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
The erythropoietin receptor （EPOR） has shown to play an important role in fetal survival by promoting the maturation of red blood cells in many studies of uterine capacity and litter size in swine. In this study, we...The erythropoietin receptor （EPOR） has shown to play an important role in fetal survival by promoting the maturation of red blood cells in many studies of uterine capacity and litter size in swine. In this study, we screened the porcine EPOR gene for mutations and identified five single nucleotide polymorphisms （SNPs）： g.705G〉T in intron 1, g.2 373C〉T in intron 4, and g.2 882C〉T, g.3 035A〉G, and g.3 132A〉T in intron 6. We then genotyped 247 Beijing Black （BB） sows and compared the polymorphism data with the litter sizes of 1 375 parities among the sows. At first parity, there was no association of g.2 882C〉T and g.3 132A〉T with litter sizes. However, the CT sows in g.2 882C〉T had 2.13 higher total number born （TNB） （P〈0.01） and 1.81 higher number born alive （NBA） （P〈0.01） than the CC sows and the heterozygous sows in g.3 132A〉T had the highest litter size when compared to the two homozygotes for the later parities （P〈0.05）. In the g.3 035A〉G SNP, for the later parities, the TNB of the sows with the GG genotype was 3.81 higher （P〈0.01） and the NBA was 2.75 higher （P〈0.01） than that with the AA genotype but no difference at first parity. The G allele of the EPOR g.705G〉T SNP was associated with a greater litter size at both the first parity （P〈0.05） and later parities （P〈0.01）. Furthermore, we determined the allele frequencies for this SNP among five Chinese indigenous pig breeds （Erhualian, Laiwu Black, Meishan, Min, and Rongchang） and three western commercial pig breeds （Duroc, Landrace, and Large White）. The G allele of the EPOR g.705G〉T SNP was significantly more common in the more prolific Chinese breeds. These results indicated that the EPOR could be an important candidate gene for litter size and g.705G〉T can serve as a useful genetic marker for improving litter size in both first and later parities in swine.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
以EPO抗体修饰的Fe_(3)O_(4)粉末-聚丙烯酰胺凝胶为结合相,明胶凝胶为扩散层,通过薄膜扩散梯度技术(DGT)与紫外光谱法,对去离子水、人体尿液中的rhEPO进行富集和检测的实验研究。在25℃、常压环境下,DGT中结合相的饱和富集容量为0.0758...以EPO抗体修饰的Fe_(3)O_(4)粉末-聚丙烯酰胺凝胶为结合相,明胶凝胶为扩散层,通过薄膜扩散梯度技术(DGT)与紫外光谱法,对去离子水、人体尿液中的rhEPO进行富集和检测的实验研究。在25℃、常压环境下,DGT中结合相的饱和富集容量为0.0758μg cm^(2),当pH值为5.5~8.0、无机盐浓度为0.3%~1.5%时,rhEPO的检测回收率基本不受影响。对质量浓度为6~15 ng mL的rhEPO水溶液进行检测时,rhEPO检测回收率的平均值为81.9%;对质量浓度为5~20 ng mL的rhEPO人体尿液进行检测时,rhEPO检测回收率的平均值为79.8%。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
Two different immunoassay methods, competitive indirect enzyme-linked immuno-sorbent assay (CI-ELISA) and amplificative competitive indirect ELISA (ACI-ELISA) using biotin-avidin complex system were studied to detect ...Two different immunoassay methods, competitive indirect enzyme-linked immuno-sorbent assay (CI-ELISA) and amplificative competitive indirect ELISA (ACI-ELISA) using biotin-avidin complex system were studied to detect rhEPO. The linear ranges were 50-20000 ng/mL and 10-50000 ng/mL for CI-ELISA and ACI-ELISA, respectively. The low detection limits of CI-ELISA and ACI-ELISA were 62.8 ng/mL and 8.5 ng/mL, respectively.展开更多
We describe a two-step method that uses wheat germ agglutinin immobilized on Sepharose gel followed by immunoaffinity chromatography (IAC) to extract recombinant human erythropoietin and Darbepoetin from equine plasma...We describe a two-step method that uses wheat germ agglutinin immobilized on Sepharose gel followed by immunoaffinity chromatography (IAC) to extract recombinant human erythropoietin and Darbepoetin from equine plasma. Lectin affinity chromatography was shown to be an effective approach for isolating these epoetins from plasma and in combination with IAC;this method gave superior recovery when compared to the use of the latter technique alone. Moreover, due to the ease with which it can be scaled up, it is particularly well suited for pre-concentrating larger volumes of samples prior to IAC and this provides a facile way of improving the overall sensitivity with which these foreign proteins can be detected in equine plasma.展开更多
