results It was found that cyclic stretching of fibroblasts at 8% and 12% of stretching increased PGE2 and LTB4 levels.Blocking the COX enzyme with indomethacin (25 mol/L) decreased PGE2 levels but increased LTB4 production and vice versa.Whereas decreasing LTB4 production with MK-886 (10 μmol/L) could increase PGE2 levels compared to cells tretched without inhibitors.Conclusion Cyclic stretching of HPTFs produces high levels of PGE2 and LTB4,where a balance exists:blocking PGE2 production increases the production of LTB4,and vice versa.Therefore,this study raises the possibility that the routine use of COX inhibitors in clinical treatment of tendinopathy may exacerbate the condition by causing neutrophil-mediated inflammatory and degenerative changes in the tendon due to increased levels of LTB4,which is a potent chemoattractant for neutrophils.17 refs,3 figs.
基金Supported by the National High-Level Hospital Clinical Research Fund,No.2022-PUMCH-A-020the Undergraduate Teaching Reform and Innovation Project,No.2022zlgc0108.
文摘Chronic enteropathy associated with the SLCO2A1 gene(CEAS)is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss.This review explores the potential mechanisms underlying the pathogenesis of CEAS,focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2(PGE2)levels.Studies have suggested that elevated PGE2 levels contribute to mucosal damage,inflammation,and disruption of the intestinal barrier.The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality,as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS.Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel,targeted therapies.
文摘BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal function after LT have not yet been well described.AIM To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant.METHODS This retrospective study included all patients who underwent liver or liverkidney transplant at our institution from January,2011 to December,2021.Patients were classified based on whether they received PGE1.PGE1 was administered post-LT to those with transaminases>1000 U/L in the immediate postoperative period.Demographics,post-LT treatments and/or complications,renal function,and survival were analyzed.Multivariable logistic regression analysis was performed,and a two-tailed P value<0.05 was considered statistically significant.RESULTS A total of 145 patients underwent LT,with 44(30%)receiving PGE1.Baseline patient characteristics were comparable,except the PGE1 group had significantly higher aspartate aminotransferase(AST)(1961.9 U/L±1862.3 U/L vs 878 U/L±741.4 U/L,P=0.000),alanine aminotransferase(1070.6 U/L±895 U/L vs 547.7 U/L±410 U/L,P=0.000),international normalized ratio on post-LT day 1(2±0.74 vs 1.8±0.4,P=0.03),a longer intensive care unit stay(8.1 days±11.8 days vs 3.8 days±4.6 days,P=0.003),more vasopressor use(55.53 hours±111 hours vs 16.33 hours±26.3 hours,P=0.002),and higher immediate postoperative complications(18.6%vs 4.9%,P=0.04).The PGE1 group also had a significantly higher 90-day readmission rate(29.6%vs 13.1%,P=0.02)and lower 1-year liver graft survival(87.5%vs 98.9%,P=0.005).However,30-day readmission(31.6%vs 27.4%,P=0.64),LT complications(hepatic artery thrombosis,biliary complications,rejection of liver graft,cardiomyopathy),1-year patient survival(96.9%vs 97.8%,P=0.77),overall liver graft survival,and overall patient survival were similar between the two groups(95.4%vs 93.9%,P=0.74 and 88.4%vs 86.9%,P=0.81 respectively).Although the PGE1 group had a significantly lower glomerular filtration rate(eGFR)on post-LT day 7(46.3 mL/minute±26.7 mL/minute vs 62.5 mL/minute±34 mL/minute,P=0.009),the eventual need for renal replacement therapy(13.6%vs 5.9%,P=0.09),the number of dialysis sessions(0.91 vs 0.27,P=0.13),and eGFR at 1-month(37.2 mL/minute±35.9 mL/minute vs 42 mL/minute±36.9 mL/minute,P=0.49),6-months(54.8 mL/minute±21.6 mL/minute vs 62 mL/minute±21.4 mL/minute,P=0.09),and 12-months(63.7 mL/minute±20.7 mL/minute vs 62.8 mL/minute±20.3 mL/minute,P=0.85)post-LT were similar to those in the non-PGE1 group.CONCLUSION In patients who received PGE1 for ischemia-reperfusion injury,despite immediate acute renal injury post-LT,the renal function at 1-month,6-months,and 12-months post-LT was similar compared to those without ischemiareperfusion injury.Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.
基金This work is supported by grant from Beijing Tide Pharmaceutical Co,Ltd.
