UNASSIGNED: Recent studies have reported that helix B surface polypeptide (HBSP), an erythropoietin derivative, exhibits strong tissue protective effects, independent of erythropoietic effects, in a renal ischemia-reperfusion (IR) injury model. Meanwhile, the transforming growth factor-β (TGF-β) superfamily member glial cell line-derived neurotrophic factor (GDNF) demonstrated protective effect on podocytes in vitro. Using a rat puromycin aminonucleoside nephropathy (PAN) model, this study observed the renal protective effect of HBSP and investigated its renal protective effect on podocytes and mechanism related to GDNF.
UNASSIGNED: Rats nephropathy model was induced by injection of 60 mg/kg of PAN via the tail vein. Rats in the PAN + HBSP group were injected intraperitoneally with HBSP (8 nmol/kg) 4 h before the model was induced, followed by intraperitoneal injections of HBSP once every 24 h for 7 consecutive days. The 24-hour urinary protein level was measured once every other day, and blood and renal tissue samples were collected on the 7th day for the examination of renal function, complete blood count, renal pathological changes and the expression levels of GDNF.
UNASSIGNED: Compared with the control group, the PAN nephropathy rat model showed a large amount of urinary protein. The pathological manifestations were mainly extensive fusion and disappearance of foot processes, along with vacuolar degeneration of podocytes and their separation from the glomerular basement membrane. GDNF expression was upregulated. Compared with the PAN + vehicle group, the PAN + HBSP group showed decreased urinary protein (p < 0.05). Pathological examination revealed ameliorated glomerular injury and vacuolar degeneration of podocytes. The expression of GDNF in the PAN nephropathy group was increased, when compared with the control group. The greatest expression of GDNF observed in the PAN + HBSP group (p < 0.05).
UNASSIGNED: The expression of GDNF in the kidney of PAN rat model was increased. HBSP reduced urinary protein, ameliorated pathological changes in renal podocytes, increased the expression of GDNF in the PAN rat model. HBSP is likely to exert its protective effects on podocytes through upregulation of GDNF expression.

The clinical treatment of bone defects includes allogeneic bone transplantation and autologous bone transplantation. However, they all have their own limitations, and the scope of application is limited. In recent years, bone tissue engineering scaffolds based on a variety of materials have been well developed and achieved good bone regeneration ability. However, most scaffold materials always face problems such as high biotoxicity, leading to inflammation and poor bioactivity, which limits the bone regeneration effect and prolongs the bone regeneration time. In our work, we prepared hydroxyapatite, erythropoietin (EPO), and osteogenic growth peptide (OGP) codoped type-I collagen (Col I) polypeptide nanofiber membranes (NFMs) by electrostatic spinning. In cell experiments, the composite NFMs had low cytotoxicity and promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. Quantitative real-time polymerase chain reaction and alkaline phosphatase staining confirmed the high expression of osteogenic genes, and alizarin red S staining directly confirmed the appearance of calcium nodules. In animal experiments, the loaded hydroxyapatite formed multiple independent mineralization centers in the defect center. Under the promotion of Col I, EPO, and OGP, the bone continued to grow along the mineralization centers as well as inward the defect edge, and the bone defect completely regenerated in about two months. The hematological and histological analyses proved the safety of the experiments. This kind of design to promote bone regeneration by simulating bone composition, introducing mineralization center and signal molecules, can shorten repair time, improve repair effect, and has good practical prospects in the future.