Objective: To assess perceptions about ease of use and other benefits of Wepox PenTM (loaded with 30,000 IU cartridge of recombinant erythropoietin) in the management of anemia in adult chronic kidney disease (CKD) pa...Objective: To assess perceptions about ease of use and other benefits of Wepox PenTM (loaded with 30,000 IU cartridge of recombinant erythropoietin) in the management of anemia in adult chronic kidney disease (CKD) patients. Material and methods: In this prospective, observational, multicentric post marketing surveillance, adult CKD patients treated with erythropoietin were enrolled from November 2015 to December 2016 to understand their opinions about Wepox PenTM. Ease of use of pen, ease of administering accurate dose, confidence in administration and ease of storage and disposal of cartridge were assessed on five points Likert scale: 1. very easy;2. somewhat easy;3. neither easy nor difficult;4. somewhat difficult;5. very difficult. Global assessment was performed on five points scale: 1. excellent;2. very good;3. good;4. average;5. not good. Safety was recorded by checking pain and discomfort and adverse events. Results: A total of 263 patients (mean age 32.87 years;66% male;34% female) were enrolled. Number of patients reporting ease of use as “very easy” from 209 (80.7%) at baseline increased to 245 (94.6%) and 249 (96.1%) at visit 2 (p = 0.001) and visit 3 (p = 0.001) respectively. Number of “very easy” response for accurate dose increased from 236 (91.1%) at visit 1 to 246 (95%) at visit 2 (p = 0.84) and 249 (96.1%) at visit 3 (p = 0.001). Number of the patients with “no pain” at injection site increased from 177 (68.3%) at visit 1 to 205 (79.2%) and 212 (81.9%) at visit 2 (p = 0.001) and visit 3 (p = 0.001) respectively. Improvement in number of patients with “no hurt” at visit 2 (p = 0.538) and visit 3 (p = 0.286) was not statistically significant. Number of patients reporting “somewhat easy” to “very easy” confidence in self injection increased from 251 (96.9%) at visit 2 to 255 (98.5%) at visit 3. Number of patients reporting ease of storage and disposal of cartridge as “somewhat easy” to “very easy” increased from 254 (98.1%) at visit 2 to 256 (98.9%) at visit 3. According to the global assessment, 144 (56.3%) cases reported “excellent” response. “Very good” and “Good” responses were reported by 106 (41.4%) and 6 (2.3%) patients respectively. A total of 230 (98.7%) patients said that they would prefer to use erythropoietin pen device for further treatment too. Conclusion: Wepox PenTM(recombinant erythropoietin) is easy to use and does not cause significant pain or discomfort. Ability to self-administer recombinant erythropoietin with Wepox PenTM is a great advantage which can make a significant difference for both CKD patients and doctors. Storage and disposal of cartridge is also easy.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
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 grants from the National High Technology R&D Program of China (200810Z133)the National Key Technology R&D Program of China (2006BAD01A08)the Fundamental Research of Chinese Academy of Agricultural Sciences (2009qn-5)
文摘The erythropoietin receptor （EPOR） has shown to play an important role in fetal survival by promoting the maturation of red blood cells in many studies of uterine capacity and litter size in swine. In this study, we screened the porcine EPOR gene for mutations and identified five single nucleotide polymorphisms （SNPs）： g.705G〉T in intron 1, g.2 373C〉T in intron 4, and g.2 882C〉T, g.3 035A〉G, and g.3 132A〉T in intron 6. We then genotyped 247 Beijing Black （BB） sows and compared the polymorphism data with the litter sizes of 1 375 parities among the sows. At first parity, there was no association of g.2 882C〉T and g.3 132A〉T with litter sizes. However, the CT sows in g.2 882C〉T had 2.13 higher total number born （TNB） （P〈0.01） and 1.81 higher number born alive （NBA） （P〈0.01） than the CC sows and the heterozygous sows in g.3 132A〉T had the highest litter size when compared to the two homozygotes for the later parities （P〈0.05）. In the g.3 035A〉G SNP, for the later parities, the TNB of the sows with the GG genotype was 3.81 higher （P〈0.01） and the NBA was 2.75 higher （P〈0.01） than that with the AA genotype but no difference at first parity. The G allele of the EPOR g.705G〉T SNP was associated with a greater litter size at both the first parity （P〈0.05） and later parities （P〈0.01）. Furthermore, we determined the allele frequencies for this SNP among five Chinese indigenous pig breeds （Erhualian, Laiwu Black, Meishan, Min, and Rongchang） and three western commercial pig breeds （Duroc, Landrace, and Large White）. The G allele of the EPOR g.705G〉T SNP was significantly more common in the more prolific Chinese breeds. These results indicated that the EPOR could be an important candidate gene for litter size and g.705G〉T can serve as a useful genetic marker for improving litter size in both first and later parities in swine.