文摘Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandin E1 on platelet aggregation function [ PAG (5,) PAG( m ) ], serum total protein (TP) , albumin (Al),blood urea nitrogen(BUN) ,serum creatinine(Scr) ,cholesterol(CHO), triglyceride(TG), protein in 24-hour urine (Pr/24h) and platelet account (PLT). Results: TP, Al, CHO, TG, BUN, Scr, Pr/24h, PAG(5) and PAG(m) in PNS group before treatment were significantly different from those in control group(P＜0.05, P＜0.01) while no significant difference was found for PLT. When treated with PGE1 , TP,Al,CHO, TG, Pr/24h, ADP- induced PAG(5) ,and Adr- induced PAG(5) and PAG(m) were significantly different from those before treatment (P＜0.05). Adr- induced PAG(5) and PAG(m) were significantly different. Adr- induced PAG(5) was xsitively correlated with BUN and Scr in PNS(P＜0.01). Similar correlation was found between ADP-induced PAG(5) and Al ,BUN,Scr,Pr/24h(P＜0.05), AD- induced PAG(m) and TP,CHO(P＜0.05). Conclusions: PGE1 may be an effective drug for the treatment for hypercoagulation in patients with PNS.
文摘Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neural pathways. In this review, we first briefly summarize current views on the mechanism of sensing microbial infection by the nervous system, and the roles of prostaglandin E2 （PGE2） and its receptors in fever; then we focus on the neural circuits underlying fever generation, particularly their relationship with the distribution of PGE2 receptors within the CNS. At the end, an overall neurochemical model of fever generation is presented, pointing to the direction for future studies.
基金Supported by National Natural Science Foundation, No. 30572310Hunan Natural Science Foundation, No. 05JJ 4008
文摘AIM:To study the effect of moxibustion on Zusanli or Liangmeng point on gastric mucosa injury in stress-induced ulcer rats and its correlation with the expression of heat shock protein 70 (HSP70). METHODS:Sixty healthy SD rats (30 males,30 females) were divided into control group,injury model group,Zushanli point group,Liangmeng point group. Stress gastric ulcer model was induced by binding cold stress method. Gastric mucosa ulcer injury (UI) index was calculated by Guth method. Gastric mucosa blood flow (GMBF) was recorded with a biological signal analyzer. Protein content and gene expression in gastric mucosal HSP70 were detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). Thiobarbital method was used to determine malondialdehyde (MDA) content. Gastric mucosal endothelin (ET) and prostaglandin E2 (PGE2) were analyzed by radioimmunoassay. RESULTS:High gastric mucosal UI index,high HSP70 expression,low GMBF and PGF2,elevated MDA and ET were observed in gastric mucosa of rats subjected to cold stress. Moxibustion on Zusanli or Liangmeng point decreased rat gastric mucosal UI index,MDA and ET. Conversely,the expression of HSP70,GMBF,and PGE2 was elevated in gastric mucosa after pretreatment with moxibustion on Zusanli or Liangmeng point. The observed parameters were significantly different between Zusanli and Liangmeng points. CONCLUSION:Pretreatment with moxibustion on Zusanli or Liangmeng point protects gastric mucosa against stress injury. This protection is associated with the higher expression of HSP70 mRNA and protein,leading to release of PGE2 and inhibition of MDA and ET,impairment of gastric mucosal index.
文摘AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.
基金Supported by (in part) the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence,No.MOHW105-TDU-B-212-133019
文摘AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control. RESULTS Our results showed that 20 mu mol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3 beta, and beta-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of beta-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice. CONCLUSION TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.
文摘AIM: To examine the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in rat esophageal lesions induced by reflux of duodenal contents.
基金supported by the National S&T Major Project(2017ZX10203201-002-002)
文摘Objective: To evaluate the serum Prostaglandin E2(PGE2) level in Acute-on-chronic liver failure(ACLF) and determine its predicative value for infection.Methods: From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating characteristic(ROC) curves were used to determine optimal cut-off values to predict infection.Results: Significantly higher PGE2 levels were found in patients with ACLF in comparison with healthy controls and patients with stable CHB(P < 0.000 1). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication(P < 0.000 1). ROC analysis showed that serum PGE2(area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/m L.Conclusions: Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.
基金Supported by National Natural Science Foundation of China,No.81373097.
文摘Gastric cancer accounts for the majority cancer-related deaths worldwide.Although various methods have considerably improved the screening,diagnosis,and treatment of gastric cancer,its incidence is still high in Asia,and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%.Therefore,more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer.Cyclooxygenase-2(COX-2)is considered to be the key inducible enzyme in prostaglandins(PGs)synthesis,which is involved in multiple pathways in the inflammatory response.For example,inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway.In these processes,the production of an inflammatory microenvironment promotes the occurrence of gastric cancer.Epidemiological studies have also indicated that non-steroidal antiinflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2.However,clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects,especially in the cardiovascular system.Given these side effects and low treatment efficacy,new therapeutic approaches and early screening strategies are urgently needed.Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis.However,the genetic variation analysis in these studies is incomplete and isolated,pointing out only a few single nucleotide polymorphisms(SNPs)and the risk of gastric cancer,and no comprehensive study covering the whole gene region has been carried out.In addition,copy number variation(CNV)is not mentioned.In this review,we summarize the SNPs in the whole COX-2 gene sequence,including exons,introns,and both the 5’and 3’untranslated regions.Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population.This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies,summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer,and discusses the future prospect of therapeutic intervention,which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.
