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Bovine hemolytic anemia has a negative impact on animal welfare and productivity due to its associated clinical symptoms. Hemolysis is generally known to cause reticulocytosis, increased indirect bilirubin, decreased concentration of haptoglobin, and increased lactate dehydrogenase. Additionally, tissue hypoperfusion due to concomitant anemia increases blood lactate concentration. However, few studies have reported the correlation between these indicators and hemolytic anemia in cattle. We expected that alterations in hematological and biochemical parameters could identify cattle with hemolytic anemia. Therefore, in addition to reporting differences in indicators according to hemolytic anemia, this study aimed to derive indicators and set criteria for identification of bovine hemolytic anemia. In cattle with hemolytic anemia, reticulocytosis, increased indirect bilirubin, and increased L-lactate were observed, and the correlation of these indicators with hematocrit (HCT) was confirmed. And since HCT alone has limitations in identifying hemolytic anemia, we suggest additional criteria to identify hemolytic anemia in cattle.

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BACKGROUND: In light of prolonged hypoxia, children with cyanotic heart disase (CHD) are at a high risk of developing iron deficiency iron deficiency (ID) and iron deficiency anemia (IDA). Reticulocyte hemoglobin equivalent (Ret-He) is a novel and dependable indicator for assessing iron status. However, there has been no previous study regarding cut-off value in pediatric CHD group. The purpose of this study is to assess the role of Ret-He and to establish cut-off points in the diagnosis of iron deficiency and IDA in pediatric cyanotic heart disease. METHOD: This study was conducted in two tertiary hospitals in Jakarta, Indonesia. 59 children with CHD, aged 3 months to 18 years, were enrolled consecutively. To determine iron status, hematological parameters (hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin) and biochemical parameters for iron status (serum ferritin, transferrin saturation) were analysed and compared to Ret-He levels. The receiver operating characteristic (ROC) analysis was performed for the Ret-He cut-off points for ID and IDA. Sensitivity, specificity, positive and negative predictive value were calculated for each cut-off point. RESULT: Normal iron status was identified in 27 (45.8%) subjects, ID in 8 (13.5%) subjects, and IDA 24 (40.7%) subjects. The ID cut-off value for Ret-He is 28.8 pg (sensitivity 75%, specificity 85.2%, PPV 60%, NPV 92%, and AUC 0.828) and the Ret-He cut-off point for IDA is 28.15 pg (sensitivity 75%, specificity 88.9%, PPV 85.7%, NPV 80%, and AUC 0.824). Hemoglobin should be used in conjunction with Ret-He. ID might be detected in this cohort with Ret-He 28.8 pg and hemoglobin > 16,5 g/dL. While Ret-He 28.15 pg or Ret-He 28.15-28.8 pg with hemoglobin 16.5 g/dL could be used to diagnose IDA. CONCLUSION: The reticulocyte hemolgobin equivalent could be utilised as an iron status parameter in pediatric CHD, with a cut-off value of 28.8 pg for ID and 28.15 pg for IDA.

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Anemia Ferropénica , Cardiopatías Congénitas , Hemoglobinas , Deficiencias de Hierro , Reticulocitos , Humanos , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/sangre , Anemia Ferropénica/etiología , Preescolar , Masculino , Indonesia , Femenino , Lactante , Niño , Hemoglobinas/análisis , Reticulocitos/metabolismo , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/diagnóstico , Adolescente , Cianosis/sangre , Cianosis/etiología , Cianosis/diagnóstico , Curva ROC , Sensibilidad y Especificidad , Biomarcadores/sangre , Hierro/sangre , Ferritinas/sangre

