ABSTRACT
Renal transplantation is the optimal approach to improve the quality of life and restore normal life for patients with end-stage renal diseases.With the development of medical techniques and immunosuppressants, the shortterm survival of renal graft has been significantly prolonged, whereas the long-term survival remains to be urgently solved.Renal ischemia-reperfusion injury (IRI), acute rejection, chronic renal allograft dysfunction, renal fibrosis and other factors are still the major problems affecting the survival of renal graft.Relevant researches have always been hot spots in the field of renal transplantation.Meantime, 2020 is an extraordinary year.The novel coronavirus pneumonia (COVID-19) pandemic severely affects the development of all walks of life.Researches related to renal transplantation have also sprung up.In this article, the frontier hotspots of clinical and basic studies related to renal transplantation and the COVID-19 related researches in the field of renal transplantation in China were reviewed, aiming to provide novel therapeutic ideas and strategies.
ABSTRACT
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a common disease that occurs during the perinatal period. The primary cause of neonatal HIE is related to fetal intrauterine anoxia. Carbamylated erythropoietin (CEPO), a derivative of erythropoietin (EPO), does not exert any erythropoietic effect; however, the neuroprotective effects resemble those of EPO. Previous studies have shown the potential benefits of CEPO on the central nervous system. The present study aimed to investigate the role of CEPO in neuronal apoptosis during intrauterine HIE and the underlying mechanisms. RESULTS: To validate our hypothesis, we established an intrauterine HIE model by occluding the bilateral uteroovarian arteries of pregnant Sprague-Dawley rats. Compared to the I/R group, neuronal apoptosis in the CEPO group was significantly lower at 4, 12, 24, and 48 h (P < 0.05). CEPO significantly inhibited CC3 expression (P < 0.05) during the early-stages after ischemia-reperfusion (0.5, 4, 8, 12 and 24 h), upregulated Bcl-2 expression, and downregulated Bax expression at 4, 8, 12, and 24 h (P < 0.05). CONCLUSIONS: Carbamylated erythropoietin pretreatment inhibited the expression of proapoptotic protein CC3 in brain and regulated the Bcl-2/Bax ratio, resulting in reduced neuronal apoptosis and thus resulting in a protective effect on intrauterine HIE.
Subject(s)
Animals , Female , Pregnancy , Rats , Erythropoietin/analogs & derivatives , Apoptosis/drug effects , Neuroprotective Agents/therapeutic use , Hypoxia-Ischemia, Brain/prevention & control , Time Factors , Erythropoietin/therapeutic use , Rats, Sprague-Dawley , Hypoxia-Ischemia, Brain/pathology , Disease Models, AnimalABSTRACT
Objective To investigate any effects of carbamylated erythropoietin (CEPO) on the expression of LINGO-1,growth-associated protein-43 (GAP-43) and the infarcted volume after cerebral ischemia,so as to explore the effect of CEPO on neural regeneration after cerebral ischemia.Methods Forty-eight Sprague-Dawley rats were randomly divided into a sham operation group,an ischemia control group and a CEPO treatment group,each of 16.Middle cerebral artery occlusion (MCAO) was used to simulate focal cerebral ischemia in all except the rats in the sham operation group.Then the CEPO group was injected with 0.5 ml of CEPO,while the other two groups were given a 0.5 ml injection of normal saline daily for 7 days before they were sacrificed to prepare slices of brain tissue.Western blotting was used to detect the expression of LINGO-1 and activated caspase-3.Immunohistochemical staining was applied to observe the expression of GAP-43.The slices of brain tissue were stained with cresyl violet and the volume of infarction and edema were quantified with the Image J software.Results The average expression of LINGO1 in the sham operation group,the ischemia control group and the CEPO treatment group were (0.25±0.02),(1.22±0.06) and (0.66±0.05) respectively,with significant differences among the 3 groups.There was no expression of activated caspase-3 in the sham operation group.However,the expression of activated caspase-3 increased significantly (to 86.6±10.2)％ in the ischemia control group and increased significantly less (to 40.3±8.7)％ in the CEPO treatment group.The average positive expression of GAP-43 in the sham operation group,the ischemia control group and the CEPO treatment group were 0,(55.02± 1.62) and (72.11±3.23)/HP,respectively,with significant differences among them.Moreover,the average volumes of cerebral infarction and brain edema in the CEPO treatment group were significantly lower than those in the ischemia control group.Conclusions CEPO can inhibit the expression of LINGO-1 and activated caspase-3,promote the expression of GAP-43,reduce infarct volume and limit cerebral edema so as to promote neural regeneration after cerebral ischemia,at least in rats.
ABSTRACT
La producción de glóbulos rojos es controlada continuamente para suplir la desaparición de las células envejecidas y garantizar un aporte de oxígeno adecuado a todo el organismo. La citoquina pleitrópica eritropoyetina (Epo), originalmente definida por su rol en la eritropoyesis para prevenir la muerte programada de progenitores eritroides en la médula ósea, ha demostrado un rol antiapoptótico protector sobre diversos tejidos no hematopoyéticos. A la reconocida eficacia del tratamiento con eritropoyetina recombinante humana (rhuEpo) para contrarrestar la anemia que acompaña a patologías muy diversas, se agregan algunos aspectos que impiden lograr los resultados terapéuticos esperados, ya sea por resistencia al tratamiento o por el desarrollo de efectos adversos. Con el fin de prevenir estos efectos, así como reducir las dosis de rhuEpo en tratamientos crónicos se han desarrollado nuevos agentes que presentan modificaciones estructurales de la Epo, o bien alteraciones en las propiedades/actividad de la Epo nativa. Dado que, actualmente, los resultados sobre los efectos de la Epo sobre morbilidad/ mortalidad en diversas patologías no están suficientemente claros, nuevas investigaciones serán útiles para resolver dudas sobre la efectividad de la eritropoyetina y sus derivados o agentes alternativos con el fin de proveer bases sólidas para el desarrollo de ensayos clínicos concluyentes.
