Blood Cells Molecules and Diseases最新文献

Background

Sickle Cell Anemia (SCA) is a monogenic disease, although its severity and response to treatment are very heterogeneous.

Objectives

This study aims to characterize a cohort of Angolan children with SCA and evaluate their response to hydroxyurea (HU) treatment and the potential side effects and toxicity.

Methods

The study enrolled 215 patients between 3 and 12 years old before and after the administration of HU, at a fix dose of 20 mg/kg/day for 12 months.

Results

A total of 157 patients started HU medication and 141 of them completed the 12-month treatment. After initiating HU treatment, the frequency of clinical events decreased (transfusions 53.4 %, hospitalizations 47.1 %). The response to HU medication varied among patients, with some experiencing an increase in fetal hemoglobin (HbF) of <5 %. The mean increase in HbF was 11.9 %, ranging from 1.8 % to 31 %. Responders to HU treatment were 57 %, inadequate responders 38.7 % and non-adherent 4.2 %. No clinical side effects related to HU were reported. Hematological toxicities were transient and reversible. Children naïve to HU and with lower HbF reported higher number of hospitalizations caused by malaria infection. During HU treatment, the frequency of malaria episodes did not appear to be affected by HbF levels.

Conclusions

the present study provided a valuable contribution to the understanding of the clinical and laboratory profiles of Angolan children with SCA. These findings support the evidence that the implementation of prophylactic measures and treatment with HU is associated with increased survival in children with SCA.

Peripheral blood smear examination is one of the basic steps in the evaluation of different blood cells. It is a confirmatory step after an automated complete blood count analysis. Manual microscopy is time-consuming and requires professional laboratory expertise. Therefore, the turn-around time for peripheral smear in a health care center is approximately 3–4 hours. To avoid the traditional method of manual counting under the microscope a computerized automation of peripheral blood smear examination has been adopted, which is a challenging task in medical diagnostics. In recent times, deep learning techniques have overcome the challenges associated with human microscopic evaluation of peripheral smears and this has led to reduced cost and precise diagnosis. However, their application can be significantly improved by the availability of annotated datasets. This study presents a large customized annotated blood cell dataset (named the Bio-Net dataset from healthy individuals) and blood cell detection and counting in the peripheral blood smear images. A mini-version of the dataset for specialized WBC-based image processing tasks is also equipped to classify the healthy and mature WBCs in their respective classes. An object detection algorithm called You Only Look Once (YOLO) with a refashion disposition has been trained on the novel dataset to automatically detect and classify blood cells into RBCs, WBCs, and platelets and compare the results with other publicly available datasets to highlight the versatility. In short the introduction of the Bio-Net dataset and AI-powered detection and counting offers a significant potential for advancement in biomedical research for analyzing and understanding biological data.

Dyslipidemia is frequently observed in polycystic ovarian syndrome (PCOS). Changes in plasma lipid levels potentially alter erythrocyte membrane lipid composition due to lack of inbuilt lipid synthesis machinery. Therefore, development of morphologically altered erythrocytes in PCOS patients with dyslipidemia is expected. However, this has not been established so far. So, we took this opportunity to explore the morphological alterations among dyslipidemic PCO women. We recruited thirty-five dyslipidemic PCOS women (satisfying Rotterdam criteria, without medication) and twenty-five age-matched healthy controls. Scanning electron microscopy revealed a significant increase in the number of stomatocytes, acanthocytes, and echinocytes in the PCO group. PCO group showed a considerable decrease in plasma antioxidant levels. Elevated lipid peroxidation, protein carbonylation, and decreased free thiol group in erythrocyte membrane in PCOS suggest oxidative degradation of the erythrocyte membrane. Elevated intracellular ROS levels, increased methemoglobin formation, and a decrease in NADPH methemoglobin reductase in PCOS also indicate altered physicochemical property of hemoglobin due to oxidative overload. Additionally, these patients exhibit a rise in erythrocyte membrane cholesterol and triglyceride, which promotes the membrane to become less fluidic and less fragile. Thus, these results corroborate a potential role in altering erythrocyte morphology among dyslipidemic PCO women.