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Background and Aim: Anemia, a clinical condition characterized by reduced erythrocytes, is often observed in cats. Regeneration indicates that the bone marrow can respond appropriately to anemia. The absolute reticulocyte count is the reference for differentiating regenerative and non-regenerative anemia, while red blood cell (RBC) indices and morphology provide supplementary information. This study aimed to identify anemia types and establish the most reliable RBC indices and morphology methods in agreement with the reference method. Materials and Methods: One hundred forty-five cases of cat anemia were prospectively classified using two methods: RBC indices and RBC morphology, and subsequently compared with the absolute reticulocyte count. Results: Based on RBC indices assessment, 27 cases (19%) exhibited regenerative anemia. Based on RBC morphology, 29 (20%) cases were identified as having regenerative anemia. Using the reticulocyte absolute count as a reference method, 34 (23.4%) cases of regenerative anemia were identified. The findings indicated that RBC indices and RBC morphology did not align in evaluating medullary regeneration and that there is a good degree of agreement between RBC morphology assessment and the reticulocyte absolute count in identifying regenerative anemias. Conclusion: Blood smear analysis of RBC morphology was more dependable for classifying regenerative anemia than RBC indices. Further studies should be conducted with a larger number of animals and that allow the identification of the cause of anemia and the monitoring of the animal.

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BACKGROUND: Nearly 58% of very low birth weight (VLBW) infants receive at least one red blood cell transfusion, which is not without risk. Reticulocyte fluorescence (RF) indicates the degree of cell maturation. The greater the fluorescence, the greater the immaturity of the reticulocytes. AIM: To evaluate RF as a marker of reticulocyte maturity and to investigate its predictive value for transfusion requirement in VLBW infants. METHODS: Complete blood count was performed at 1, 7, 14, 21, and 28 d of age in 104 VLBW infants at the University Hospital of Parma. Iron supplementation was started at 15 d of life. The infants were divided into two groups: those who required transfusion after 28 d of life. (Tr) and those who did not (NTr). RESULTS: Twenty-seven of 104 newborns required a red blood cell transfusion after 28 d of life (Tr group). At 14 d of life, the percentage of high fluorescence reticulocyte (HFR) was significantly higher in the r group than in infants who did not receive any transfusion (NTr groups): 18.5 vs. 5%, p = 0.002. The ROC curve (AUC 74%) revealed an HFR cut-off value of 16.5% as a predictor of the need for red blood cell (RBC) transfusion. CONCLUSIONS: Reticulocyte maturation at 14 d of life is clinically useful for estimating the qualitative impairment of erythropoiesis and predicts the risk of RBC transfusion in VLBW infants. The data suggest the need for tailored iron integration in VLBW infants to improve the quality of hematopoiesis and reduce the risk of blood transfusion.

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BACKGROUND: Anemia-associated chronic kidney disease increases in more advanced stages with a subsequent acceleration in renal impairment progressing to end-stage renal disease. Although hepcidin and erythroferrone have been described as novel biomarkers of iron metabolism, there is still an area of ambiguity regarding iron utility in anemia-associated end-stage renal disease. OBJECTIVES: This study aims to determine the correlations between erythropoietin, erythroferrone, and hepcidin-25 in hemodialysis, and to evaluate the clinical utility of the hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness compared to reticulocyte maturation parameters. METHODS: Serum erythropoietin, erythroferrone, and hepcidin-25 levels in 35 dialysis-dependent patients on a maintenance dose of a short-acting erythropoiesis-stimulating agent were consequently assessed on Days 0, 5, and 7. The erythropoiesis activity was monitored by measuring the increment in reticulocyte maturation parameters. RESULTS: Though the effectiveness of erythropoiesis in these patients was not associated with the hepcidin-25/erythroferrone ratio, it was lower among those with effective erythropoiesis than those with ineffective erythropoiesis. The effective group showed a statistically significant increase in reticulocyte maturation parameters compared to the ineffective group. CONCLUSIONS: The findings show the pathogenesis of iron homeostasis in hemodialysis, the validity of hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness, and the advantageous monitoring of reticulocyte maturation measures to improve management of anemia-associated chronic kidney disease.

