Prostaglandin E1 administration post liver transplantation and renal outcomes:A retrospective single center experience

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.

Intra-arterial lipo-prostaglandin E1 infusion for arterial spasm in liver transplantation:A case report

BACKGROUND Hepatic artery obstruction is a critical consideration in graft outcomes after living donor liver transplantation.We report a case of diffuse arterial vasospasm that developed immediately after anastomosis and was managed with an intra-arterial infusion of lipo-prostaglandin E1(PGE1).CASE SUMMARY A 57-year-old male with hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma underwent ABO-incompatible living donor liver transplant.The grafted hepatic artery was first anastomosed to the recipient’s right hepatic artery stump.However,the arterial pulse immediately weakened.Although a new anastomosis was performed using the right gastroepiploic artery,the patient’s arterial pulse rate remained poor.We attempted angiographic intervention immediately after the operation;it showed diffuse arterial vasospasms like‘beads on a string’.We attempted continuous infusion of lipo-PGE1 overnight via an intra-arterial catheter.The next day,arterial flow improved without any spasms or strictures.The patient had no additional arterial complications or related sequelae at the time of writing,1-year post-liver transplantation.CONCLUSION Angiographic evaluation is helpful in cases of repetitive arterial obstruction,and intra-arterial infusion of lipo-PGE1 may be effective in treating diffuse arterial spasms.

Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E_2 and cytokines

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.

Thymoquinone suppresses migration of Lo Vo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation

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.

Elevated serum prostaglandin E2 predicts the risk of infection in hepatitis B virus-related acute-on-chronic liver failure patients

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.

Effect of c-fos antisense probe on prostaglandin E_2-induced upregulation of vascular endothelial growth factor mRNA in human liver cancer cells

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.

EFFECTS OF PROSTAGLANDIN E1 ON THE PROGRESSION OF ARISTOLOCHIC ACID NEPHROPATHY

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.

Effect of lipopolysaccharide on diarrhea and gastrointestinal transit in mice: Roles of nitric oxide and prostaglandin E_2

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.

Effects of prostaglandin E combined with continuous renal replacement therapy on septic acute kidney injury

BACKGROUND The effects of prostaglandin E(PGE)combined with continuous renal replacement therapy(CRRT)on renal function and inflammatory responses in patients with septic acute kidney injury(SAKI)remain unclear.AIM To investigate the effects of PGE combined with CRRT on urinary augmenter of liver regeneration(ALR),urinary Na+/H+exchanger 3(NHE3),and serum inflammatory cytokines in patients with SAKI.METHODS The clinical data of 114 patients with SAKI admitted to Yichang Second People's Hospital from May 2017 to January 2019 were collected.Fifty-three cases treated by CRRT alone were included in a control group,while the other 61 cases treated with PGE combined with CRRT were included in an experimental group.Their urinary ALR,urinary NHE3,serum inflammatory cytokines,renal function indices,and immune function indices were detected.Changes in disease recovery and the incidence of adverse reactions were observed.The 28-d survival curve was plotted.RESULTS Before treatment,urinary ALR,urinary NHE3,blood urea nitrogen(BUN),serum creatinine(SCr),CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio in the control and experimental groups were approximately the same.After treatment,urinary ALR and NHE3 decreased,while BUN,SCr,CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio increased in all subjects.Urinary ALR,urinary NHE3,BUN,and SCr in the experimental group were significantly lower than those in the control group,while CD3+T lymphocytes,CD4+T lymphocytes,and CD4+/CD8+T lymphocyte ratio were significantly higher than those in the control group(P<0.05).After treatment,the levels of tumor necrosis factor-α,interleukin-18,and high sensitivity C-reactive protein in the experimental group were significantly lower than those in the control group(P<0.05).The time for urine volume recovery and intensive care unit treatment in the experimental group was significantly shorter than that in the control group(P<0.05),although there was no statistically significant difference in hospital stays between the two groups.The total incidence of adverse reactions did not differ statistically between the two groups.The 28-d survival rate in the experimental group(80.33%)was significantly higher than that in the control group(66.04%).CONCLUSION PGE combined with CRRT is clinically effective for treating SAKI,and the combination therapy can significantly improve renal function and reduce inflammatory responses.

