Blood Cells Molecules and Diseases最新文献

TAFRO syndrome is a rare systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The diagnosis of TAFRO syndrome can be challenging; however, prompt diagnosis is vital because TAFRO syndrome is a progressive and life-threatening disease. We have showcased five patients with TAFRO syndrome who had similar bone marrow (BM) findings that could be considered the findings that characterize TAFRO syndrome. All patients were treated with corticosteroids and tocilizumab; three of the five patients (60 %) responded positively to the treatment. The unique BM findings observed in this study were megakaryocytes with distinct multinuclei and three-dimensional and indistinct bizarre nuclei (“dysmorphic megakaryocyte”), similar to the megakaryocyte morphology observed in myeloproliferative neoplasms (MPNs). Notably, dysmorphic megakaryocytes were observed in all five cases, whereas only two of the five patients tested positive for reticulin myelofibrosis, and three of the five patients had megakaryocytic hyperplasia, which are considered typical findings of TAFRO syndrome. Thus, the BM findings of dysmorphic megakaryocytes could help in the correct and immediate diagnosis of TAFRO syndrome.

This retrospective study at Beijing Children's Hospital (2020–2023) analyzed surgical procedures and complications in 24 pediatric hemophilia patients undergoing Totally Implantable Venous Access Port (TIVAP) insertion, primarily in the right jugular vein (RJV). We detailed the surgical process, including patient demographics and intraoperative imaging use. The choice of the RJV for TIVAP placement was influenced by its larger diameter and superficial anatomical position, potentially reducing risks like thrombosis and infection. Our findings support the RJV as a safer alternative for port placement in pediatric patients, aligning with current literature. Statistical analysis revealed no significant correlation between complications and baseline characteristics like weight and diagnosis type. However, the length of hospital stay and implant brand were significant risk factors for catheter or port displacement and removal. The limited patient number may introduce bias, suggesting a need for further studies with larger samples. Despite a 14.7 %–33 % complication rate and 5 port removals, the advantages of TIVAP, including reliable venous access, reduced discomfort, and treatment convenience, were evident. Most complications improved with symptomatic treatment, and there were no deaths due to port-related complications, underscoring the impact of TIVAP on improving pediatric hemophilia treatment.

This study aimed to investigate the mechanism of the apoptosis of erythroblasts in rat bone marrow after the exposure to hypobaric hypoxia. Male SD rats were randomly divided into three groups. The hypoxic group was kept in a hypobaric hypoxia chamber at a simulated altitude of 5000 m for 7 and 28 days, respectively. The control group was kept at an altitude of 2260 m. We found that myeloid: erythroid (M:E) ratio was significantly lower after hypoxia exposure and the proportions of polychromatic erythroblasts and orthochromatic erythroblasts significantly increased compared to control group, along with significant increase in the proportion of CD71+ cells and apoptosis rate. The expression levels of caspase-3, Bax, and Cyt-C in CD71+ cells were higher after hypoxia exposure than those in control group, while there was no significant difference in the expression levels of TNFR and Fas. In conclusion, after exposure to hypobaric hypoxia the proliferation of peripheral blood and bone marrow erythroblasts in rats increased, and apoptosis also increased, indicating that bone marrow erythroblasts in rats is regulated by both proliferation and apoptosis, and the mitochondrial pathway is one of the important pathways for apoptosis.

We conducted a retrospective cohort study on 663 transfusion-dependent β-thalassemia patients receiving the same iron chelation monotherapy with deferoxamine, deferiprone, or deferasirox for up to 10 years (median age 31.8 years, 49.9 % females). Patients on all three iron chelators had a steady and significant decline in serum ferritin over the 10 years (median deferoxamine: −170.7 ng/mL, P = 0.049, deferiprone: −236.7 ng/mL, P = 0.001; deferasirox: −323.7 ng/mL, P < 0.001) yet had no significant change in liver iron concentration or cardiac T2*; while noting that patients generally had low hepatic and cardiac iron levels at study start. Median absolute, relative, and normalized changes were generally comparable between the three iron chelators. Patients receiving deferasirox had the highest morbidity and mortality-free survival probability among the three chelators, although the difference was only statistically significant when compared with deferoxamine (P = 0.037). On multivariate Cox regression analysis, there was no significant association between iron chelator type and the composite outcome of morbidity or mortality. In a real-world setting, there is comparable long-term iron chelation effectiveness between the three available iron chelators for patients with mild-to-moderate iron overload.

Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2–3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.

Background

Immune dysregulation is crucial in the pathogenesis of acquired aplastic anaemia (aAA). There is paucity of data regarding correlation of baseline cytokine profile with treatment response in aAA.

Objective

Present prospective case-control study aimed to correlate the baseline cytokines in patients with aAA with the treatment response.

Methods

Fifty-one patients with newly-diagnosed aAA > 13 years of either sex were enrolled over 1.5 years. Twenty age-and sex-matched healthy controls (HC) were also included. The cytokine profile (IL-2, 4, 6, 8, 10, 17, IFN-γ and TNF-α) in the peripheral blood plasma of aAA patients was performed at the baseline using cytometric bead analysis. The cytokine levels were compared with HC and correlated with response to immunosuppressive therapy (IST) at 3-months.