OBJECTIVE: Our study aimed to investigate the relationship between vascular endothelial growth factor (VEGF), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory complex, erythropoietin (EPO) levels, and ocular hemodynamics in patients diagnosed with primary open-angle glaucoma (POAG).
METHODS: This is a prospective observational study. Patients diagnosed with POAG at The Sixth Hospital of Wuhan hospital between November 2022 and February 2023were enrolled.The patients were categorized into three groups based on the average visual field defect (mean deviation, MD) value: severe injury group (MD > 12 dB, 93 cases), moderate injury group (7 ≤ MD ≤ 12 dB, 89 cases), and mild injury group (MD < 7 dB, 85 cases). The levels of VEGF, NLRP3 inflammatory complex, EPO, and ocular hemodynamics were compared among the groups. Furthermore, the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG was analyzed using Pearson correlation analysis. After adjusting for confounding factors such as age and gender, multivariate Logistic regression analysis was performed with the ocular hemodynamics indexes being used as dependent variables, and VEGF, NLRP3, ASC, Caspase-1, and EPO being used as independent variables.
RESULTS: A total of267 patients with POAG were enrolled. There were no significant differences in sex, age, body mass index, systolic blood pressure, diastolic blood pressure, smoking, alcohol consumption, and blood glucose between the two groups (P > 0.05). The levels of NLRP3, ASC, Caspase-1, and EPO in the severe and moderate injury groups were higher than those in the mild injury group, whereas the VEGF levels were lower in the severe and moderate groups compared to the mild group, showing significant differences (P < 0.05). The severe group exhibited higher levels of NLRP3, ASC, Caspase-1, and EPO than the moderate group, while the VEGF levels were lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). The peak systolic velocity(PSV) and resistance index (RI) were higher in the severe and moderate groups than in the mild group, whereas the EDV was significantly lower in the severe and moderate groups compared to the mild group (P < 0.05). The severe group exhibited higher PSV and RI values compared to the moderate group, while the EDV was lower in the severe group compared to the moderate group, showing significant differences (P < 0.05). Pearson correlation analysis was performed to examine the relationship between VEGF, NLRP3, EPO levels, and ocular hemodynamics in patients with POAG. VEGF, NLRP3, ASC, Caspase-1, and EPO showed positive correlations with PSV and RI, and negative correlations with EDV in patients with POAG. Regression analysis showed that VEGF, NLRP3, ASC, Caspase-1 and EPO were significantly correlated with ocular hemodynamics in POAG (all P < 0.001).
CONCLUSIONS: We demonstrated that the levels of VEGF, NLRP3 inflammatory complex, and EPO were highly associated with ocular hemodynamics in patients diagnosed with POAG.

OBJECTIVE: This first-in-human trial aimed to investigate the pharmacokinetics and pharmacodynamics characteristics and safety and tolerability of single ascending doses of subcutaneous polyethylene glycol-erythropoietin (PEG-EPO) in healthy subjects.
METHODS: In this phase I, randomized, double-blind, placebo-controlled, dose-escalating trial, subjects were sequentially enrolled into 7 cohorts with 12 subjects in each cohort and randomized in a 5:1 ratio to receive a single dose of 0.2, 0.4, 0.8, 1.6, 2.4, 3.6, or 4.8 µg/kg PEG-EPO or matching placebo. Safety and tolerability including dose-limiting toxicities (DLTs) were assessed. Pharmacokinetics parameters, including Cmax, AUC0-inf, Tmax, and t1/2, and pharmacodynamics parameters, including reticulocyte count and hemoglobin content, were evaluated.
RESULTS: Eighty-four subjects (median age 30.4 years and 77.4% male) were enrolled. No subjects developed DLTs. Any grade treatment-related adverse events occurred in 66.7% of the subjects, but most (92.9%) were mild. No serious adverse events and no death occurred. Forty percent of the subjects receiving PEG-EPO had iron decreased, 27.1% reported ferritin decreased, 25.7% showed unsaturated iron binding capacity increased, and 17.1% had neutrophil count decreased. Cmax exhibited a dose-disproportionate rise from a geometric mean of 525 pg/mL with 0.2 µg/kg PEG-EPO to 23196 pg/mL with 4.8 µg/kg PEG-EPO. The mean t1/2 ranged between 82.4 ± 21.3 h with 0.4 µg/kg PEG-EPO and 160.6 ± 65.7 h with 1.6 µg/kg PEG-EPO. AUC0-inf displayed a largely dose-proportional rise from 226264.5 pg*h/mL with 0.2 µg/kg PEG-EPO to 5206434.0 pg*h/mL with 4.8 µg/kg PEG-EPO. The absolute reticulocyte count increased with escalating doses of PEG-EPO, with the mean maximal change from baseline between 3.2 ± 1.5*10^10/L (Q1,Q3 1.8-3.6*10^10/L) with PEG-EPO 0.2 µg/kg and 9.3 ± 4.0*10^10/L (Q1,Q3 6.2-13.5*10^10/L) with 3.6 µg/kg PEG-EPO. The mean maximal change from baseline in the mean hemoglobin content ranged between 5.9 ± 4.4 g/L (Q1,Q3 3.5,7.0) with 0.2 µg/kg PEG-EPO and 15.4 ± 8.7 g/L (Q1,Q3 10.5,20.0) with 2.4 µg/kg PEG-EPO.
CONCLUSIONS: This trial demonstrated that PEG-EPO was safe and tolerable in healthy subjects. The subcutaneous route of administration allows outpatient treatment and the pharmacokinetics characteristics of PEG-EPO support less frequent dosing regimens and effective treatment for chronic kidney disease patients with anemia.
BACKGROUND: clinicaltrials.gov identifier: NCT03657238.