Protective effects of prostaglandin E1 perfusion againstspinal cord ischemia-reperfusion injury in a rabbit model

BACKGROUND： Prostaglandin E1 （PGE1） is known to be protective in ischemia-reperfusion of heart, lung,renal, and liver tissue. It still remains to be determined whether PGE1 exhibits similar protection against spinal cord ischemia-reperfusion injury in a rabbit model. OBJECTIVE： To observe the large, ventral horn, motor neurons of the spinal cord, as well as limb function, and to investigate whether perfusion of PGE1 exhibits protective effects against spinal cord ischemia-reperfusion injury in a rabbit model. DESIGN, TIME AND SETTING： Controlled observation. The experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between June and October 2007. MATERIALS： Twenty male, New Zealand white rabbits, weighing 2.0 kg and of mixed gender, were used in the present study. The following chemicals and compounds were used： prostaglandin E1 injectable powder,as well as malondialdehyde and ATPase kits. Animal intervention was in accordance with animal ethical standards. METHODS： We separated rabbits into control and experimental groups randomly, with 10 rabbits in each group. Rabbits were used as spinal cord ischemia models by segmentally cross-clamping the infrarenal aorta. The control group was subsequently perfused for five minutes with blood and saline solution, and the experimental group was perfused for 5 minutes with blood and saline solution containing PGE1 （100 ng/kg/min）. MAIN OUTCOME MEASURES： The neurological function of the hind limbs was assessed 12, 24, and 48 hours after model establishment. All animals were sacrificed and spinal cords were harvested for histological analyses. The large motor neurons in the ventral horn of L1-7 were observed by inverted microscope. RESULTS： All 20 rabbits were included in the final analysis, without any loss. In the ventral horn of the L5-7 segments, there were more large motor neurons that appeared viable in the experimental group than the control group （P 〈 0.05）. The scores of hind limb functions were greater in the experimental group after 12, 24, and 48 hours （P 〈 0.01）. CONCLUSION： Perfusion of PGE1 reduced the amount of neuronal damage in the spinal cord ischemia-reperfusion injury rabbit model. These results correlated with increased numbers large motor neurons in the ventral horn of the spinal cord, as well as improved hind limb function.

Does perioperative prostaglandin E1 affect survival of patients with esophageal cancer?

AIM: To detect the effect of intraoperative prostaglandin E1 (PGE1) infusion on survival of esophagectomized patients due to cancer. METHODS: In this preliminary study, a double blinded placebo based clinical trial was performed. Thirty patients with esophageal cancer scheduled for esophagectomy via the transthoracic approach were randomized by a block randomization method, in two equal groups: PGE1 group - infusion of PGE1 (20 ng/kg per minute) in the operating room and placebo group - saline 0.9% with the same volume and rate. The infusion began before induction of anesthesia and finished just before transfer to the intensive care unit. The patients, anesthetist, intensive care physicians, nurses and surgeons were blinded to both study groups. All the patients were anesthetized with the same method. For postoperative pain control, a thoracic epidural catheter was placed for all patients before induction of anesthesia. We followed up the patients until October 2010. Basic characteristics, duration of anesthesia, total surgery and thoracotomy time, preoperative hemoglobin, length of tumor, grade of histological differentiation, disease stage, number of lymph nodes in the resected mass, number of readmissions to hospital, total duration of readmission and survival rates were compared between the two groups. Some of the data originates from the historical data reported in our previous study. We report them for better realization of the follow up results. RESULTS: The patients’ characteristics and perioperative variables were compared between the two groups. There were no significant differences in age (P = 0.48), gender (P = 0.27), body mass index (P = 0.77), American Society of Anesthesiologists physical status more than?I?(P = 0.71), and smoking (P = 0.65). The PGE1 and placebo group were comparable in the following variables: duration of anesthesia (277 ± 50 vs 270 ± 67, P = 0.86), duration of thoracotomy (89 ± 35 vs 96 ± 19, P = 0.46), duration of operation (234 ± 37 vs 240 ± 66, P = 0.75), volume of blood loss during operation (520 ± 130 vs 630 ± 330, P = 0.34), and preoperative hemoglobin (14.4 ± 2 vs 14.7 ± 1.9, P = 0.62), respectively. No hemodynamic complications requiring an infusion of dopamine or cessation of the PGE1 infusion were encountered. Cancer variables were compared between the PGE1 and placebo group. Length of tumor (11.9 ± 3 vs 12.3 ± 3, P = 0.83), poor/undifferentiated grade of histological differentiation [3 (20%) vs 3 (20%), P = 0.78], disease stage III [5 (33.3%), 4 (26.7%), P = 0.72] and more than 3 lymph nodes in the resected mass [3 (20%) vs 2 (13.3%), P = 0.79] were similar in both groups. All the patients were discharged from hospital except one patient in the control group who died because of a post operative myocardial infarction. No life threatening postoperative complication occurred in any patient. The results of outcome and survival were the same in PGE1 and placebo group: number of readmissions (2.1 ± 1 vs 1.9 ± 1, P = 0.61), total duration of readmission (27 ± 12 vs 29 ± 12, P = 0.67), survival rate (10.1 ± 3.8 vs 9.6 ± 3.4, P = 0.71), overall survival rate after one year [8 (53.3%) vs 7 (47%), P = 0.72], overall survival rate after two years [3 (20%) vs 3 (20%), P = 0.99], and overall survival rate after three years [0 vs 1 (6.7%), P = 0.99], respectively. CONCLUSION: In conclusion, PGE1 did not shorten or lengthen the survival of patients with esophageal cancer. Larger studies are suggested.