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Purpose: The main aim of this study was to compare and analyze hematological profiles using menstrual blood, as an alternative to peripheral blood. Patients and Methods: This study used menstrual and peripheral blood samples from women who were menstruating. The design of this research is analytical observational. Results: Menstrual blood can show an overall hematological profile similar to peripheral blood. Data shows the detection of blood component parameters, white blood cells and reticulocytes in MB with a range within and outside normal blood. Data on MB that show higher values (WBC, MCH, MCHC, PLT, RDW-CV, PDW, MPV, P-LCR, PCT, neutrophils, lymphocytes, monocytes, basophils, reticulocytes, LFR, Ret-He) and lower values lower (RBC, HGB, HCT, MVC, RDW-SD, Eosinophils, IRF, MFR, HFR) when compared with peripheral blood controls. The hematological profiles of Menstrual and peripheral blood showed significant differences (p < 0.01) for several parameters, while several other parameters did not show significant differences (p > 0.05) according to the Wilcoxon test. Conclusion: All hematological profile parameters were detected in menstrual blood. The new concept that menstrual blood can be used as a supporting medium for hematological examinations opens up opportunities for developing independent hematological detection tools in productive women.

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BACKGROUND AND OBJECTIVES: Women are more prone to iron deficiency (ID) anemia when pregnant. The diagnostic use of mean reticulocyte volume (MRV) in identifying ID anemia during pregnancy has not been thoroughly investigated. The objective of this study is to evaluate the effectiveness of MRV in diagnosing ID in pregnant women. METHODS AND STUDY DESIGN: Firstly, MRV of 20 healthy female volunteers (healthy group) was measured on specific days for one month. Subsequently, clinical data from 724 pregnant women were thoroughly examined. These women were divided into two groups: 282 with ID (research group) and 442 without ID (control group). Parameters such as MRV, reticulocyte hemoglobin equivalent (RHE), red blood cell volume distribution width-standard deviation (RDW-SD), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), reticulocyte count (RET), MRV/MCV ratio, and serum ferritin (SF) were analyzed and compared. RESULTS: MRV remained consistent over a period of one month for 20 healthy individuals. In addition, there were significant differences in MRV, RHE, RDW-SD, MCV, MCH, MCHC, HCT, RET, and MRV/MCV between the research group and control group. The receiver operating characteristic (ROC) analysis showed that the areas under the curve (AUCs) for these measures were as follow: 0.840, 0.837, 0.676, 0.654, 0.639, 0.602, 0.571, 0.550, and 0.816, respectively. Ultimately, there was a substantial disparity in MRV prior to and following therapy with oral iron treatments. CONCLUSIONS: In healthy women, MRV remains stable and is a reliable ID marker, which can be used to assess oral iron treatment effectiveness during pregnancy.

Asunto(s)

Anemia Ferropénica , Reticulocitos , Humanos , Femenino , Embarazo , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/sangre , Adulto , Índices de Eritrocitos , Recuento de Reticulocitos , Adulto Joven , Complicaciones Hematológicas del Embarazo/sangre , Complicaciones Hematológicas del Embarazo/diagnóstico

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PURPOSE: 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. FINDINGS: 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. IMPLICATIONS: 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. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03657238.

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Relación Dosis-Respuesta a Droga , Eritropoyetina , Voluntarios Sanos , Polietilenglicoles , Humanos , Masculino , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Polietilenglicoles/farmacocinética , Femenino , Adulto , Método Doble Ciego , Eritropoyetina/farmacocinética , Eritropoyetina/administración & dosificación , Eritropoyetina/efectos adversos , Adulto Joven , Hemoglobinas/análisis , Persona de Mediana Edad , Recuento de Reticulocitos , Inyecciones Subcutáneas , Área Bajo la Curva

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Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.