文摘AIM: To examine the effect of prostaglandin E2 (PGE2) on the expression of vascular endothelial growth factor (VEGF) mRNA in the human hepatocellular carcinoma (HCC) HepG2 cells and the possible involvement of c-fos protein in this process.METHODS: Human HCC HepG2 cells were divided into three groups treated respectively with PGE2, a combination of PGE2 and c-fos antisense oligodeoxynucleotide (ASO),and PGE2 plus c-fos sense oligodeoxynudeotide (SO). The expression of VEGF mRNA in HepG2 cells after different treatments was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The relative expression level of VEGF mRNA in HepG2 cells in each group was measured.RESULTS: Administration of PGE2 resulted in an increased expression of c-fosand VEGF mRNA in HepG2 cells. The relative expression level of c-fos mRNA reached the peak at 3 h (68.4±4.7%) after PGE2 treatment, which was significantly higher than that at 0 h (20.6±1.7%, P＜0.01).Whereas, the highest expression level of VEGF mRNA was observed at 6 h (100.5±6.1%) after PGE2 treatment, which was significantly higher than that at 0 h (33.2±2.4%,P＜0.01). C-fos ASO significantly reduced PGE2-induced VEGF mRNA expression in HepG2 cells.CONCLUSION: PGE2 increases the expression and secretion of VEGF in HCC cells by activating the transcription factor c-fos, promotes the angiogenesis of HCC and plays an important role in the pathogenesis of liver cancer.
文摘Objective To investigate the effects of prostaglandin E1 (PGE1) on the progression of aristolochic acid nephropathy (AAN). Methods Twenty-four patients diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL and 4 mg/dL during September 2001 to August 2003 were randomly divided into 2 groups. All patients had ingested long dan xie gan wan con-taining aristolochic acid (0.219 mg/g) for at least 3 months. Twelve patients were injected with Alprostadil (10 μg/d for 10 days in one month, summing up to 6 months). Except for PGE1, the other therapy was same in both groups. Renal function was assessed using reciprocal serum creatinine levels (1/Scr). Results The level of Scr and serum hemoglobin (Hgb) was similar in both groups prior to therapy. During follow-up, 1/Scr levels in PGE1 group were significantly higher than control group (P < 0.01), and Hgb levels in PGE1 group were sig-nificantly increased compared with control (P < 0.05).Conclusion PGE1 can slow the progression of renal failure and increase Hgb level of AAN patient.
基金Supported by National Natural Science Foundation of China,No.81260331Key Laboratory for High-Incidence Tumor Prevention and Treatment,Ministry of Education,No.GKE2015-ZZ05
文摘AIM to determine whether cyclooxygenase-2(COX-2) and prostaglandin E1 receptor(EP1) contribute to disease and whether they help predict prognosis.METHODS We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma(HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffinembedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were determined.RESULTS Factors associated with poor overall survival(OS) were alpha-fetoprotein > 400 ng/m L, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues(Edmondson grade Ⅰ-Ⅱ) than in poorly differentiated tissues(Edmondson grade Ⅲ-Ⅳ)(P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue(P = 0.001).CONCLUSION COX-2 expression appears to be linked to early HCC events(initiation), while EP1 receptor expression may participate in tumor progression and predict survival.
基金Supported by the National Ministry of Health and Welfare
文摘AIM： To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanoltreated rat＇s stomach to naproxen （NAP）. METHODS： Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP （50 mg/kg） was administered. DA-9601 was admin- istered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index （mm2）, histologic change and to determine mucosal levels of malondialdehyde （MDA）, prostaglandin E2 （PGE2）, glutathione （GSH） and myeloperoxidase （MPO）. RESULTS： Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in NDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAR DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats （P〈0.05）, with reduction in mucosal MDA and MPO levels. CONCLUSION： These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved.
文摘In order to evaluate the effects and mechanisms of celecoxib in inhibiting proliferation and inducing apoptosis on human pancreatic carcinoma cells, the anti-proliferative effect was measured by using methabenzthiazuron (MTT) assay. Cell cycle and apoptosis were analyzed by using flow cytometry (FCM), and the PGE 2 levels in the supernatant of cultured pancreatic carcinoma cells were quantitated by enzyme-linked immunoabsordent assay (ELISA). Our results showed that celecoxib suppressed the production of PGE 2 and inhibited the growth of JF-305 cells, and the anti-proliferative effect of celecoxib could be abolished by addition of PGE 2. FCM revealed that celecoxib could inhibit proliferation and induce apoptosis by G 1-S cell cycle arrest. It was concluded that cyclooxygenase-2 specific inhibitor celecoxib could inhibit proliferation and induced apoptosis of human pancreatic carcinoma cells via suppression of PGE 2 production in vitro.