The effect of prostaglandin E_1 on recovery of early renal graft functions after transplantation

Objective To investigate the effect of prostaglandin E1 (PGE1) on recovery of early renal graft functions after transplantation. Methods One hundred and seven patients after renal transplantation were allocated in the treated group, and treated by conventional treatment with injection of 10 μg prostaglandin E1 additionally twice a day for 14 days. And eighty-eight patients who received conventional treatment alone after renal transplantation at the corresponding period were allocated in the control group. Indexes of the two groups, including incidence of delayed graft function and acute rejection reaction, volume of urine, serum certaintie (SCr), endogenous certainties clearance rate (CCr), the blood flow resistance in graft as well as blood viscosity (BV), and platelet aggregation rate (PAR), were determined. Results The urinary volume and endogenous certainties clearance rate of the treated group were significantly higher, but the level of SCr, incidence of renal function recovery retardation, BV, PAR and blood flow resistance in graft were significantly lower than those of the control group (P<0.05). The difference of incidence of acute rejection reaction between the two groups was insignificant (P>0.05). Conclusion Prostaglandin E1 can improve blood microcirculation and decrease the incidence of renal function recovery retardation. These effects are helpful for recovery of renal function after renal transplantation.

Expression of prostaglandin E_2 receptors in rat hippocampus

BACKGROUND: Prostaglandin E2 (PGE2) can directly regulate toxic injury of hippocampal neurons through participation by its receptor. Increase of excitability of hippocampal membrane and long-term synaptic elasticity are closely related to PGE2, PGD2 and PGF2A. This suggests that PGE2 may be a key molecule of neuronal signal passage and regulate the existence of neurons through its receptor. However, which isoforms of PGE2 receptor expressing in hippocampal neurons is still unclear. OBJECTIVE: To research the subtype expression of PGE2 receptor in hippocampus of rats through mRNA transcription and protein interpretation. DESIGN: Animal studies with random, control and operator and designer double-blind methods. SETTING: University of South Carolina, Animal Center. MATERIALS: Sprague-Dawley rats, aged 12 weeks, weighing 200 g, females 48 and males 48, were selected from Animal Center in South Carolina University. Tri ReagentTM kit was provided by Molecular Research Center, USA. METHODS: The experiment was carried out in Animal Center in South Carolina University from January to December 2005. The expression of the PGE2 receptors was profiled and compared in rat hippocampus using real-time RT-PCR and Western-blot techniques. MAIN OUTCOME MEASURES: Expression of PGE2 receptors in various isoforms of hippocampal neurons of rats. RESULTS: mRNAs of all four EP1-4 subtypes were detected in the hippocampus. Western-blot data showed consistently detectable bands at approximately Mr 50 000 of EP1, Mr 40 000 and Mr 52 000 of EP2, Mr 45 000, Mr 57 000 and Mr 105 000 of EP3, and Mr 46 000 of EP4. CONCLUSION: Identifying four subtypes of EPs heterogeneously expresses in the hippocampus.

INHIBITORY EFFECT OF ELECTROACUPUNCTURE ON FEVER INDUCED BY LIPOPOLYSACCHARIDE, INTERLEUKIN-1βAND PROSTAGLANDIN E_2 IN RATS