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Objective: The purpose of this study was to evaluate the methodological comparison of reticulocytes by using the intelligent learning system Faster R-CNN, a set of reticulocyte image detection systems developed using deep neural networks. Methods: We selected 59 EDTA-K2 anticoagulated whole blood samples and calculated the RET% using seven different Sysmex XN full-automatic hematology analyzers with Faster R-CNN in the laboratory. We compared and evaluated the methods and statistically analyzed the correlation between the various test results. Results: The results indicated a high degree of consistency between the seven Sysmex XN full-automatic hematology analyzers and Faster R-CNN in detecting RET%. The correlation coefficients were 0.987, 0.984, 0.986, 0.987, 0.987, 0.988, and 0.986, respectively. Conclusion: We found that the Sysmex XN full-automatic hematology analyzers in our laboratory using the Faster R-CNN system met the requirements of the methodological comparison of reticulocyte detection and this intelligent learning system can be a useful clinical tool.

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INTRODUCTION: Reticulocyte count and novel derived parameters provide insight into the effectiveness of erythropoiesis and may be useful tools in the classification and diagnosis of anemias. However, there is no standardisation, so we consider it necessary that each laboratory evaluates the parameters according to its own methodology and instrumentation and establishes its own reference ranges. Our aim was to establish the reference intervals (RIs) of reticulocyte profile provided by the Beckman Coulter DxH 900 haematological autoanalyzer in our reference population. METHODS: One hundred and seventy-five healthy adults (18 to 62 years) were included. Subjects were collected from the blood donation centre of the Hospital Clínico San Carlos (Madrid, Spain) upon informed consent. Whole blood was collected and assayed for 14 haematological parameters on the Beckman Coulter DxH 900 analyzer in the haematology laboratory of the Clinical Analysis Department. RIs were established as per Clinical and Laboratory Standards Institute EP28-A3c guidelines using three different statistical approaches. RESULTS: RIs estimated using the non-parametric method and the Harrell-Davis bootstrap method were very similar. RIs estimated by the robust method were narrower. Gender partitioning was required for two haematological parameters (low haemoglobin density (LHD) and microcytic anaemia factor (MAF)). The rest of the parameters did not need to be partitioned according to Lahti's method. CONCLUSION: RIs have been established for 14 hematologic parameters of the reticulocyte profile for the Beckman Coulter DxH 900 haematology analyzer using a healthy cohort of adult subjects.

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Red blood cell (RBC) transfusion, limited by patient alloimmunization, demands accurate blood group typing. The Rh system requires specific attention due to the limitations of serological phenotyping methods. Although these have been compensated for by molecular biology solutions, some RhCE ambiguities remain unresolved. The RHCE mRNA length is compatible with full-length analysis and haplotype discrimination, but the RHCE mRNA analyses reported so far are based on reticulocyte isolation and molecular biology protocols that are fastidious to implement in a routine context. We aim to present the most efficient reticulocyte isolation method, combined with an RT-PCR sequencing protocol that embraces the phasing of all haplotype configurations and identification of any allele. Two protocols were tested for reticulocyte isolation based either on their size/density properties or on their specific antigenicity. We show that the reticulocyte sorting method by antigen specificity from EDTA blood samples collected up to 48 h before processing is the most efficient and that the combination of an RHCE-specific RT-PCR followed by RHCE allele-specific sequencing enables analysis of cDNA RHCE haplotypes. All samples analyzed show full concordance between RHCE phenotype and haplotype sequencing. Two samples from the immunohematology laboratory with ambiguous results were successfully analyzed and resolved, one of them displaying a novel RHCE allele (RHCE*03 c.340C>T).

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Alelos , Haplotipos , Sistema del Grupo Sanguíneo Rh-Hr , Humanos , Sistema del Grupo Sanguíneo Rh-Hr/genética , Reticulocitos/metabolismo , ARN Mensajero/genética , Transfusión Sanguínea/métodos , Fenotipo

