Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate trau...Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.展开更多
Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotectiv...Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.展开更多
BACKGROUND Methanol is a highly toxic,non-potable alcohol.Outbreaks of methanol toxicity occur due to its fraudulent addition to alcoholic beverages as a cheaper substitute for ethanol.Recently,alongside the coronavir...BACKGROUND Methanol is a highly toxic,non-potable alcohol.Outbreaks of methanol toxicity occur due to its fraudulent addition to alcoholic beverages as a cheaper substitute for ethanol.Recently,alongside the coronavirus disease 2019(COVID-19)pandemic,rumors circulated on social media that consuming alcohol can prevent or cure the virus,leading to a COVID-19 and methanol-induced optic neuropathy(MON)syndemic.AIM To investigate the impact of erythropoietin(EPO)on the outcomes of patients diagnosed with MON.METHODS In this prospective study,105 patients presenting with acute bilateral visual loss secondary to methanol intoxication were enrolled from March to May 2020 at Farabi Eye Hospital.A comprehensive ocular examination was conducted for all participants.Recombinant human EPO and methylprednisolone were administered intravenously to all patients for three consecutive days.RESULTS The mean age of the participants was 39.9 years(±12.6).Ninety-four patients were male and eleven were female.The mean pre-treatment best corrected visual acuity(BCVA)improved from 2.0±0.86 to 1.39±0.69 logarithm of the minimum angle of resolution post-treatment(P<0.001),with significant improvement observed in all age categories and genders(P<0.001).Visual acuity improvement was also significant regardless of whether the patient presented before or after 72 h(P<0.001),and the post-treatment BCVA remained significant at all monthly follow-up visits(P<0.001).CONCLUSION EPO and methylprednisolone therapy have been shown to be effective in improving visual outcomes in patients with MON when administrated within the first month of exposure.Public awareness efforts are necessary to prevent further outbreaks of methanol toxicity in the current COVID-19 era.展开更多
BACKGROUND Heart and kidney dysfunction frequently coexist in patients with acute heart failure due to the overlap between these two organ systems.Cardiorenal syndrome(CRS)results from pathology occurring in the heart...BACKGROUND Heart and kidney dysfunction frequently coexist in patients with acute heart failure due to the overlap between these two organ systems.Cardiorenal syndrome(CRS)results from pathology occurring in the heart and kidneys along with the consequences of dysfunction in one organ contributing to dysfunction in the other and vice versa.AIM To evaluate the use of erythropoietin(EPO)in patients with CRS and its effects on hemoglobin(Hb),major cardiovascular(CV)events,and hospitalization rates.METHODS On February 24,2022,searches were conducted using PubMed,MEDLINE,and EMBASE,and 148 articles were identified.A total of nine studies were considered in this systematic review.We assessed the included articles based on the National Heart,Lung,and Blood Institute quality assessment tools for controlled intervention and observational cohort or cross-sectional studies.An assessment of bias risk was conducted on the chosen studies,and data relevant to our review was extracted.RESULTS The systematic review of these studies concluded that most existing literature indicates that EPO improves baseline Hb levels and decreases myocardial remodeling and left ventricular dysfunction without reducing CV mortality.In addition,the effect of EPO on the hospitalization rate of patients with CRS needs to be further studied since this relationship is unknown.Future studies,such as randomized controlled clinical trials and prospective cohort studies,should be conducted to enhance the literature on the potential of EPO therapy in patients with CRS.CONCLUSION Our systematic review suggests that EPO therapy may have a significant role in managing CRS.The review highlights the potential benefits of EPO in improving baseline Hb levels,reducing the risk of major CV events,improving cardiac remodeling,myocardial function,New York Heart Association class,and B-type natriuretic peptide levels.However,the effect of EPO treatment on hospitalization remains unclear and needs further exploration.展开更多
Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based b...Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based biological markers for Blood-enriching Chinese herbs, we investigate the effect of 11 commonly used Blood-enriching herbs on erythropoietin (EPO) production in HepG2 cells. Herbs for nourishing Yin were tested for determining the specificity of Blood-enriching herbs in inducing EPO production. In addition, the effects of Blood-enriching herbs on nitric oxide (NO) production in both HepG2 cells and human umbilical vein endothelial cells (HUVECs) were also investigated. The results indicated that methanolic extracts of Blood-enriching herbs (but not Yin-nourishing herbs) showed characteristic pharmacological activity in inducing EPO production in HepG2 cells and NO release in HUVECs. The experimental findings, therefore, support the use of cell-based EPO production and NO release as biological markers for Blood-enriching Chinese tonifying herbs.展开更多
The oxidative stress response plays an important role in the occurrence and development of diabetic kidney disease(DKD).It has become a new treatment target for DKD.In the current study,the effects of carbamylated ery...The oxidative stress response plays an important role in the occurrence and development of diabetic kidney disease(DKD).It has become a new treatment target for DKD.In the current study,the effects of carbamylated erythropoietin(CEPO)on renal oxidative stress and damage in diabetic rats were examined.Thirty Sprague Dawley rats were intraperitoneally administered with 60 mg/kg streptozotocin to establish the diabetes model.The diabetic rats were randomly allocated into 4 groups(n=6 each):diabetes model group(DM group),DM+CEPO treatment group(DC group),DM+CEPO+EPO receptor(EPOR)blocking peptide treatment group(DCEB group),and DM+CEPO+CD131 blocking peptide treatment group(DCCB group).Meanwhile,a normal control group(NC group,n=6)was set up.Kidney tissues and blood samples were obtained for evaluation of oxidative stress and renal function.The results showed that diabetic rats exhibited increased oxidative stress in the kidney and early pathological changes associated with DKD.Treatment with CEPO reduced oxidative stress and attenuated renal dysfunction.However,diabetic rats treated with the combination of CEPO and EPOR blocking peptide or CD131 blocking peptide showed increased oxidative stress and reduced renal function when compared with CEPO treatment alone group.These results suggested that CEPO can protect against kidney damage in DKD by inhibiting oxidative stress injury via EPOR-CD131 heterodimers.展开更多
Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapopto...Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progerdtor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were pos-让ive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors.展开更多
Some in vitro experiments have shown that erythropoietin(EPO) increases resistance to apoptosis and facilitates neuronal survival following cerebral ischemia.However,results from in vivo studies are rarely reported.Pe...Some in vitro experiments have shown that erythropoietin(EPO) increases resistance to apoptosis and facilitates neuronal survival following cerebral ischemia.However,results from in vivo studies are rarely reported.Perfusion-weighted imaging(PWI) and diffusion-weighted imaging(DWI) have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore,we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion.To validate this hypothesis,we established a rat model of focal cerebral ischemia/reperfusion injury,and treated with intra-cerebroventricular injection of EPO(5,000 U/kg) 20 minutes before injury.Brain tissue in the ischemic injury zone was sampled using MRI-guided localization.The relative area of abnormal tissue,changes in PWI and DWI in the ischemic injury zone,and the number of apoptotic cells based on Td T-mediated d UTP-biotin nick end-labeling(TUNEL) were assessed.Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI,increases cerebral blood volume,and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion.The experiment provides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.展开更多
AIM:To investigate the protective effect of erythropoietin (Epo) against ischemia-reperfusion injury (IR/I) following the Pringle maneuver (PM),in comparison with conventional steroid administration in a prospective r...AIM:To investigate the protective effect of erythropoietin (Epo) against ischemia-reperfusion injury (IR/I) following the Pringle maneuver (PM),in comparison with conventional steroid administration in a prospective randomized trial. METHODS:Patients were randomized by age, sex, diagnosis, and surgical method, and assigned to three groups:(1) A steroid group (STRD, n= 9) who received 100 mg of hydrocortisone before PM, and on postoperative days 1, 2 and 3, followed by tapering until postoperative day 7; (2) An EPO1 group (n=10) who received 30 000 U of Epo before the PM and at the end of surgery; and (3) An EPO2 group (n=8) who received 60 000 U of Epo before the PM. Hemoglobin (Hb), hematocrit (Ht), aspartate aminotransferase (AST), alanine transaminase (ALT),lactate dehydrogenase (LDH), lactate, interleukin-6 (IL-6),and tumor necrosis factor(TNF)-α were measured before and just after (Day 0) surgery, and on postoperative days 1, 3, 7 and 14. RESULTS: There were no increases in Hb and Ht in the EPO1 and EPO2 groups. AST was signif icantly lower in EPO1 than in STRD on Day 0 (P=0.041), and lower in EPO1 than in STRD and EPO2 on Day 1 (P=0.018). ALT was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.020) and Day 1 (P=0.004). There were no signif icant inter-group differences in the levels of LDH and lactate. IL-6 was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.0036) and Day 1 (P=0.0451). TNF-α was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.0006) and Day 1 (P<0.0001). Furthermore, hospitalization was signif icantly shorter in EPO1 and EPO2 than in STRD.CONCLUSION:Epo has greater potential than steroids to ameliorate IR/I after the PM. Epo at a dose of 30000 U, administered before PM and just after surgery, yields better results.展开更多
BACKGROUND:During hepatectomy,a period of ischemia and restoration of the blood supply can result in hepatic ischemia-reperfusion injury(IRI).Current research indicates that erythropoietin(EPO)has a protective effect ...BACKGROUND:During hepatectomy,a period of ischemia and restoration of the blood supply can result in hepatic ischemia-reperfusion injury(IRI).Current research indicates that erythropoietin(EPO)has a protective effect in animal models of cerebral ischemia,myocardial infarction,and renal IRI.However there is lack of research into the role of EPO in hepatic IRI.This study aimed to explore the role of EPO in hepatic IRI and its possible mechanism of action. METHODS:Thirty male Sprague-Dawley rats were divided into three groups:(1)ten rats in the experimental group were given 1000 IU/kg EPO one day before the operation;(2)ten rats in a control group were given normal saline preoperatively as a placebo;and(3)ten rats served as a sham-operated group.Hepatic IRI was induced by occluding the hepatic arteries of the three cephalad hepatic segments and the portal vein for about 45 minutes,while in the sham- operated group only laparotomy was performed.The levels of ALT and AST were tested 24 hours pre-and post-operation. All rats were sacrificed 24 hours after the operation to assess the pathologic changes in the liver and measure the expression of heme oxygenase-1(HO-1)through Western blotting and RT-PCR. RESULTS:Hepatic IRI was markedly mitigated in the experimental group as compared with the control group. Moreover,the expression of HO-1 at the level of both transcription and protein increased prominently(P<0.05) in the experimental group. CONCLUSION:These results demonstrate that EPO can up-regulate HO-1 in liver tissues and accordingly decrease hepatic injury through its anti-inflammatory property.展开更多
Erythropoietin (EPO), a 34 kD glycopro-tein, is the principal growth factor regulating theproduction of circulating erythrocytes; EPO isessential for committed CFU - E erythroid pro-genitors to divide several times an...Erythropoietin (EPO), a 34 kD glycopro-tein, is the principal growth factor regulating theproduction of circulating erythrocytes; EPO isessential for committed CFU - E erythroid pro-genitors to divide several times and then to dif-ferentiate into erythrocytes. Like most receptorsfor hematopoietic growth factors, the erythro-poietin receptor (EPO - R) is a type I trans-membrane protein and a member of the cytokinereceptor superfamily. These receptors containfour conserved cysteines and a Trp - Ser - X -展开更多
BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in ...BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in patients with chronic HCV infection and investigate its possible association with anemia.METHODS: Ninety-three consecutive patients(62 males and 31 females) with chronic HCV infection, who had never received antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load measurement and genotype sequencing were also performed.RESULTS: Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia(19.4% vs 5.3%, P=0.040) compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia(70.0% vs 34.9%, P=0.030), lower EPO concentrations(median 16.35 vs 30.65 m U/m L, P=0.005), and higher HCV RNA viral load(median 891.5×103 vs 367.5×103 IU/m L, P=0.016). In multivariate regression analysis the presence of anti-EPO remained an independent predictor of anemia(adjusted OR: 14.303, 95% CI: 1.417-36.580, P=0.024). EPO response to anemia was less prominent among anti-EPO positive patients(P=0.001).CONCLUSIONS: Circulating anti-EPO are detected in a significant proportion of treatment-na?ve HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.展开更多
BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,th...BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.展开更多
BACKGROUND Hyporesponsiveness to erythropoiesis-stimulating agents(ESAs)is a prevalent problem in patients with chronic kidney disease.It is associated with increased morbidity and mortality in patients who undergo di...BACKGROUND Hyporesponsiveness to erythropoiesis-stimulating agents(ESAs)is a prevalent problem in patients with chronic kidney disease.It is associated with increased morbidity and mortality in patients who undergo dialysis.A significant proportion of patients do not respond to iron supplementation and conventional ESAs.We report a case of severe ESA hyporesponsiveness-related anemia that was successfully treated with oral roxadustat.CASE SUMMARY A 59-year-old Chinese woman had high blood glucose for 25 years,maintenance hemodialysis for 7 years,and recurrent dizziness and fatigue for more than 2 years.Laboratory tests showed severe anemia(hemoglobin level of 54 g/L),though bone marrow biopsy,fluorescence in situ hybridization,and hemolysis tests were within normal ranges.We initially administered first-line therapies and other adjuvant treatments,such as blood transfusions,ESAs,and adequate dialysis,but the patient did not respond as anticipated.Her erythropoietinresistant anemia was probably not only due to chronic renal insufficiency.The patient received the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat(100 mg,three times weekly).After 12 wk of treatment,the patient’s hemoglobin increased significantly,and her symptoms were alleviated.During the follow-up period,adverse drug reactions were controllable and tolerable.CONCLUSION Oral roxadustat is effective and tolerable for the treatment of ESA hyporesponsiveness-related anemia in patients undergoing hemodialysis.展开更多
AIM To assess safety and efficacy of early erythropoietin(Epo) administration in patients with out-of-hospital cardiac arrest(OHCA).METHODS A systematic literature search was performed using PubM ed,MEDLINE,EMBASE,EBS...AIM To assess safety and efficacy of early erythropoietin(Epo) administration in patients with out-of-hospital cardiac arrest(OHCA).METHODS A systematic literature search was performed using PubM ed,MEDLINE,EMBASE,EBSCO,CINAHL,Web of Science and Cochrane databases,of all studies published from the inception through October 10,2016.Inclusion criteria included:(1) Adult humans with OHCA and successful sustained return of spontaneous circulation;and(2) studies including mortality/brain death,acute thrombotic events as their end points.Primary efficacyoutcome was "brain death or Cerebral Performance Category(CPC) score of 5".Secondary outcomes were "CPC score 1,and 2-4","overall thrombotic events" and "acute coronary stent thrombosis".RESULTS We analyzed a total of 606 participants(n = 276 received Epo and n = 330 with standard of care alone) who experienced OHCA enrolled in 3 clinical trials.No significant difference was observed between the Epo and no Epo group in brain death or CPC score 5(OR = 0.77;95%CI:0.42-1.39),CPC score 1(OR = 1.16,95%CI:0.82-1.64),and CPC score 2-4(OR = 0.77,95%CI:0.44-1.36).Epo group was associated with increased thrombotic complications(OR = 2.41,95%CI:1.26-4.62) and acute coronary stent thrombosis(OR = 8.16,95%CI:1.39-47.99).No publication bias was observed.CONCLUSION Our study demonstrates no improvement in neurological outcomes and increased incidence of thrombotic events and acute coronary stent thrombosis in OHCA patients who were treated with Epo in addition to standard therapy.展开更多
AIM:To investigate the aqueous erythropoietin(EPO)levels and associated factors in patients with acute retinal vein occlusion(RVO).METHODS:The aqueous EPO level was measured in patients with macular edema(ME)secondary...AIM:To investigate the aqueous erythropoietin(EPO)levels and associated factors in patients with acute retinal vein occlusion(RVO).METHODS:The aqueous EPO level was measured in patients with macular edema(ME)secondary to acute branched retinal vein occlusion(BRVO)or central retinal vein occlusion(CRVO).Aqueous fluid from cataract patients served as the control.We also evaluated whether aqueous level of EPO was associated with factors such as serum EPO level,non-perfusion area,central macular thickness(CMT),and arterio-venous(AV)transit timeRESULTS:Twenty-seven RVO patients(16 BRVO,11CRVO)and 9 control subjects were enrolled in the study.The aqueous EPO level(mU/mL)was higher in RVO(68.2±54.3)than that in the control subjects(12.9±5.9).More specifically,the aqueous EPO level was higher in CRVO(118.9±52.1)than that in BRVO(33.3±10.8).However,no differences were found in serum EPO levels among three groups.CMT in RVO patients had a positive correlation with the aqueous EPO level(r=0.66).Also,in terms of non-perfusion area,the aqueous EPO levels were more elevated in the ischemic subgroup than in the non-ischemic subgroup in both BRVO and CRVO.CONCLUSION:Aqueous EPO levels are elevated in patients with macular edema secondary to recent onset RVO.Patients with CRVO have higher EPO levels than those with BRVO.The aqueous EPO level in RVO has a positive correlation with CMT and is associated with non-perfusion area.These results suggest that the aqueous EPO level could be associated with retinal ischemia and may be involved in the pathogenesis of macular edema secondary to RVO.展开更多
To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1800 g were ...To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1800 g were randomly assigned to treatment group 1 (n=15, receiving subcutaneous rhEpo 150 U/kg·time), treatment group 2 (n=15, receiving 250 U/kg·time), three times a week for 6 weeks, and control group (n=15, no treatment was given).All preterm infants received supplements of vitamin E (20 IU) and iron (20 mg) each day. Our results showed that postnatal decline of hemoglobin (Hb) and hematocrit (Hct) were lessened in the treatment groups, particularly in the group 2 and the differences were very significant (P【0.0001 for all). Treated infants had significantly higher reticulocyte counts (Ret) (P【0.0001 for all), but there was no significant difference between the two treatment groups (P】0.05).Serum iron dropped significantly in the treatment groups as compared with control group (P【0.01 for all),展开更多
BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1 α) and erythropoietin(EPO), possessing neuroprotective effect in the cerebral ischemia, might play an important role in the formation of cerebral ischemic tolerance...BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1 α) and erythropoietin(EPO), possessing neuroprotective effect in the cerebral ischemia, might play an important role in the formation of cerebral ischemic tolerance (IT). OBJECTIVE:To observe the neuroprotective effect of cerebral ischemic preconditioning(IPC) of rats, and the expression and mechanism of HIF-1α and target gene erythropoietin in the brain tissue following the formation of cerebral IT. DESIGN:A randomized and controlled observation. SETTING: Department of Neurology, the Affiliated Hospital of Medical College, Qingdao University. MATERIALS: Totally 84 enrolled adult healthy male Wistar rats of clean grade, weighing 250 to 300 g, were provided by the Animal Experimental Department, Tongji Medical College of Huazhong University of Science and Technology. Ready-to-use SABC reagent kit and rabbit anti-rat HIF-1α monoclonal antibody were purchased from Boshide Bioengineering Co.Ltd (Wuhan); Rabbit anti-rat EPO monoclonal antibody was purchased from Santa Cruz Company (USA). METHODS: This experiment was carried out in the Department of Anatomy, Medical College, Qingdao University during March 2005 to March 2006. ① The 84 rats were divided into 3 groups by a lot: IPC group (n=40), sham-operation group (n=40) and control group (n=4). In the IPC group, middle cerebral artery was occluded for 2 hours respectively on the 1st, 3rd, 7th, 14th and 21st days of the reperfusion following 10-minute preischemia was made using a modified middle cerebral artery second suture method from Zea-Longa. The rats were sacrificed 22 hours after reperfusion in the end of middle cerebral artery occlusion (MCAO). That was to say, after 10-minute preischemia, suture was exited to the external carotid artery and embedded subcutaneously. Middle cerebral artery was occluded again to form the second reperfusion at the set time point after reperfusion. Twenty-two hours later, rats were sacrificed; In the sham-operation group,the preischemia was substituted by sham-operation(only common carotid artery and crotch were exposed, and MCAO by suture was omitted), and the other procedures were the same as those in the IPC group. In the control group, rats were given sham-operation twice at an interval of one day, and they were sacrificed 24 hours after the second sham-operation. ② Brain tissue was taken from the rats in each group. Cerebral infarction area of each layer was measured with TTC staining, and total cerebral infarction volume (The total cerebral infarction area of each layer×interspace ) was calculated. After brain tissue was stained by haematoxylin-esoin (HE), the form of nerve cells was observed under an optical microscope, and the expressions of HIF-1αand EPO protein in the brain tissue were detected with immunohistochemical method. MAIN OUTCOME MEASURES: ①Cerebral infarction volume;②form of nerve cell; ③ the expression of HIF-1α and EPO protein in the brain tissue. RESULTS:Totally 84 rats were enrolled in the experiment. The dead rats were randomly supplied during the experiment, and finally 84 rats entered the stage of result analysis. ① Detection of cerebral infarction volume of rats in each group: Cerebral infarction volume in the IPC group was significantly smaller than that in the sham-operation group on the 1st, 3rd and 7th days after reperfusion respectively [(161.2±6.9) mm3 vs (219.9±11.2) mm3, (134.9±9.0) mm3 vs (218.6±13.0) mm3, (142.9±13.7) mm3 vs (221.3±14.2) mm3, t=8.924,10.587,7.947, P < 0.01]. ② Observation of nerve cell form of brain tissue: HE staining showed that the ischemic degree, range and cerebral edema degree of IPC group were significantly milder than those of sham-operation group. ③ The expressions of HIF-1α and EPO protein in cerebral cortex and hippocampus : The expression of HIF-1αof IPC group was significantly higher than that of sham-operation group on the 1st, 3rd and 7th days after reperfusion respectively (125.93±3.79 vs 117.65±5.60, 140.63±4.64 vs 119.33±4.26, 131.15±2.74 vs 107.60±3.89, t=2.449, 6.763,9.899,P < 0.05-0.01). The expression of EPO of IPC group was significantly higher than that of sham-operation group on the 3rd and 7th days after perfusion respectively (141.68±3.29 vs 126.33±4.51, 138.88±2.59 vs 125.58±6.18,t=5.499,3.970, P < 0.05). CONCLUSION: ① IPC can protect the never cells in rat brain and the best time to onset of cerebral IT induced by IPC is 1 to 7 days after reperfusion. ② Neuroprotective effect of cerebral IT might be related to the expression of HIF-1α and its target gene EPO.展开更多
BACKGROUND Hema-Plus,a recombinant human erythropoietin(rHuEPO)or epoetin alfa has shown effectiveness in correction of anemia in Thai population in clinical practice.This study was aimed to demonstrate efficacy and s...BACKGROUND Hema-Plus,a recombinant human erythropoietin(rHuEPO)or epoetin alfa has shown effectiveness in correction of anemia in Thai population in clinical practice.This study was aimed to demonstrate efficacy and safety under the evidencebased approach.AIM To evaluate the efficacy and safety of rHuEPO(Hema-Plus)for treatment of anemia over 12 wk in Thai patients with Stage V chronic kidney disease(CKD)on peritoneal dialysis(PD).METHODS This study was an open-label,multi-center study to enroll 30 CKD patients identified to start PD with hemoglobin(Hb)less than 9.5 g/dL,serum ferritin more than 100 ng/mL,serum transferrin saturation more than or equal to 20%and who had not previously received epoetin.Patients with conditions that could increase the risk of adverse effects from study participation or interfere with study outcomes,were using concomitant androgens or had secondary hyperparathyroidism were excluded.All eligible patients started Hema-Plus by SC injection at 4000 IU once or twice weekly(week 0)and with follow-up at weeks 2,4,8,and 12.Dosage adjustment could be done to achieve Hb level of 11-12 g/dL.Primary end point was mean change in Hb level from baseline to end of treatment(week 12).Safety was assessed throughout the study.Quality of life(QoL)was assessed using KDQOL-36.RESULTS All 30 enrolled patients completed the study.Mean(standard deviation)Hb at baseline(week 0)to the end of 12 wk was significantly increased from 7.39(1.29)g/dL to 11.15(1.73)g/dL(paired t-test,P value<0.001).Overall change of Hb means from baseline over the other 4 visits was statistically significantly increased(repeated measure ANOVA,P value<0.001).Ten out of 39 adverse events(AEs)were serious.Two serious AEs were probably related to study medication by investigators’assessment.At week 12,the QoL scores in all domains were significantly increased from baseline.CONCLUSION Hema-Plus administered for 12 wk for treatment of anemia in patients on PD effectively increased Hb levels with acceptable safety profile.展开更多
基金supported by the National Natural Science Foundation of China,No.81771355the Natural Science Foundation of Chongqing Science and Technology Bureau,Nos.CSTC2015jcyjA10096,cstc2021jcyj-msxmX0262(all to ZL)。
文摘Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.