The effect of electroacupuncture (EA) on fever induced by either lipopolysaccharide (LPS), Interleukin-1β(IL-1β) or Prostaglandin E2(PGE2 ) was examined in SD rats in this study. EA stimulation (successive stimulation output; voltage intensity, 1 to 4 V; frequency, 1 Hz) was applied to bilateral equvalent Quchi (LI 11 ) acupoints for 30 min. Intraperitoneal injection of LPS (0111: B 4) at a single dose of 100 μg/kg caused high rectal temperature in rats, which was remarably sup pressed by EA either given simultaneously or 2 h after LPS injection. No difference in reduction of fever was found between two groups of rats treated by EA at different times. The rats that received adIninistration of hrIL-1β(2ng) or PGE2(3μg) into the prooptic area (POA) developed the acute and high fevers. The temperature in both cases was significantly decreased after EA stimulation. EA also partially inhibited the fever caused by intravenous injection of 0. 5μg/kg IL-1β. The they temperature increased within 1℃ in the rats that got intravenous injection of PGE2 (1. 5mg/kg), and EA did not present strong inhibitory effect on it. The present results demonstrate that EA possesses an antipyretic effect in rats and suggest that which may attribute to the suppression of the actions of IL-1β and/or PGE2 in the development of fever.

Mating behaviors in ovoviviparous black rockfish(Sebastes schlegelii):molecular function of prostaglandin E2 as both a hormone and pheromone

Prostaglandins(PGs)are profound hormones in teleost sexual behavior,especially in mating.PGs act as pheromones that affect the olfactory sensory neurons of males,inducing the initiation of a series of mating behaviors.However,the molecular mechanism by which PGs trigger mating behavior in ovoviviparous teleosts is still unclear.In the present study,we employed the ovoviviparous black rockfish(Sebastes schlegelii),an economically important marine species whose reproductive production is limited by incomplete fertilization,as a model species.The results showed that when the dose of PGE2 was higher than 10 nmol/L,a significant(P<0.05)increase in mating behaviors was observed.Dual-fluorescence in situ hybridization indicated that PGE2 could fire specific neurons in different brain regions and receptor cells in the olfactory sac.After combining with specific neurons in the central nervous system(CNS),a series of genes related to reproduction are activated.The intracerebroventricular administration of PGE_(2) significantly increased lhb levels(P<0.05)in both sexes.Moreover,steroidogenesis in gonads was also affected,inducing an increase(P<0.05)in E_(2) levels in males and T levels in females.PGE_(2) levels were also increased significantly(P<0.05)in both sexes.The present study revealed that PGE2 can activate mating behavior in black rockfish in both hormone and pheromone pathways,leading to variations in sex steroid levels and activation of reproductive behaviors.Our results provide not only novel insight into the onset of mating behaviors in ovoviviparous teleosts but also solutions for the incomplete fertilization caused by natural mating in cage aquaculture.

Update on the pathological roles of prostaglandin E_(2) in neurodegeneration in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor neurons.The pathogenesis of ALS remains largely unknown;however,inflammation of the spinal cord is a focus of ALS research and an important pathogenic process in ALS.Prostaglandin E_(2)(PGE_(2))is a major lipid mediator generated by the arachidonic-acid cascade and is abundant at inflammatory sites.PGE_(2)levels are increased in the postmortem spinal cords of ALS patients and in ALS model mice.Beneficial therapeutic effects have been obtained in ALS model mice using cyclooxygenase-2 inhibitors to inhibit the biosynthesis of PGE_(2),but the usefulness of this inhibitor has not yet been proven in clinical trials.In this review,we present current evidence on the involvement of PGE_(2)in the progression of ALS and discuss the potential of microsomal prostaglandin E syn-thase(mPGES)and the prostaglandin receptor E-prostanoid(EP)2 as therapeutic targets for ALS.Signaling pathways involving prostaglandin receptors mediate toxic effects in the central nervous system.In some situations,however,the receptors mediate neuroprotective effects.Our recent studies demonstrated that levels of mPGES-1,which catalyzes the final step of PGE_(2)biosynthesis,are increased at the early-symptomatic stage in the spinal cords of transgenic ALS model mice carrying the G93A variant of superoxide dismutase-1.In addition,in an experimental motor-neuron model used in studies of ALS,PGE_(2)induces the production of reactive oxygen species and subsequent caspase-3-de-pendent cytotoxicity through activation of the EP2 receptor.Moreover,this PGE_(2)-induced EP2 up-regulation in motor neurons plays a role in the death of motor neurons in ALS model mice.Further understanding of the pathophysiologi-cal role of PGE_(2)in neurodegeneration may provide new insights to guide the development of novel therapies for ALS.

Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene:Hypotheses and conundrums

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.

Roles of the prostaglandin E2 receptors EP subtypes in Alzheimer’s disease

Neuroinflammation has always been of concern in the pathogenesis of Alzheimer’s disease （AD）. As a major inflammatory mediator, prostaglandin E2 （PGE2） plays an important role in the inflammatory process of AD. Up to now, there is still controversy on the neuroprotective or neurotoxic role of PGE2. However, the role of PGE2 in neurodegeneration may be far more complex, due to the 4 EP receptor subtypes. This article aims to summarize the relationship between PGE2 receptor EP subtypes and AD. It is believed that a better understanding of the PGE2 receptor EP subtypes may help to clarify the relation between inflammation and AD, and to develop novel therapeutic strategies targeting specific EP receptor for AD treatment.

血清KYNA、EP4在老年急性心肌梗死患者中表达水平及其与心肌损伤预后的相关性

目的探讨老年急性心肌梗死(AMI)患者血清犬尿喹啉酸(KYNA)、E-前列腺素受体4(EP4)表达与心肌损伤预后的相关性。方法选取长江大学附属仙桃市第一人民医院收治的87例老年AMI患者作为试验组,同时选择80例老年健康体检者作为对照组,试验组依据预后情况分为预后良好组(75例)及预后不良组(12例)。检测血清KYNA、EP4及心肌酶指标cTnI、CK-MB、CK表达水平;血清KYNA、EP4与心肌酶指标的相关性采用Pearson相关性分析;KYNA、EP4水平与老年AMI患者预后的关系采用Kaplan-Meier生存曲线分析;老年AMI患者预后不良的影响因素采用多因素COX回归分析。结果试验组TG、LDL-C及TC高于对照组(P<0.05),试验组患者血清KYNA及心肌酶指标cTnI、CK-MB及CK的表达水平升高,EP4表达水平降低(P<0.05);相关性分析显示,血清KYNA与心肌酶指标呈正相关,EP4与心肌酶指标呈负相关;血清KYNA低表达患者3年生存率高于高表达患者,EP4高表达患者3年生存率高于低表达患者。预后不良组cTnI、CK-MB、CK及KYNA水平高于预后良好组,EP4水平低于预后良好组(P<0.05),KYNA、EP4是AMI预后不良的影响因素(P<0.05)。结论老年AMI患者血清KYNA表达水平升高,血清EP4表达水平降低,二者与患者心肌损伤的预后相关。

老年帕金森病患者外周血、胆红素、前列腺素E表达与疾病分级、快速眼动睡眠障碍的相关性

目的 探讨老年帕金森病(PD)患者外周血神经丝轻链蛋白(NFL)、胆红素、前列腺素E表达与疾病分级、快速眼动睡眠障碍的相关性。方法 选取2020年1月至2022年10月在商洛市中心医院神经内科诊治的106例老年PD患者为研究对象,根据是否出现快速眼动睡眠障碍分为睡眠正常组和睡眠障碍组。收集患者的临床资料,比较不同疾病分级患者外周血NFL、胆红素、前列腺素E表达的区别,使用单因素和多因素Logistic回归分析外周血NFL、胆红素、前列腺素E表达、疾病分级及其他因素对老年PD患者快速眼动睡眠障碍发生的影响并构建患者睡眠障碍发生的风险预测模型,使用受试者工作特征(ROC)曲线评价该模型的预测性能。结果 不同疾病分期患者多周血NFL、胆红素及前列腺素E比较结果显示,早期组NFL及前列腺素E2均显著低于中晚期组,总胆红素显著高于中晚期组(^(均)P<0.05)。其中睡眠正常组41例(38.68%),睡眠障碍组65例(61.32%),多因素分析结果显示,两组患者NFL(OR=1.340,95%CI=1.035~1.736,P=0.027)、前列腺素E2 (OR=1.141,95%CI=1.052~1.237,P=0.001)、汉密尔顿焦虑量表(HAMA)(OR=1.378,95%CI=1.084~1.752,P=0.009)、汉密尔顿抑郁量表(HAMD)(OR=1.398,95%CI=1.092-1.790,P=0.008)为老年PD患者快速眼动睡眠障碍发生的独立影响因素(^(均)P<0.05)。在此基础上建立风险预测模型,模型公式:Logit(P)=-34.469+0.293×NFL+0.132×前列腺素E2+0.321×HAMA+0.335×HAMD。其ROC曲线下面积为0.992,95%CI:0.981~1.000,敏感度为0.969,特异度为0.951,Youden指数为0.920。结论 老年PD患者外周血NFL及前列腺素E表达均是其快速眼动睡眠障碍发生的独立影响因素,疾病分级及总胆红素未能纳入模型,可能与其他数据的干扰有关。