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Global prevalence of hypertension is on the rise, burdening healthcare, especially in developing countries where infectious diseases, such as malaria, are also rampant. Whether hypertension could predispose or increase susceptibility to malaria, however, has not been extensively explored. Previously, we reported that hypertension is associated with abnormal red blood cell (RBC) physiology and anemia. Since RBC are target host cells for malarial parasite, Plasmodium, we hypothesized that hypertensive patients with abnormal RBC physiology are at greater risk or susceptibility to Plasmodium infection. To test this hypothesis, normotensive (BPN/3J) and hypertensive (BPH/2J) mice were characterized for their RBC physiology and subsequently infected with Plasmodium yoelii (P. yoelii), a murine-specific non-lethal strain. When compared to BPN mice, BPH mice displayed microcytic anemia with RBC highly resistant to osmotic hemolysis. Further, BPH RBC exhibited greater membrane rigidity and an altered lipid composition, as evidenced by higher levels of phospholipids and saturated fatty acid, such as stearate (C18:0), along with lower levels of polyunsaturated fatty acid like arachidonate (C20:4). Moreover, BPH mice had significantly greater circulating Ter119+ CD71+ reticulocytes, or immature RBC, prone to P. yoelii infection. Upon infection with P. yoelii, BPH mice experienced significant body weight loss accompanied by sustained parasitemia, indices of anemia, and substantial increase in systemic pro-inflammatory mediators, compared to BPN mice, indicating that BPH mice were incompetent to clear P. yoelii infection. Collectively, these data demonstrate that aberrant RBC physiology observed in hypertensive BPH mice contributes to an increased susceptibility to P. yoelii infection and malaria-associated pathology.

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Eritrocitos , Hipertensión , Malaria , Plasmodium yoelii , Animales , Malaria/inmunología , Malaria/parasitología , Malaria/complicaciones , Malaria/sangre , Malaria/fisiopatología , Ratones , Eritrocitos/parasitología , Eritrocitos/metabolismo , Susceptibilidad a Enfermedades , Masculino , Anemia/parasitología , Modelos Animales de Enfermedad , Hemólisis

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Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly for neurodevelopment. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supplementation strategy for full-term and preterm infants that does not consider individual variation in body iron status and thus could lead to undertreatment or overtreatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with a risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcomes in perinatal iron deficiency.

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Encefalopatías , Deficiencias de Hierro , Enfermedades Neuromusculares , Recién Nacido , Lactante , Femenino , Embarazo , Humanos , Niño , Recien Nacido Prematuro , Hierro , Biomarcadores , Encéfalo

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The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin sensitive. Antibodies against band3-P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and Plasmodium cynomolgi MSP1P-19 to reticulocytes, while MSP1P-19 proteins inhibited Plasmodium falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19.

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Antígenos CD , Plasmodium vivax , Proteínas Protozoarias , Receptores de Transferrina , Reticulocitos , Plasmodium vivax/metabolismo , Plasmodium vivax/genética , Reticulocitos/metabolismo , Reticulocitos/parasitología , Humanos , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/genética , Antígenos CD/metabolismo , Antígenos CD/genética , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Proteína 1 de Intercambio de Anión de Eritrocito/genética , Unión Proteica , Proteína 1 de Superficie de Merozoito/metabolismo , Proteína 1 de Superficie de Merozoito/genética , Malaria Vivax/parasitología , Malaria Vivax/metabolismo , Animales

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SUMMARYMalaria remains one of the biggest health problems in the world. While significant reductions in malaria morbidity and mortality had been achieved from 2000 to 2015, the favorable trend has stalled, rather significant increases in malaria cases are seen in multiple areas. In 2022, there were 249 million estimated cases, and 608,000 malaria-related deaths, mostly in infants and children aged under 5 years, globally. Therefore, in addition to the expansion of existing anti-malarial control measures, it is critical to develop new tools, such as vaccines and monoclonal antibodies (mAbs), to fight malaria. In the last 2 years, the first and second malaria vaccines, both targeting Plasmodium falciparum circumsporozoite proteins (PfCSP), have been recommended by the World Health Organization to prevent P. falciparum malaria in children living in moderate to high transmission areas. While the approval of the two malaria vaccines is a considerable milestone in vaccine development, they have much room for improvement in efficacy and durability. In addition to the two approved vaccines, recent clinical trials with mAbs against PfCSP, blood-stage vaccines against P. falciparum or P. vivax, and transmission-blocking vaccine or mAb against P. falciparum have shown promising results. This review summarizes the development of the anti-PfCSP vaccines and mAbs, and recent topics in the blood- and transmission-blocking-stage vaccine candidates and mAbs. We further discuss issues of the current vaccines and the directions for the development of next-generation vaccines.