Background

Haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PTCy) is an important therapeutic option for patients lacking an HLA-matched donor. However, the significance of CD34⁺ cell dose in grafts has not been fully elucidated.

Objective

We aimed to explore the impact of CD34⁺ cell dose on outcomes after haplo-PBSCT with PTCy.

Study Design

We retrospectively investigated 111 consecutive patients who underwent haplo-PBSCT with PTCy or HLA-matched PBSCT from related donors.

Results

There were no statistically significant differences in 3-year overall survival (p = 0.559) or progression-free survival (p = 0.974) between haplo-PBSCT and matched PBSCT. Delayed neutrophil engraftment and a lower incidence of graft-versus-host disease were observed in haplo-PBSCT. The median dose of CD34⁺ cells was 4.9 × 10⁶ /kg in 57 haplo-PBSCT and 4.5 × 10⁶ /kg in 54 matched PBSCTs. Importantly, patients who underwent haplo-PBSCT with the administration of CD34⁺ cell at a dose of ≥4.0 × 10⁶ /kg significantly had improved OS (p = 0.015) and decreased incidence of disease relapse (p = 0.001) without increasing incidence of GVHD.

Conclusion

Our data suggest that a higher dose of CD34⁺ cells in haplo-PBSCT with PTCy positively impacts the outcomes without an increase of GVHD.

Several syndromes affecting the red cell that mimic those induced by germline mutations may result from a somatic mutation that accompanies a myeloid malignancy. These syndromes are most notable in cases of myelodysplastic syndrome, but they are not limited to any one category of myeloid neoplasm. Their occurrence in males exceed the male predominance that is evident in myeloid neoplasms. The syndromes include disorders of globin chain synthesis (α- and β-thalassemia), heme synthesis (erythropoietic porphyria and erythropoietic uroporphyria), red cell membrane structure (elliptocytosis and spherocytosis), red cell enzyme activity (pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency) and lowered expression of red cell ABO blood group antigens. This historical review describes the path to uncovering these acquired syndromes and their causal somatic mutations, where known. These syndromes often go unrecognized because of the dominant concern of the primary neoplasm. They may add to the healthcare needs of the patient.

Red blood cells (RBC) from patients with sickle cell disease (SCD) have elevated calcium levels at baseline, which are further elevated upon deoxygenation. Here we examined baseline calcium levels and calcium flux in RBCs from a mouse model of SCD mice. We found that akin to humans with SCD, sickle (HbSS) Townes mice, have higher baseline levels and increased calcium flux in RBCs compared to control (HbAA) animals. As HbSS mice, unlike humans with SCD, have high mean corpuscular volume compared with HbAA, we highlight the importance of adjusting biochemical results to number of RBCs rather than hematocrit during the analysis and interpretation of the results. Our findings add to the face validity of humanized sickle cell mice and support its use for studies of RBC calcium flux in SCD.

Myeloproliferative neoplasms (MPN) are consolidated as a relevant group of diseases derived from the malfunction of the hematopoiesis process and have as a particular attribute the increased proliferation of myeloid lineage. Among these, chronic neutrophilic leukemia (CNL) is distinguished, caused by the T618I mutation of the CSF3R gene, a trait that generates ligand-independent receptor activation and downstream JAK2/STAT signaling. Previous studies reported that mutations in BCR::ABL1 and JAK2^V617F increased the expression of the aurora kinase A (AURKA) and B (AURKB) in Ba/F3 cells and their pharmacological inhibition displays antineoplastic effects in human BCR::ABL1 and JAK2^V617F positive cells. Delimiting the current scenario, aspects related to the AURKA and AURKB as a potential target in CSF3R^T618I-driven models is little known. In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3R^T618I mutation. AZD1152-HQPA and reversine demonstrated antineoplastic potential, causing a decrease in cell viability, clonogenicity, and proliferative capacity. At molecular levels, all inhibitors reduced histone H3 phosphorylation, aurora A inhibitor I and reversine reduced STAT5 phosphorylation, and AZD1152-HQPA and reversine induced PARP1 cleavage and γH2AX expression. Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL.