Relaxin and Erythropoietin Significantly Reduce Uterine Tissue Damage during Experimental Ischemia–Reperfusion Injury

Successful uterus transplantation, a potential treatment method for women suffering from absolute uterine infertility, is negatively affected by ischemia–reperfusion injury (IRI). The aim of this study is to investigate the protective effect of relaxin (RLX) or/and erythropoietin (EPO) on experimental uterus IRI. Eighty rats, randomly assigned into eight groups (n = 10/group), were pretreated with either saline, 5 μg/kg human relaxin-2, 4000 IU/kg recombinant human erythropoietin or their combination. Ischemia was achieved by clamping the aorta and ovarian arteries for 60 min, following 120 min of reperfusion and tissue sampling. For sham animals, clamping was omitted during surgery. There were no differences in tissue histological score, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, myeloperoxidase (MPO) and TUNEL-positive cell count between all sham-operated rats. Pretreatment with RLX preserved normal tissue morphology, reduced MDA levels, MPO and TUNEL-positive cell count, preserved SOD activity and upregulated NICD and HES1 gene expression when compared to the control group. Pretreatment with EPO reduced MDA levels. In conclusion, pretreatment with RLX, EPO or a combination of both EPO and RLX significantly alleviates uterine tissue damage caused by IRI.     

Randomized Controlled Trial of Darbepoetin α Versus Continuous Erythropoietin Receptor Activator Injected Subcutaneously Once Every Four Weeks in Patients with Chronic Kidney Disease at the Pre-Dialysis Stage

Continuous erythropoietin receptor activator (CERA) seems to maintain a stable hemoglobin (Hb) level because its half-life is longer than darbepoetin α (DA). Twenty chronic kidney disease (CKD) patients at the pre-dialysis stage who had been administered DA for over 24 weeks were randomly assigned to receive subcutaneous CERA or DA once every four weeks during 48 weeks. In both groups, the rate of achievement of target Hb level changed from 70% to 100% in weeks 0 to 48, with no significant difference between the groups. Compared with week 0, the Hb level was significantly increased from week 24 in the DA group and from week 8 in the CERA group. In addition, the reticulocyte count was significantly increased from week 4 in the CERA group compared with the DA group. There was no significant difference in the levels of estimated glomerular filtration rate and iron status between both groups. Because of the small number of patients in this study, only limited conclusions can be drawn. However, the results suggest that subcutaneous administration of DA or CERA once every four weeks to predialysis patients has similar effects on achievement of target Hb levels.     

重组人红细胞生成素二聚体工程细胞的建立

目的建立重组人红细胞生成素二聚体工程细胞株。方法用重组人红细胞生成素二聚体表达载体转染COS-7细胞,通过dot blot进行检定。然后对CHO-dhfr-细胞进行稳定转染,再经过稀释克隆和MTX的加压扩增,筛选二聚体工程细胞株并进行传代及无血清培养基培养、目的蛋白纯化及检测。结果瞬时转染70h细胞有目的蛋白表达。稳定转染后选取表达量最高的细胞株为工程细胞株。该细胞株连续传15代及经无血清培养基培养,目的蛋白表达量均无明显下降。所表达的目的蛋白相对分子质量为70000,并具有高度特异性。结论已获得稳定高效表达重组人红细胞生成素二聚体的工程细胞株。     

重组人促红细胞生成素对感染性休克大鼠脑组织的保护作用

目的研究重组人促红细胞生成素（recombinant human erythropoietin,rhEPO）对感染性休克（septicshock,SS）大鼠脑组织的保护作用。方法将健康雄性Vistar大鼠36只按随机数字表法分为正常对照组（n=12）、感染性休克组（n=12）、rhEPO治疗组（n=12）,每组再分成2个时间点（61、2 h）,各时间点6只。感染性休克组和rhEPO治疗组以尾静脉注射内毒素（LPS）5 mg.kg-1制备感染性休克模型,rhEPO治疗组在出现休克症状时立刻腹腔注射rhEPO 5 000 U.kg-1;正常对照组大鼠给予等量生理盐水。术后各组各时间点大鼠分批腹腔麻醉后行眼球摘除术采血及断头取脑组织：取血清行NSE检测、脑组织匀浆行NO检测;提取右半侧脑组织海马区进行病理切片,行HE染色和TUNEL染色检查。结果与正常对照组比较,感染性休克组脑海马CA1区神经元损伤明显,可见大量TUNEL阳性细胞,NO、NSE含量显著升高（均P〈0.01）;rhEPO治疗组TUNEL阳性细胞和NO、NSE含量较感染性休克组明显降低（P〈0.01或P〈0.05）。结论 rhEPO可减轻感染性休克时脑组织损伤及海马区神经元细胞的凋亡,其机制可能与抑制NO的过量生成有关。     

The Association of Erythropoietin and Age-Related Macular Degeneration in Hemodialysis Patients: A Nationwide Population-Based Cohort Study

