Turkish Journal of Hematology最新文献

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare chronic bone marrow failure condition characterized by complement-mediated hemolytic anemia and thrombosis. While its initial clinical description occurred in 1882, somatic mutations in PIGA were discovered in the 1990s. With an improved understanding of PNH biology, a focused effort on complement inhibitors led to the discovery of eculizumab, a C5 inhibitor initially approved by the US Food and Drug Administration in 2007. Terminal complement pathway inhibition reduced intravascular hemolysis, anemia, and thrombosis. Further advancements in drug development for PNH have included improved pharmacokinetics with ravulizumab in 2018 and the introduction of proximal complement inhibitors such as pegcetacoplan (2021), iptacopan (2023), danicopan (2024), and crovalimab (2024) to enhance patient outcomes. With these new proximal and distal complement inhibitors in the treatment landscape, it is timely for clinicians to review the evolving landscape of PNH treatments and patient selection.

Objective: This study comprehensively compares the efficacy, safety, and tolerability of two commonly used intravenous iron preparations, ferric carboxymaltose (FCM) and iron sucrose (IS), in adult patients with iron-deficiency anemia (IDA).

Materials and methods: A systematic literature search was conducted across the PubMed, Ovid MEDLINE, Web of Science, and Cochrane Library databases up to January 1, 2024, to identify randomized controlled trials directly comparing FCM and IS treatments in adult patients with IDA. The primary outcome of interest was change in hemoglobin (Hb) levels during follow-up. Meta-analyses were conducted with inverse variance random effects models.

Results: Fourteen trials were included in the study, with a total of 4757 patients. FCM resulted in a non-significant increase in Hb levels (mean difference [MD]: 0.45 g/dL, 95% confidence interval [CI]: 0.08 to 0.83, p=0.02) and ferritin levels (MD: 37.32 ng/mL, 95% CI: 18.98 to 55.65, p<0.01) compared to IS. FCM was associated with a higher risk of hypersensitivity reactions compared to IS (relative risk [RR]: 2.97, 95% CI: 1.35 to 6.52, p<0.01) but showed no significant difference in severe adverse events (RR: 1.03, 95% CI: 0.88 to 1.21, p=0.70) and had a non-significant increased risk of hypophosphatemia (RR: 2.84, 95% CI: 0.89 to 9.06, p=0.08).

Conclusion: Ten studies showed some concerns of risk of bias (RoB) and four studies had a high RoB for the change in Hb levels during follow-up. The lack of standardized definitions for hypersensitivity reactions and variability in dosing protocols and follow-up durations across studies may affect the generalizability of our safety findings.

Objective: Deep vein thrombosis (DVT) is a vascular disorder with an incidence rate of about 0.1%. Endothelial progenitor cells (EPCs) are precursor cells of endothelial cells and contribute to vascular repair and regeneration. Circular RNA (circRNA) has become a new focus of research as circRNAs are involved in various biological processes including the progression of DVT. This study explored the upregulation of hsa_circRNA_092488 in DVT patients.

Materials and methods: The expression of hsa_circRNA_092488 was evaluated in venous blood samples obtained from DVT patients (n=42) and healthy controls (n=42). Gain- and loss-of-function studies of hsa_circRNA_092488 were carried out. The expression levels of related RNAs and proteins were examined by quantitative real-time reverse-transcription polymerase chain reaction, western blotting and immunofluorescence assays. The proliferation, migration, cell cycle progression, and apoptosis of transfected cells were measured by CCK-8 assay, transwell assay, and flow cytometry. The association of hsa_circRNA_092488 and NOD-like receptor protein 3 (NLRP3) in EPCs was revealed using RNA pull-down analysis. Furthermore, the stability of NLRP3 mRNA was examined in transfected EPCs.

Results: Upregulation of hsa_circRNA_092488 was detected in blood samples from DVT patients and it had the ability to suppress the proliferation and migration of EPCs, induce cell cycle arrest from the S to the G0/G1 phase, and trigger cellular apoptosis. Furthermore, NLRP3 was identified as the potential downstream target molecule of hsa_circRNA_092488 and it could exert its regulatory functions by activating the NLRP3/nuclear factor (NF)-κB signaling pathway. Overexpression of hsa_circRNA_092488 in cells notably elevated the protein expression of caspase-1, interleukin-1β, P-NF-κB-p65/NF-κB-p65, and P-IκBα/IκBα, while knockdown of hsa_circRNA_092488 significantly reduced the levels of those proteins in EPCs.

Conclusion: hsa_circRNA_092488/NLRP3/NF-κB signaling could be a novel therapeutic candidate for the treatment of DVT.