With significant advancements in understanding gene functions and therapy, the potential misuse of gene technologies, particularly in the context of sports through gene doping (GD), has come to the forefront. This raises concerns regarding the need for point-of-care testing of various GD candidates to counter illicit practices in sports. However, current GD detection techniques, such as PCR, lack the portability required for on-site multiplexed detection. In this study, we introduce an integrated microfluidics-based chip for multiplexed gene doping detection, termed MGD-Chip. Through the strategic design of hydrophilic and hydrophobic channels, MGD-Chip enables the RPA and CRISPR-Cas12a assays to be sequentially performed on the device, ensuring minimal interference and cross-contamination. Six potential GD candidates were selected and successfully tested simultaneously on the platform within 1 h. Demonstrating exceptional specificity, the platform achieved a detection sensitivity of 0.1 nM for unamplified target plasmids and 1 aM for amplified ones. Validation using mouse models established by injecting IGFI and EPO transgenes confirmed the platform\'s efficacy in detecting gene doping in real samples. This technology, capable of detecting multiple targets using portable elements, holds promise for real-time GD detection at sports events, offering a rapid, highly sensitive, and user-friendly solution to uphold the integrity of sports competitions.

We aimed to compare the clinical efficacy and safety of roxadustat with erythropoiesis-stimulating agents, particularly erythropoietin (EPO), in the treatment of maintenance hemodialysis patients with renal anemia. A prospective cohort study was carried out at the Nephrology Department of the Nantong First People\'s Hospital and Nantong University Affiliated Hospital from December 2020 to December 2021. We compared hemoglobin (Hb) levels, serum ferritin (SF) levels, and adverse cardiovascular events between the roxadustat and EPO groups at 1, 3, and 6 months into the treatment. A total of 209 patients participated in the study, with 112 in the roxadustat group and 97 in the EPO group. At baseline, no statistically significant differences were observed between the 2 groups in terms of age, gender, weight, dialysis modality and duration, previous EPO dosage, Hb levels, SF levels, transferrin saturation, heart function classification, and blood pressure levels (P > .05). After 1 month, Hb levels in the roxadustat group were significantly higher than those in the EPO group (P < .05). However, no statistically significant differences were found between the 2 groups at 3 and 6 months (P > .05). Additionally, there were no significant differences in SF levels and the occurrence of adverse cardiovascular events between the 2 groups after treatment (P > .05). Roxadustat was superior to EPO in the initial treatment phase, while its cardiovascular safety was comparable to that of EPO.

BACKGROUND: Jian-Pi-Yi-Shen (JPYS) formula is an effective herbal therapy against renal injury, and JPYS has been clinically applied to ameliorate chronic kidney disease (CKD) and CKD-associated anemia. Increasing evidence supports the link between renal fibrosis and anemia in CKD. JPYS possessed anti-fibrosis effects in experimental CKD. Nevertheless, research on the mechanisms of JPYS in ameliorating renal anemia (RA) through suppressing renal fibrosis remains to be clarified.
OBJECTIVE: Our study here was carried out to investigate the mechanisms of JPYS in protecting against RA.
METHODS: An adenine-induced anemia model in rats with CKD at three different time points was established, and bio-samples taken from each group were analyzed. Biochemical analysis was employed to detect kidney function and hematological parameters. Masson staining was used to evaluate renal fibrosis of rats. Western blot and immunohistochemistry were utilized to evaluate the expressions of fibrotic markers, erythropoietin (EPO) and hypoxia inducible factor-2α (HIF-2α) in the kidneys of rats. Subsequently, transcriptomic analysis was conducted to disclose the possible mechanisms of JPYS in treating RA. Finally, the expression levels of key targets were analyzed and validated by using Western blot and enzyme-linked immunosorbent assay (ELISA).
RESULTS: JPYS treatment improved kidney function, suppressed renal fibrosis and enhanced hematological parameters in CKD rats. Moreover, JPYS treatment restored the increased expression levels of fibrotic markers and the declined EPO with time dependence. In parallel, data indicated JPYS treatment stimulated the translocation of HIF-2α into nucleus in the renal interstitium and thus promoted the expression of EPO. Transcriptomic profiling disclosed that activations of both nuclear factor kappa B (NF-κB) and transforming growth factor-β (TGF-β)/Smad pathways were closely associated with RA. Ultimately, experimental validation results presented that the increased expressions of target proteins from the above-mentioned two pathways in the kidneys were decreased significantly after JPYS treatment.
CONCLUSIONS: Our findings suggest that JPYS may improve RA by alleviating renal fibrosis, and the mechanisms of which involve in inhibiting the NF-κB and TGF-β/Smad pathways.

UNASSIGNED: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week).
UNASSIGNED: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO.
UNASSIGNED: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased.
UNASSIGNED: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Cardiac arrest is a common and fatal emergency situation. Recently, an increasing number of studies have shown that anemia in patients with cardiac arrest is closely related to high mortality rates and poor neurological outcomes. Anemia is prevalent among patients with post-cardiac arrest syndrome (PCAS), but its specific pathogenesis remains unclear. The mechanisms may involve various factors, including reduced production of erythropoietin, oxidative stress/inflammatory responses, gastrointestinal ischemic injury, hepcidin abnormalities, iatrogenic blood loss, and malnutrition. Measures to improve anemia related to cardiac arrest may include blood transfusions, administration of erythropoietin, anti-inflammation and antioxidant therapies, supplementation of hematopoietic materials, protection of gastrointestinal mucosa, and use of hepcidin antibodies and antagonists. Therefore, exploring the latest research progress on the mechanisms and treatment of anemia related to cardiac arrest is of significant guiding importance for improving secondary brain injury caused by anemia and the prognosis of patients with cardiac arrest.
心脏骤停是一种常见且致命的紧急情况。近来，越来越多的研究表明心脏骤停患者发生贫血与高病死率及神经功能预后差密切相关。在心脏骤停后综合征(post-cardiac arrest syndrome，PCAS)患者中普遍存在贫血，但具体发病机制不清。机制可能涉及多种因素，包括促红细胞生成素产生减少、氧化应激/炎症反应、胃肠道缺血性损伤、铁调素异常、医源性失血及营养不良等，可通过输血，给予促红细胞生成素，抗炎，抗氧自由基，补充造血原料，保护胃肠道黏膜，使用铁调素抗体及拮抗剂等措施来改善心脏骤停后相关性贫血。因此，探讨心脏骤停后相关性贫血的机制及治疗的最新研究进展，对于改善贫血导致的继发性脑损伤以及心脏骤停患者的预后具有重要的指导意义。.