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Anticuerpos Monoclonales , Vacunas contra la Malaria , Vacunas contra la Malaria/inmunología , Humanos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Plasmodium falciparum/inmunología , Malaria/prevención & control , Malaria/inmunología , Malaria Falciparum/prevención & control , Malaria Falciparum/inmunología , Anticuerpos Antiprotozoarios/inmunología , Proteínas Protozoarias/inmunología , Ensayos Clínicos como Asunto

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Background: Cancer-related anemia (CRA) is a functional iron deficient anemia, and the early diagnosis will improve the prognosis of the patients. This prospective study aimed to investigate the utility of mean reticulocyte volume (MRV) in the early diagnosis of CRA. Methods: A total of 284 first-diagnosed cancer patients were enrolled, and the subjects were assigned anemia and non-anemia groups by hemoglobin (Hb) concentrations. The mature RBC and reticulocyte indices were detected with BC-7500 blood analyzer, and the MRV, reticulocyte hemoglobin (RHE) content, and reticulocyte production index (RPI) were obtained. ROC curves were constructed in identifying anemia diagnosed by the combination of RHE and RPI. An adjusted multivariate analyse and quartiles were used to assess the associations of MRV with early CRA diagnosed by combining RBC indices (MCV, MCH and MCHC), respectively. Results: No statistical differences were observed in MCV, RHE and MRV levels between anemia and non-anemia subjects (p > 0.05). MRV exhibited a complete or high correlation with the RHE levels (r = 1.000, p < 0.001), or MCV, MCH, and MCHC in anemia patients (R: 0.575-0.820, p < 0.001). ROC curves analyse indicated a highest area under curve of 0.829 (95% CI [0.762-0.895]) and 0.884 (95% CI [0.831-0.936]) for MRV in identifying anemia in male and female patients, respectively (p < 0.001). When the optimal cutoff values of MRV were set at 100.95 fl in males and 98.35 fl in females, the sensitivity and specificity were 1.00 and 0.68, and 1.00 and 0.73, respectively. The regression analyse showed that, when being as a categorical variable, MRV showed an odds ratio of 19.111 (95% CI [6.985-52.288]; p < 0.001) for the incidence of CRA. The incidence of overall anemia demonstrated a more significant decrease trend along with the increase of MRV quartiles (p-trend < 0.001). Conclusion: This study revealed that the MRV can be used as a convenient and sensitive index in early diagnosis of cancer-related anemia, and decreased MRV level may be the powerful predictor of overt anemia in cancer patients.

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Anemia , Neoplasias , Humanos , Femenino , Masculino , Reticulocitos , Detección Precoz del Cáncer , Estudios Prospectivos , Anemia/diagnóstico , Hemoglobinas , Neoplasias/complicaciones

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OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening hematological disorder. Early differentiation between TTP and primary immune thrombocytopenia (ITP) accompanied by anemia is crucial to initiate an appropriate therapeutic strategy. The objective of this study was to evaluate the predictive value of red blood cell lifespan (RBCLS), determined using the carbon monoxide breath test, in the differential diagnosis of these two diseases. METHODS: We conducted a retrospective analysis of 23 patients with TTP and 32 patients with ITP accompanied by anemia. RBCLS measurements were compared and evaluated between these two patient groups. RESULTS: TTP patients had a significantly shorter mean RBCLS (20 ± 8 days) than patients with ITP accompanied by anemia (77 ± 22 days, P < 0.001) and healthy controls (114 ± 25 days, P < 0.001). In TTP patients, RBCLS showed a significant negative correlation with reticulocyte percentage and lactic dehydrogenase levels (P < 0.001). When using a standard baseline of 75 days, RBCLS demonstrated a sensitivity of 100% and specificity of 53.1% in identifying TTP. The diagnostic accuracy could reach 93% by excluding the impact of gastrointestinal bleeding. By employing the Receiver Operator Characteristics (ROC) curve, the area under the curve for RBCLS was 0.985 (95% CI: 0-1, P < 0.01) in predicting TTP, with an optimal cut-off value of 32 days, and sensitivity and specificity of 95.7% and 96.9%, respectively. CONCLUSIONS: Our study proposes a simple and accessible method for evaluating RBCLS to differentiate between TTP and ITP accompanied by anemia.