Results

The median age of cases was 29 years (range,13–74). The cases had higher mean levels of IL2 (p = 0.326), IL4 (p = 0.038), IL6 (p = 0.000), IL10 (p = 0.002), TNF-α (p = 0.302), IFN-γ (p = 0.569) and IL-17 (p = 0.284) than the HC. The baseline levels of all the cytokines were higher (statistically non-significant) among responders (n = 13) than the non-responders (n = 14) to IST.

Conclusions

Baseline cytokine profile in patients with aAA might predict response to the IST. Larger studies are needed to validate our results.

Immune thrombocytopenia (ITP) is an autoimmune disease caused by the loss of immune tolerance to platelet autoantigens, resulting in reduced platelet production and increased platelet destruction. Impaired megakaryocyte differentiation and maturation is a key factor in the pathogenesis and treatment of ITP. Sarcandra glabra, a plant of the Chloranthaceae family, is commonly used in clinical practice to treat ITP, and daucosterol (Dau) is one of its active ingredients. However, whether Dau can treat ITP and the key mechanism of its effect are still unclear. In this study, we found that Dau could effectively promote the differentiation and maturation of megakaryocytes and the formation of polyploidy in the megakaryocyte differentiation disorder model constructed by co-culturing Dami and HS-5 cells. In vivo experiments showed that Dau could not only increase the number of polyploidized megakaryocytes in the ITP rat model, but also promote the recovery of platelet count. In addition, through network pharmacology analysis, we speculated that the JAK2-STAT3 signaling pathway might be involved in the process of Dau promoting megakaryocyte differentiation. Western blot results showed that Dau inhibited the expression of P-JAK2 and P-STAT3. In summary, these results provide a basis for further studying the pharmacological mechanism of Dau in treating ITP.

Background

Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow–derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes.

Methods

Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells. Cytoscape software was used to predict the circRNA-miRNA-mRNA networks, and their expression at the cellular level was detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). qRT-PCR was utilized to detect the expression levels of circ_0014614，miR-138-5p and caspase3 mRNA. Western blot was used to determine the protein levels of GATA-1, RUNX-1, NF-E2, CD41 and caspase3. The proliferation of K562 cells was assessed using the Cell Counting Kit-8 (CCK-8) Assay. Furthermore, the interplay between miR-138-5p and circ_0014614 or caspase3 was elucidated through a Dual-luciferase reporter assay.

Results

FISH assay indicated circ_0014614's primary cytoplasmic location in K562 cells. In ET bone marrow and K562 cells, circ_0014614 and caspase3 were down-regulated, whereas miR-138-5p saw a significant surge. Overexpressing circ_0014614 curtailed K562 cells' proliferation and differentiation. Further, circ_0014614 targeted miR-138-5p, with heightened miR-138-5p levels counteracting circ_0014614's inhibition. MiR-138-5p further targeted caspase3, and caspase3 silencing neutralized suppressed miR-138-5p's effects on K562 cell differentiation.

Conclusion

Circ_0014614 was down-regulated in ET bone marrow and bone marrow lineage cells, and upregulating circ_0014614 can inhibit bone marrow lineage cells' proliferation and differentiation into megakaryocytes. Mechanistically, circ_0014614 functioned as ceRNA via sponging miR-138-5p and alleviated the inhibitory effect of miR-138-5p on its target caspase3, which potentially deters tumor activity in ET.

COVID-19 disease progression can be accompanied by a “cytokine storm” that leads to secondary sequelae such as acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 disease progression, but have high daily intra-individual variability. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (GPF) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. COVID-19 patients were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using a commercial ELISA. We found that COVID-19 patients can develop extraordinarily high levels of GPF. Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients.

Sickle cell disease (SCD) is an hemoglobinopathy resulting in the production of an abnormal Hb (HbS) which can polymerize in deoxygenated conditions, leading to the sickling of red blood cells (RBC). These alterations can decrease the oxygen-carrying capacity leading to impaired function and energetics of skeletal muscle. Any strategy which could reverse the corresponding defects could be of interest. In SCD, endurance training is known to improve multiples muscle properties which restores patient's exercise capacity but present reduced effects in anemic patients. Hydroxyurea (HU) can increase fetal hemoglobin production which can reduce anemia in patients. The present study was conducted to determine whether HU can improve the effects of endurance training to improve muscle function and energetics. Twenty SCD Townes mice have been trained for 8 weeks with (n = 11) or without (n = 9) HU. SCD mice muscle function and energetics were analyzed during a standardized rest-exercise-recovery protocol, using Phosphorus-31 Magnetic resonance spectroscopy (³¹P-MRS) and transcutaneous stimulation. The combination of training and HU specifically decreased fatigue index and PCr consumption while muscle oxidative capacity was improved. These results illustrate the potential synergistic effects of endurance training and HU on muscle function and energetics in sickle cell disease.