基金supported by the National Natural Science Foundation of China,Nos.81871785 and 81672161(both to ZSY)。
文摘Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.
文摘BACKGROUND Methanol is a highly toxic,non-potable alcohol.Outbreaks of methanol toxicity occur due to its fraudulent addition to alcoholic beverages as a cheaper substitute for ethanol.Recently,alongside the coronavirus disease 2019(COVID-19)pandemic,rumors circulated on social media that consuming alcohol can prevent or cure the virus,leading to a COVID-19 and methanol-induced optic neuropathy(MON)syndemic.AIM To investigate the impact of erythropoietin(EPO)on the outcomes of patients diagnosed with MON.METHODS In this prospective study,105 patients presenting with acute bilateral visual loss secondary to methanol intoxication were enrolled from March to May 2020 at Farabi Eye Hospital.A comprehensive ocular examination was conducted for all participants.Recombinant human EPO and methylprednisolone were administered intravenously to all patients for three consecutive days.RESULTS The mean age of the participants was 39.9 years(±12.6).Ninety-four patients were male and eleven were female.The mean pre-treatment best corrected visual acuity(BCVA)improved from 2.0±0.86 to 1.39±0.69 logarithm of the minimum angle of resolution post-treatment(P<0.001),with significant improvement observed in all age categories and genders(P<0.001).Visual acuity improvement was also significant regardless of whether the patient presented before or after 72 h(P<0.001),and the post-treatment BCVA remained significant at all monthly follow-up visits(P<0.001).CONCLUSION EPO and methylprednisolone therapy have been shown to be effective in improving visual outcomes in patients with MON when administrated within the first month of exposure.Public awareness efforts are necessary to prevent further outbreaks of methanol toxicity in the current COVID-19 era.
文摘BACKGROUND Heart and kidney dysfunction frequently coexist in patients with acute heart failure due to the overlap between these two organ systems.Cardiorenal syndrome(CRS)results from pathology occurring in the heart and kidneys along with the consequences of dysfunction in one organ contributing to dysfunction in the other and vice versa.AIM To evaluate the use of erythropoietin(EPO)in patients with CRS and its effects on hemoglobin(Hb),major cardiovascular(CV)events,and hospitalization rates.METHODS On February 24,2022,searches were conducted using PubMed,MEDLINE,and EMBASE,and 148 articles were identified.A total of nine studies were considered in this systematic review.We assessed the included articles based on the National Heart,Lung,and Blood Institute quality assessment tools for controlled intervention and observational cohort or cross-sectional studies.An assessment of bias risk was conducted on the chosen studies,and data relevant to our review was extracted.RESULTS The systematic review of these studies concluded that most existing literature indicates that EPO improves baseline Hb levels and decreases myocardial remodeling and left ventricular dysfunction without reducing CV mortality.In addition,the effect of EPO on the hospitalization rate of patients with CRS needs to be further studied since this relationship is unknown.Future studies,such as randomized controlled clinical trials and prospective cohort studies,should be conducted to enhance the literature on the potential of EPO therapy in patients with CRS.CONCLUSION Our systematic review suggests that EPO therapy may have a significant role in managing CRS.The review highlights the potential benefits of EPO in improving baseline Hb levels,reducing the risk of major CV events,improving cardiac remodeling,myocardial function,New York Heart Association class,and B-type natriuretic peptide levels.However,the effect of EPO treatment on hospitalization remains unclear and needs further exploration.
文摘Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based biological markers for Blood-enriching Chinese herbs, we investigate the effect of 11 commonly used Blood-enriching herbs on erythropoietin (EPO) production in HepG2 cells. Herbs for nourishing Yin were tested for determining the specificity of Blood-enriching herbs in inducing EPO production. In addition, the effects of Blood-enriching herbs on nitric oxide (NO) production in both HepG2 cells and human umbilical vein endothelial cells (HUVECs) were also investigated. The results indicated that methanolic extracts of Blood-enriching herbs (but not Yin-nourishing herbs) showed characteristic pharmacological activity in inducing EPO production in HepG2 cells and NO release in HUVECs. The experimental findings, therefore, support the use of cell-based EPO production and NO release as biological markers for Blood-enriching Chinese tonifying herbs.
基金the National Natural Sciences Foundation of China(No.81500639)the Science Foundation of Hubei Society of Microcirculation(No.2019HX0020).
文摘The oxidative stress response plays an important role in the occurrence and development of diabetic kidney disease(DKD).It has become a new treatment target for DKD.In the current study,the effects of carbamylated erythropoietin(CEPO)on renal oxidative stress and damage in diabetic rats were examined.Thirty Sprague Dawley rats were intraperitoneally administered with 60 mg/kg streptozotocin to establish the diabetes model.The diabetic rats were randomly allocated into 4 groups(n=6 each):diabetes model group(DM group),DM+CEPO treatment group(DC group),DM+CEPO+EPO receptor(EPOR)blocking peptide treatment group(DCEB group),and DM+CEPO+CD131 blocking peptide treatment group(DCCB group).Meanwhile,a normal control group(NC group,n=6)was set up.Kidney tissues and blood samples were obtained for evaluation of oxidative stress and renal function.The results showed that diabetic rats exhibited increased oxidative stress in the kidney and early pathological changes associated with DKD.Treatment with CEPO reduced oxidative stress and attenuated renal dysfunction.However,diabetic rats treated with the combination of CEPO and EPOR blocking peptide or CD131 blocking peptide showed increased oxidative stress and reduced renal function when compared with CEPO treatment alone group.These results suggested that CEPO can protect against kidney damage in DKD by inhibiting oxidative stress injury via EPOR-CD131 heterodimers.