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Anemia , Púrpura Trombocitopénica Idiopática , Púrpura Trombocitopénica Trombótica , Humanos , Monóxido de Carbono , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/diagnóstico , Estudios Retrospectivos , Pruebas Respiratorias

RESUMEN

The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxiredoxin 2 (Prx2) are particularly important in erythroid cells. Reticulocytes and other erythroid precursors may adapt their biosynthetic mechanisms to cell defects or to changes in the bone marrow environment. Our aim was to perform a comparative study of the mRNA levels of CAT, GPX1, PRDX2 and SOD1 in reticulocytes from healthy individuals and from patients with hereditary spherocytosis (HS), sickle cell disease (SCD) and ß-thalassemia (ß-thal), and to study the association between their transcript levels and the reticulocyte maturity indices. In controls, the enzyme mRNA levels were significantly correlated with reticulocyte maturity indices for all genes except for SOD1. HS, SCD and ß-thal patients showed younger reticulocytes, with higher transcript levels of all enzymes, although with different patterns. ß-thal and HS showed similar reticulocyte maturity, with different enzyme mRNA levels; SCD and HS, with different reticulocyte maturity, presented similar enzyme mRNA levels. Our data suggest that the transcript profile for these antioxidant enzymes is not entirely related to reticulocyte maturity; it appears to also reflect adaptive mechanisms to abnormal erythropoiesis and/or to altered erythropoietic environments, leading to reticulocytes with distinct antioxidant potential according to each anemia.

Asunto(s)

Anemia de Células Falciformes , Esferocitosis Hereditaria , Talasemia beta , Humanos , Reticulocitos , Talasemia beta/genética , Antioxidantes , ARN Mensajero/genética , Superóxido Dismutasa-1 , Esferocitosis Hereditaria/genética , Anemia de Células Falciformes/genética

RESUMEN

Background/Objective: Reticulocyte hemoglobin content (MCHr) was recognized as a rapid and reliable marker for investigating iron deficiency (ID). We hypothesized that MCHr was associated with the risk of iron deficiency anemia in adults. Methods: This is a dual-center case-control study. A total of 806 patients and healthy individuals were recruited from Ruijin Hospital and Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine between January 2021 and December 2021. The participants were categorized into iron deficiency anemia (IDA) group (n = 302), non-IDA group (n = 366), and healthy control group (n = 138). According to the MCHr level, the participants were divided into two groups, i.e. normal MCHr (≥25 pg) and decreased MCHr (<25 pg) group. Multivariate logistic regression analysis and adjusted subgroup analysis were conducted to estimate the relative risk between MCHr and IDA, with confounding factors including age, sex, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), Hematocrit (HCT), serum iron (Fe), ferritin (Ferrit), and total iron binding capacity (TIBC). Results: Compared with the non-IDA, the MCHr level with IDA decreased significantly. ROC curve analysis showed that MCHr had the largest area under the AUC curve. After comprehensive adjustment for confounding factors, individuals with normal level of MCHr exhibited a decreased risk of IDA (OR = 0.68 [0.60, 0.77], P < 0.01), while the risk of IDA was up to 5 times higher for those with decreased MCHr. Conclusion: Our findings supported the hypothesis that MCHr was associated with the risk of IDA in adults and could serve as an indicator of IDA severity. MCHr holds clinical value as an auxiliary diagnostic indicator, providing valuable insights into whether invasive examinations are warranted in the assessment of IDA.