This population-based retrospective cohort study investigated the effectiveness of erythropoietin (EPO) treatment in reducing the risk of age-related macular degeneration (AMD) in hemodialysis patients, using the National Health Insurance Research Data of Taiwan. From the database, we identified 147,318 end-stage renal disease (ESRD) patients on hemodialysis who had been diagnosed in 2000–2014 to establish the propensity-score-matched EPO user cohort and non-EPO user cohort with equal sample size of 15,992. By the end of 2016, the cumulative incidence of AMD in EPO users was about 3.29% lower than that in non-EPO users (Kaplan–Meier survival p < 0.0001). The risk of AMD was 43% lower in EPO users than in non-EPO users, with an adjusted hazard ratio (aHR) of 0.57 (95% confidence interval (CI) = 0.51–0.64) estimated in the multivariate Cox model. A significant negative dose–response relationship was identified between the EPO dosage and the risk of AMD (p < 0.0001). Another beneficial effect of EPO treatment was a reduced risk of both exudative AMD (aHR = 0.48, 95% CI = 0.40–0.61) and non-exudative AMD (aHR = 0.61, 95% CI = 0.53–0.69), also in similar dose–response relationships (p < 0.0001). Our findings suggest that EPO treatment for hemodialysis patients could reduce AMD risk in a dose–response relationship.     

重组人促红素体内、体外生物学活性差异成因分析

目的分析造成重组人促红素(rHuEPO)体内、体外生物学活性差异的原因。方法按《中国药典》三部(2005版)方法检测rHuEPO样品体内、体外生物学活性,并通过等电聚焦电泳分析、唾液酸含量、纯度、N-糖链糖基化和相对分子质量检测,探讨样品体内、体外生物学活性产生差异的原因。结果体内、体外生物学活性有差异的rHuEPO样品中,存在糖链末端N-乙酰神经氨酸残基不完整的rHuEPO成分。纯度、N-糖链糖基化和相对分子质量检测结果未见异常。结论为提高rHuEPO产品质量,应在生产过程中有效去除N-乙酰神经氨酸残基不完整的rHuEPO。     

Evaluating Neuroprotective Effects of Uridine,Erythropoietin, and Therapeutic Hypothermia in a Ferret Model of Inflammation-Sensitized Hypoxic-Ischemic Encephalopathy

Perinatal hypoxic-ischemic (HI) brain injury, often in conjunction with an inflammatory insult, is the most common cause of death or disability in neonates. Therapeutic hypothermia (TH) is the standard of care for HI encephalopathy in term and near-term infants. However, TH may not always be available or efficacious, creating a need for novel or adjunctive neurotherapeutics. Using a near-term model of inflammation-sensitized HI brain injury in postnatal day (P) 17 ferrets, animals were randomized to either the control group (n = 43) or the HI-exposed groups: saline vehicle (Veh; n = 42), Ur (uridine monophosphate, n = 23), Epo (erythropoietin, n = 26), or TH (n = 24) to test their respective therapeutic effects. Motor development was assessed from P21 to P42 followed by analysis of cortical anatomy, ex vivo MRI, and neuropathology. HI animals took longer to complete the motor assessments compared to controls, which was exacerbated in the Ur group. Injury resulted in thinned white matter tracts and narrowed cortical sulci and gyri, which was mitigated in Epo-treated animals in addition to normalization of cortical neuropathology scores to control levels. TH and Epo treatment also resulted in region-specific improvements in diffusion parameters on ex vivo MRI; however, TH was not robustly neuroprotective in any behavioral or neuropathological outcome measures. Overall, Ur and TH did not provide meaningful neuroprotection after inflammation-sensitized HI brain injury in the ferret, and Ur appeared to worsen outcomes. By comparison, Epo appears to provide significant, though not complete, neuroprotection in this model.     

Preventing Brain Injury in the Preterm Infant—Current Controversies and Potential Therapies

Preterm birth is associated with a high risk of morbidity and mortality including brain damage and cerebral palsy. The development of brain injury in the preterm infant may be influenced by many factors including perinatal asphyxia, infection/inflammation, chronic hypoxia and exposure to treatments such as mechanical ventilation and corticosteroids. There are currently very limited treatment options available. In clinical trials, magnesium sulfate has been associated with a small, significant reduction in the risk of cerebral palsy and gross motor dysfunction in early childhood but no effect on the combined outcome of death or disability, and longer-term follow up to date has not shown improved neurological outcomes in school-age children. Recombinant erythropoietin has shown neuroprotective potential in preclinical studies but two large randomized trials, in extremely preterm infants, of treatment started within 24 or 48 h of birth showed no effect on the risk of severe neurodevelopmental impairment or death at 2 years of age. Preclinical studies have highlighted a number of promising neuroprotective treatments, such as therapeutic hypothermia, melatonin, human amnion epithelial cells, umbilical cord blood and vitamin D supplementation, which may be useful at reducing brain damage in preterm infants. Moreover, refinements of clinical care of preterm infants have the potential to influence later neurological outcomes, including the administration of antenatal and postnatal corticosteroids and more accurate identification and targeted treatment of seizures.