Erythropoietin (Epo), the cytokine required for promoting erythropoiesis through the proliferation and differentiation of erythroid cells, has been reported to act as a pleiotropic cytokine beyond the hematopoietic system. In contrast with the potentially beneficial effects attributed to recombinant human erythropoietin (rhuEpo), research has advanced to indicate that mortality and morbidity rates are increased in some patient groups when treated with rhuEpo. Some cardiac and systemic conditions may predispose to adverse events, and other factors, such as proinflammatory agents, may lead to resistance to erythropoietin treatment. Many compounds are currently under investigation in order to avoid these unwanted effects and to reduce the rhuEpo dose during chronic therapies. They are either erythropoiesis-stimulating agents different from erythropoietin or structurally modified erythropoietins with altered properties and activities. In recent reports, contrasting data have raised several concerns regarding the effectiveness of erythropoietin treatment to prevent adverse events. Therefore, much investigation is needed to provide a solid basis for the development of conclusive clinical trials.
A produção de glóbulos vermelhos é controlada continuamente para suprir o desaparecimento das células envelhecidas e garantir uma contribuição de oxigênio adequado a todo o organismo. A citocina pleiotrópica eritropoietina (Epo), originalmente definida por seu papel na eritropoiese para prevenir a morte programada de progenitores eritroides na medula óssea, tem demonstrado um papel anti-apoptótico protetor sobre diversos tecidos não hematopoiéticos. Adicionam-se à reconhecida eficácia do tratamento com eritropoietina recombinante humana (rhuEpo), para contra-arrestar a anemia que acompanha patologias muito diversas, alguns aspectos que impedem alcançar os resultados terapêuticos esperados, quer seja por resistência ao tratamento ou pelo desenvolvimento de efeitos adversos. Com o fim de prevenir estes efeitos, bem como reduzir as doses de rhuEpo em tratamentos crônicos foram desenvolvidos novos agentes que apresentam modificações estruturais da Epo, ou então alterações nas propriedades/atividade da Epo nativa. Devido a que, atualmente, os resultados sobre os efeitos da Epo sobre morbidade/mortalidade em diversas patologias não estão suficientemente claros, novas pesquisas serão úteis para resolver dúvidas sobre a efetividade da eritropoietina e seus derivados ou agentes alternativos visando a fornecer bases sólidas para o desenvolvimento de ensaios clínicos concludentes.
Subject(s)
Humans , Erythropoiesis , Erythropoietin/adverse effects , Erythropoietin/therapeutic use , Signal Transduction , Biological Factors , Erythropoietin/chemistry , Receptors, Erythropoietin/therapeutic useABSTRACT
OBJECTIVE:To study the effects of carbamylated erythropoietin(CEPO)on cardiovascular microcirculation in rats with diabetes mellitus. METHODS:Rats were randomly divided into blank control group,model group,CEPO low-dose,medi-um-dose and high-dose groups(500,1 000,2 000 u/kg)with 12 in each group. The rats in the last 4 groups were reduced diabetes mellitus model. All rats were given relevant medicine intragastrically twice a week,coronary microcirculation endothelial cells were separated after consecutive 4 weeks. Enzyme-linked immunosorbent assay was conducted to detect levels of peripheral serum prosta-cyclin (PGI2),vasoconstrictor endothelin-1 (ET-1),angiotensin Ⅱ(AngⅡ) and von Willebrand factor (vWF) of rats in each group;in vitro CCK 8 test was used to detect endothelial cell activity(OD value);real-time quantitative polymerase chain reaction was adopted to detect proliferation-related genes(Ki67,p16),poptosis-related genes(Bad,Bax),and expressions of protein vas-cular endothelial growth factor(VEGF)and AngⅠ. RESULTS:Compared with blank control group,levels of PGI2,ET-1,AngⅡand vWF in serum in model group increased;OD value deceased;Ki67,p16,Bax and VEGF expression decreased;the difference was statistically significant (P0.05). CONCLUSIONS:CEPO maybe improve the coronary microcirculation function by upregulating VEGF expression in coro-nary microcirculation endothelial cells and promoting endothelial cells’regeneration.
ABSTRACT
A previous animal study has shown the effects of erythropoietin (EPO) and its non-erythropoietic carbamylated derivative (CEPO) on neurogenesis in the dentate gyrus. In the present study, we sought to investigate the effect of EPO on adult hippocampal neurogenesis, and to compare the ability of EPO and CEPO promoting dendrite elongation in cultured hippocampal neural progenitor cells. Two-month-old male BALB/c mice were given daily injections of EPO (5 U/g) for seven days and were sacrificed 12 hours after the final injection. Proliferation assays demonstrated that EPO treatment increased the density of bromodeoxyuridine (BrdU)-labeled cells in the subgranular zone (SGZ) compared to that in vehicle-treated controls. Functional differentiation studies using dissociated hippocampal cultures revealed that EPO treatment also increased the number of double-labeled BrdU/microtubule-associated protein 2 (MAP2) neurons compared to those in vehicle-treated controls. Both EPO and CEPO treatment significantly increased the length of neurites and spine density in MAP2(+) cells. In summary, these results provide evidences that EPO and CEPO promote adult hippocampal neurogenesis and neuronal differentiation. These suggest that EPO and CEPO could be a good candidate for treating neuropsychiatric disorders such as depression and anxiety associated with neuronal atrophy and reduced hippocampal neurogenesis.