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.
文摘以EPO抗体修饰的Fe_(3)O_(4)粉末-聚丙烯酰胺凝胶为结合相,明胶凝胶为扩散层,通过薄膜扩散梯度技术(DGT)与紫外光谱法,对去离子水、人体尿液中的rhEPO进行富集和检测的实验研究。在25℃、常压环境下,DGT中结合相的饱和富集容量为0.0758μg cm^(2),当pH值为5.5~8.0、无机盐浓度为0.3%~1.5%时,rhEPO的检测回收率基本不受影响。对质量浓度为6~15 ng mL的rhEPO水溶液进行检测时,rhEPO检测回收率的平均值为81.9%;对质量浓度为5~20 ng mL的rhEPO人体尿液进行检测时,rhEPO检测回收率的平均值为79.8%。
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Two different immunoassay methods, competitive indirect enzyme-linked immuno-sorbent assay (CI-ELISA) and amplificative competitive indirect ELISA (ACI-ELISA) using biotin-avidin complex system were studied to detect rhEPO. The linear ranges were 50-20000 ng/mL and 10-50000 ng/mL for CI-ELISA and ACI-ELISA, respectively. The low detection limits of CI-ELISA and ACI-ELISA were 62.8 ng/mL and 8.5 ng/mL, respectively.
文摘We describe a two-step method that uses wheat germ agglutinin immobilized on Sepharose gel followed by immunoaffinity chromatography (IAC) to extract recombinant human erythropoietin and Darbepoetin from equine plasma. Lectin affinity chromatography was shown to be an effective approach for isolating these epoetins from plasma and in combination with IAC;this method gave superior recovery when compared to the use of the latter technique alone. Moreover, due to the ease with which it can be scaled up, it is particularly well suited for pre-concentrating larger volumes of samples prior to IAC and this provides a facile way of improving the overall sensitivity with which these foreign proteins can be detected in equine plasma.
文摘Objective: To assess perceptions about ease of use and other benefits of Wepox PenTM (loaded with 30,000 IU cartridge of recombinant erythropoietin) in the management of anemia in adult chronic kidney disease (CKD) patients. Material and methods: In this prospective, observational, multicentric post marketing surveillance, adult CKD patients treated with erythropoietin were enrolled from November 2015 to December 2016 to understand their opinions about Wepox PenTM. Ease of use of pen, ease of administering accurate dose, confidence in administration and ease of storage and disposal of cartridge were assessed on five points Likert scale: 1. very easy;2. somewhat easy;3. neither easy nor difficult;4. somewhat difficult;5. very difficult. Global assessment was performed on five points scale: 1. excellent;2. very good;3. good;4. average;5. not good. Safety was recorded by checking pain and discomfort and adverse events. Results: A total of 263 patients (mean age 32.87 years;66% male;34% female) were enrolled. Number of patients reporting ease of use as “very easy” from 209 (80.7%) at baseline increased to 245 (94.6%) and 249 (96.1%) at visit 2 (p = 0.001) and visit 3 (p = 0.001) respectively. Number of “very easy” response for accurate dose increased from 236 (91.1%) at visit 1 to 246 (95%) at visit 2 (p = 0.84) and 249 (96.1%) at visit 3 (p = 0.001). Number of the patients with “no pain” at injection site increased from 177 (68.3%) at visit 1 to 205 (79.2%) and 212 (81.9%) at visit 2 (p = 0.001) and visit 3 (p = 0.001) respectively. Improvement in number of patients with “no hurt” at visit 2 (p = 0.538) and visit 3 (p = 0.286) was not statistically significant. Number of patients reporting “somewhat easy” to “very easy” confidence in self injection increased from 251 (96.9%) at visit 2 to 255 (98.5%) at visit 3. Number of patients reporting ease of storage and disposal of cartridge as “somewhat easy” to “very easy” increased from 254 (98.1%) at visit 2 to 256 (98.9%) at visit 3. According to the global assessment, 144 (56.3%) cases reported “excellent” response. “Very good” and “Good” responses were reported by 106 (41.4%) and 6 (2.3%) patients respectively. A total of 230 (98.7%) patients said that they would prefer to use erythropoietin pen device for further treatment too. Conclusion: Wepox PenTM(recombinant erythropoietin) is easy to use and does not cause significant pain or discomfort. Ability to self-administer recombinant erythropoietin with Wepox PenTM is a great advantage which can make a significant difference for both CKD patients and doctors. Storage and disposal of cartridge is also easy.
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.