文摘Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progerdtor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were pos-让ive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors.
文摘Some in vitro experiments have shown that erythropoietin(EPO) increases resistance to apoptosis and facilitates neuronal survival following cerebral ischemia.However,results from in vivo studies are rarely reported.Perfusion-weighted imaging(PWI) and diffusion-weighted imaging(DWI) have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore,we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion.To validate this hypothesis,we established a rat model of focal cerebral ischemia/reperfusion injury,and treated with intra-cerebroventricular injection of EPO(5,000 U/kg) 20 minutes before injury.Brain tissue in the ischemic injury zone was sampled using MRI-guided localization.The relative area of abnormal tissue,changes in PWI and DWI in the ischemic injury zone,and the number of apoptotic cells based on Td T-mediated d UTP-biotin nick end-labeling(TUNEL) were assessed.Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI,increases cerebral blood volume,and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion.The experiment provides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.
基金Supported by (partly) A Research Grant from the Biomarker Society,Japan
文摘AIM:To investigate the protective effect of erythropoietin (Epo) against ischemia-reperfusion injury (IR/I) following the Pringle maneuver (PM),in comparison with conventional steroid administration in a prospective randomized trial. METHODS:Patients were randomized by age, sex, diagnosis, and surgical method, and assigned to three groups:(1) A steroid group (STRD, n= 9) who received 100 mg of hydrocortisone before PM, and on postoperative days 1, 2 and 3, followed by tapering until postoperative day 7; (2) An EPO1 group (n=10) who received 30 000 U of Epo before the PM and at the end of surgery; and (3) An EPO2 group (n=8) who received 60 000 U of Epo before the PM. Hemoglobin (Hb), hematocrit (Ht), aspartate aminotransferase (AST), alanine transaminase (ALT),lactate dehydrogenase (LDH), lactate, interleukin-6 (IL-6),and tumor necrosis factor(TNF)-α were measured before and just after (Day 0) surgery, and on postoperative days 1, 3, 7 and 14. RESULTS: There were no increases in Hb and Ht in the EPO1 and EPO2 groups. AST was signif icantly lower in EPO1 than in STRD on Day 0 (P=0.041), and lower in EPO1 than in STRD and EPO2 on Day 1 (P=0.018). ALT was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.020) and Day 1 (P=0.004). There were no signif icant inter-group differences in the levels of LDH and lactate. IL-6 was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.0036) and Day 1 (P=0.0451). TNF-α was signif icantly lower in EPO1 than in STRD and EPO2 on Day 0 (P=0.0006) and Day 1 (P<0.0001). Furthermore, hospitalization was signif icantly shorter in EPO1 and EPO2 than in STRD.CONCLUSION:Epo has greater potential than steroids to ameliorate IR/I after the PM. Epo at a dose of 30000 U, administered before PM and just after surgery, yields better results.
文摘BACKGROUND:During hepatectomy,a period of ischemia and restoration of the blood supply can result in hepatic ischemia-reperfusion injury(IRI).Current research indicates that erythropoietin(EPO)has a protective effect in animal models of cerebral ischemia,myocardial infarction,and renal IRI.However there is lack of research into the role of EPO in hepatic IRI.This study aimed to explore the role of EPO in hepatic IRI and its possible mechanism of action. METHODS:Thirty male Sprague-Dawley rats were divided into three groups:(1)ten rats in the experimental group were given 1000 IU/kg EPO one day before the operation;(2)ten rats in a control group were given normal saline preoperatively as a placebo;and(3)ten rats served as a sham-operated group.Hepatic IRI was induced by occluding the hepatic arteries of the three cephalad hepatic segments and the portal vein for about 45 minutes,while in the sham- operated group only laparotomy was performed.The levels of ALT and AST were tested 24 hours pre-and post-operation. All rats were sacrificed 24 hours after the operation to assess the pathologic changes in the liver and measure the expression of heme oxygenase-1(HO-1)through Western blotting and RT-PCR. RESULTS:Hepatic IRI was markedly mitigated in the experimental group as compared with the control group. Moreover,the expression of HO-1 at the level of both transcription and protein increased prominently(P<0.05) in the experimental group. CONCLUSION:These results demonstrate that EPO can up-regulate HO-1 in liver tissues and accordingly decrease hepatic injury through its anti-inflammatory property.
文摘Erythropoietin (EPO), a 34 kD glycopro-tein, is the principal growth factor regulating theproduction of circulating erythrocytes; EPO isessential for committed CFU - E erythroid pro-genitors to divide several times and then to dif-ferentiate into erythrocytes. Like most receptorsfor hematopoietic growth factors, the erythro-poietin receptor (EPO - R) is a type I trans-membrane protein and a member of the cytokinereceptor superfamily. These receptors containfour conserved cysteines and a Trp - Ser - X -
基金supported by a grant from the Special Account for Research Grants(ELKE)of the National and Kapodistrian University of Athens(No.70/3/7247)
文摘BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in patients with chronic HCV infection and investigate its possible association with anemia.METHODS: Ninety-three consecutive patients(62 males and 31 females) with chronic HCV infection, who had never received antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load measurement and genotype sequencing were also performed.RESULTS: Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia(19.4% vs 5.3%, P=0.040) compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia(70.0% vs 34.9%, P=0.030), lower EPO concentrations(median 16.35 vs 30.65 m U/m L, P=0.005), and higher HCV RNA viral load(median 891.5×103 vs 367.5×103 IU/m L, P=0.016). In multivariate regression analysis the presence of anti-EPO remained an independent predictor of anemia(adjusted OR: 14.303, 95% CI: 1.417-36.580, P=0.024). EPO response to anemia was less prominent among anti-EPO positive patients(P=0.001).CONCLUSIONS: Circulating anti-EPO are detected in a significant proportion of treatment-na?ve HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.
基金supported by a grant from the National Natural Science Foundation of China(81070122)
文摘BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.
基金Supported by the National Natural Science Foundation of China,No.81770730and the Hunan Provincial Natural Science Fund,No.2017JJ2352.
文摘BACKGROUND Hyporesponsiveness to erythropoiesis-stimulating agents(ESAs)is a prevalent problem in patients with chronic kidney disease.It is associated with increased morbidity and mortality in patients who undergo dialysis.A significant proportion of patients do not respond to iron supplementation and conventional ESAs.We report a case of severe ESA hyporesponsiveness-related anemia that was successfully treated with oral roxadustat.CASE SUMMARY A 59-year-old Chinese woman had high blood glucose for 25 years,maintenance hemodialysis for 7 years,and recurrent dizziness and fatigue for more than 2 years.Laboratory tests showed severe anemia(hemoglobin level of 54 g/L),though bone marrow biopsy,fluorescence in situ hybridization,and hemolysis tests were within normal ranges.We initially administered first-line therapies and other adjuvant treatments,such as blood transfusions,ESAs,and adequate dialysis,but the patient did not respond as anticipated.Her erythropoietinresistant anemia was probably not only due to chronic renal insufficiency.The patient received the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat(100 mg,three times weekly).After 12 wk of treatment,the patient’s hemoglobin increased significantly,and her symptoms were alleviated.During the follow-up period,adverse drug reactions were controllable and tolerable.CONCLUSION Oral roxadustat is effective and tolerable for the treatment of ESA hyporesponsiveness-related anemia in patients undergoing hemodialysis.
文摘AIM To assess safety and efficacy of early erythropoietin(Epo) administration in patients with out-of-hospital cardiac arrest(OHCA).METHODS A systematic literature search was performed using PubM ed,MEDLINE,EMBASE,EBSCO,CINAHL,Web of Science and Cochrane databases,of all studies published from the inception through October 10,2016.Inclusion criteria included:(1) Adult humans with OHCA and successful sustained return of spontaneous circulation;and(2) studies including mortality/brain death,acute thrombotic events as their end points.Primary efficacyoutcome was "brain death or Cerebral Performance Category(CPC) score of 5".Secondary outcomes were "CPC score 1,and 2-4","overall thrombotic events" and "acute coronary stent thrombosis".RESULTS We analyzed a total of 606 participants(n = 276 received Epo and n = 330 with standard of care alone) who experienced OHCA enrolled in 3 clinical trials.No significant difference was observed between the Epo and no Epo group in brain death or CPC score 5(OR = 0.77;95%CI:0.42-1.39),CPC score 1(OR = 1.16,95%CI:0.82-1.64),and CPC score 2-4(OR = 0.77,95%CI:0.44-1.36).Epo group was associated with increased thrombotic complications(OR = 2.41,95%CI:1.26-4.62) and acute coronary stent thrombosis(OR = 8.16,95%CI:1.39-47.99).No publication bias was observed.CONCLUSION Our study demonstrates no improvement in neurological outcomes and increased incidence of thrombotic events and acute coronary stent thrombosis in OHCA patients who were treated with Epo in addition to standard therapy.
文摘AIM:To investigate the aqueous erythropoietin(EPO)levels and associated factors in patients with acute retinal vein occlusion(RVO).METHODS:The aqueous EPO level was measured in patients with macular edema(ME)secondary to acute branched retinal vein occlusion(BRVO)or central retinal vein occlusion(CRVO).Aqueous fluid from cataract patients served as the control.We also evaluated whether aqueous level of EPO was associated with factors such as serum EPO level,non-perfusion area,central macular thickness(CMT),and arterio-venous(AV)transit timeRESULTS:Twenty-seven RVO patients(16 BRVO,11CRVO)and 9 control subjects were enrolled in the study.The aqueous EPO level(mU/mL)was higher in RVO(68.2±54.3)than that in the control subjects(12.9±5.9).More specifically,the aqueous EPO level was higher in CRVO(118.9±52.1)than that in BRVO(33.3±10.8).However,no differences were found in serum EPO levels among three groups.CMT in RVO patients had a positive correlation with the aqueous EPO level(r=0.66).Also,in terms of non-perfusion area,the aqueous EPO levels were more elevated in the ischemic subgroup than in the non-ischemic subgroup in both BRVO and CRVO.CONCLUSION:Aqueous EPO levels are elevated in patients with macular edema secondary to recent onset RVO.Patients with CRVO have higher EPO levels than those with BRVO.The aqueous EPO level in RVO has a positive correlation with CMT and is associated with non-perfusion area.These results suggest that the aqueous EPO level could be associated with retinal ischemia and may be involved in the pathogenesis of macular edema secondary to RVO.