基金Supported by the National Science Council of Taiwan (NSC 92-2320-B-038-027) the Min-Sheng Healthcare (93MSH-TMU-006)
文摘AIM: To investigate the effect of lipopolysaccharide (LPS)on the diarrheogenic activity, gastrointestinal transit (GIT),and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastrointestinal functions of endotoxin-treated mice.METHODS: Diarrheogic activity, GIT, and intestinal fluid content as well as nitric oxide and PGE2 products were measured after intraperitoneal administration of LPS in mice.RESULTS: LPS dose-dependently accumulated abundant fluid into the small intestine, induced diarrhea, but decreased the GIT. Both nitric oxide and PGE2 were found to increase in LPS-treated mice. Western blot analysis indicated that LPS significantly induced the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in mice intestines. Pretreatment with NG-nitro-L-arginine-methyl ester (L-NAME, a non-selective NOS inhibitor) or indomethacin (an inhibitor of prostaglandin synthesis) significantly attenuated the effects of LPS on the diarrheogenic activity and intestine content, but reversed the GIT.CONCLUSION: The present study suggests that the pathogenesis of LPS treatment may mediate the stimulatory effect of LPS on nitric oxide and PGE2 production and NO/prostaglandin pathway may play an important role on gastrointestinal function.
基金supported by the Norwegian Research Council grant no.241011the Norwegian Dental Depot Fund for Dental Research
文摘Streptococcus mitis （S. mitis） is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction with the host. We used examination of its transcriptional regulation in oral keratinocytes to elucidate some of its potential roles in the oral cavity. Transcription factor analysis of oral keratinocytes predicted S. mitis.mediated activation of aryl hydrocarbon receptor （AhR）, Activation and functionality of AhR was confirmed through nuclear translocation determined by immunofluorescence microscopy and real-time polymerase chain reaction with reverse transcription analysis of CYPIA1, the hallmark gene for AhR activation. Addition of Streptococcus mutans or Streptococcus gordonfi did not induce CYPIA1 transcription in the keratinocyte cultures. Introduction of an AhR-specific inhibitor revealed that S. mitis-mediated transcription of CXCL2 and CXCL8 was regulated by AhR. Elevated levels of pmstaglandin E2 （enzyme-linked immunosorbent assay） in supernatants from S. mitis-treated oral epithelial cells were also attenuated by inhibition of AhR activity. The observed AhR-regulated activities point to a contribution of S. mitis in the regulation of inflammatory responses and thereby to wound healing in the oral cavity. The concept that the oral commensal microbiota can induce AhR activation is important, also in view of the role that AhR has in modulation of T-cell differentiation and as an anti-inflammatory factor in macrophaees.
文摘AIM:To investigate whether microsomal prostaglandin E synthase-1 (mPGES-1) expression in hepatocellular carcinoma (HCC) and in non-cancerous liver affects HCC prognosis after hepatectomy. METHODS: The relationship between patient clinical prof iles, tumor factors, surgical determinants, and mPGES-1 expression and the recurrence-free survival rate were examined in 64 patients who underwent curative hepatectomy between March 2003 and December 2006. RESULTS: The scores for mPGES-1 expression were higher in well differentiated and moderately differentiated HCC tissues than in poorly differentiated HCC tissues (well differentiated, 5.1 ± 2.7; moderately differentiated, 5.1 ± 1.7; poorly differentiated, 3.0 ± 1.8). In noncancerous liver tissues, the mPGES-1 levels were higher in injured liver tissues than in normal tissues. Cirrhotic livers had higher mPGES-1 levels than livers with chronic hepatitis (normal livers, 3.3 ± 0.7; chronic hepatitic livers, 5.4 ± 1.9; cirrhotic livers, 6.4 ± 1.6). A univariate analysis revealed that the recurrence-free survival rate was signif icantly lower in patients with vascular invasion,a higher mPGES-1 level in non-cancerous liver tissue,a larger tumor diameter (≥5 cm), and a lower serum albumin level (≤3.7 g/dL). The mPGES-1 expression in HCC tissues did not correlate well with postoperative recurrence. A multivariate analysis demonstrated that the presence of vascular invasion and higher mPGES-1 levels were statistically significant independent predictors for early postoperative recurrence of HCC.CONCLUSION: Increased mPGES-1 expression in noncancerous liver tissues is closely associated with the early recurrence of HCC after curative resection.