文摘To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1800 g were randomly assigned to treatment group 1 (n=15, receiving subcutaneous rhEpo 150 U/kg·time), treatment group 2 (n=15, receiving 250 U/kg·time), three times a week for 6 weeks, and control group (n=15, no treatment was given).All preterm infants received supplements of vitamin E (20 IU) and iron (20 mg) each day. Our results showed that postnatal decline of hemoglobin (Hb) and hematocrit (Hct) were lessened in the treatment groups, particularly in the group 2 and the differences were very significant (P【0.0001 for all). Treated infants had significantly higher reticulocyte counts (Ret) (P【0.0001 for all), but there was no significant difference between the two treatment groups (P】0.05).Serum iron dropped significantly in the treatment groups as compared with control group (P【0.01 for all),
基金the Scientific andTechnological DevelopmentProgram of Qingdao City, No.No.05-1-NS-73
文摘BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1 α) and erythropoietin(EPO), possessing neuroprotective effect in the cerebral ischemia, might play an important role in the formation of cerebral ischemic tolerance (IT). OBJECTIVE:To observe the neuroprotective effect of cerebral ischemic preconditioning(IPC) of rats, and the expression and mechanism of HIF-1α and target gene erythropoietin in the brain tissue following the formation of cerebral IT. DESIGN:A randomized and controlled observation. SETTING: Department of Neurology, the Affiliated Hospital of Medical College, Qingdao University. MATERIALS: Totally 84 enrolled adult healthy male Wistar rats of clean grade, weighing 250 to 300 g, were provided by the Animal Experimental Department, Tongji Medical College of Huazhong University of Science and Technology. Ready-to-use SABC reagent kit and rabbit anti-rat HIF-1α monoclonal antibody were purchased from Boshide Bioengineering Co.Ltd (Wuhan); Rabbit anti-rat EPO monoclonal antibody was purchased from Santa Cruz Company (USA). METHODS: This experiment was carried out in the Department of Anatomy, Medical College, Qingdao University during March 2005 to March 2006. ① The 84 rats were divided into 3 groups by a lot: IPC group (n=40), sham-operation group (n=40) and control group (n=4). In the IPC group, middle cerebral artery was occluded for 2 hours respectively on the 1st, 3rd, 7th, 14th and 21st days of the reperfusion following 10-minute preischemia was made using a modified middle cerebral artery second suture method from Zea-Longa. The rats were sacrificed 22 hours after reperfusion in the end of middle cerebral artery occlusion (MCAO). That was to say, after 10-minute preischemia, suture was exited to the external carotid artery and embedded subcutaneously. Middle cerebral artery was occluded again to form the second reperfusion at the set time point after reperfusion. Twenty-two hours later, rats were sacrificed; In the sham-operation group,the preischemia was substituted by sham-operation(only common carotid artery and crotch were exposed, and MCAO by suture was omitted), and the other procedures were the same as those in the IPC group. In the control group, rats were given sham-operation twice at an interval of one day, and they were sacrificed 24 hours after the second sham-operation. ② Brain tissue was taken from the rats in each group. Cerebral infarction area of each layer was measured with TTC staining, and total cerebral infarction volume (The total cerebral infarction area of each layer×interspace ) was calculated. After brain tissue was stained by haematoxylin-esoin (HE), the form of nerve cells was observed under an optical microscope, and the expressions of HIF-1αand EPO protein in the brain tissue were detected with immunohistochemical method. MAIN OUTCOME MEASURES: ①Cerebral infarction volume;②form of nerve cell; ③ the expression of HIF-1α and EPO protein in the brain tissue. RESULTS:Totally 84 rats were enrolled in the experiment. The dead rats were randomly supplied during the experiment, and finally 84 rats entered the stage of result analysis. ① Detection of cerebral infarction volume of rats in each group: Cerebral infarction volume in the IPC group was significantly smaller than that in the sham-operation group on the 1st, 3rd and 7th days after reperfusion respectively [(161.2±6.9) mm3 vs (219.9±11.2) mm3, (134.9±9.0) mm3 vs (218.6±13.0) mm3, (142.9±13.7) mm3 vs (221.3±14.2) mm3, t=8.924,10.587,7.947, P < 0.01]. ② Observation of nerve cell form of brain tissue: HE staining showed that the ischemic degree, range and cerebral edema degree of IPC group were significantly milder than those of sham-operation group. ③ The expressions of HIF-1α and EPO protein in cerebral cortex and hippocampus : The expression of HIF-1αof IPC group was significantly higher than that of sham-operation group on the 1st, 3rd and 7th days after reperfusion respectively (125.93±3.79 vs 117.65±5.60, 140.63±4.64 vs 119.33±4.26, 131.15±2.74 vs 107.60±3.89, t=2.449, 6.763,9.899,P < 0.05-0.01). The expression of EPO of IPC group was significantly higher than that of sham-operation group on the 3rd and 7th days after perfusion respectively (141.68±3.29 vs 126.33±4.51, 138.88±2.59 vs 125.58±6.18,t=5.499,3.970, P < 0.05). CONCLUSION: ① IPC can protect the never cells in rat brain and the best time to onset of cerebral IT induced by IPC is 1 to 7 days after reperfusion. ② Neuroprotective effect of cerebral IT might be related to the expression of HIF-1α and its target gene EPO.
基金the Ethics Committee,Institute for the Development of Human Research Protections(IHRP),No.IHRP 2365/2556The Ethics Committee of Udon Thani Hospital,No.8/2559and Siriraj Institutional Review Board Faculty of Medicine Siriraj Hospital,Mahidol University,No.Si 588/2016.
文摘BACKGROUND Hema-Plus,a recombinant human erythropoietin(rHuEPO)or epoetin alfa has shown effectiveness in correction of anemia in Thai population in clinical practice.This study was aimed to demonstrate efficacy and safety under the evidencebased approach.AIM To evaluate the efficacy and safety of rHuEPO(Hema-Plus)for treatment of anemia over 12 wk in Thai patients with Stage V chronic kidney disease(CKD)on peritoneal dialysis(PD).METHODS This study was an open-label,multi-center study to enroll 30 CKD patients identified to start PD with hemoglobin(Hb)less than 9.5 g/dL,serum ferritin more than 100 ng/mL,serum transferrin saturation more than or equal to 20%and who had not previously received epoetin.Patients with conditions that could increase the risk of adverse effects from study participation or interfere with study outcomes,were using concomitant androgens or had secondary hyperparathyroidism were excluded.All eligible patients started Hema-Plus by SC injection at 4000 IU once or twice weekly(week 0)and with follow-up at weeks 2,4,8,and 12.Dosage adjustment could be done to achieve Hb level of 11-12 g/dL.Primary end point was mean change in Hb level from baseline to end of treatment(week 12).Safety was assessed throughout the study.Quality of life(QoL)was assessed using KDQOL-36.RESULTS All 30 enrolled patients completed the study.Mean(standard deviation)Hb at baseline(week 0)to the end of 12 wk was significantly increased from 7.39(1.29)g/dL to 11.15(1.73)g/dL(paired t-test,P value<0.001).Overall change of Hb means from baseline over the other 4 visits was statistically significantly increased(repeated measure ANOVA,P value<0.001).Ten out of 39 adverse events(AEs)were serious.Two serious AEs were probably related to study medication by investigators’assessment.At week 12,the QoL scores in all domains were significantly increased from baseline.CONCLUSION Hema-Plus administered for 12 wk for treatment of anemia in patients on PD effectively increased Hb levels with acceptable safety profile.
