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The dysregulation of beta-catenin, a key regulator of cadherin-mediated cell adhesion and crucial for embryonic development and adult tissue processes, has been implicated in various cancers, including colon cancer. Meanwhile, there have been longstanding concerns about the potential carcinogenic effects of magnetic fields. In this study, we investigated the possible relationship between beta-catenin dysfunction and 50 Hz sinusoidal magnetic fields (SMF) using an animal model of N-methyl-N-nitrosourea (MNU)-induced rat colon tumors. To assess beta-catenin phosphorylation, genomic DNA was extracted from 58 samples using a commercial extraction kit, and the target gene region corresponding to an important phosphorylation site of beta-catenin was amplified via polymerase chain reaction (PCR). The amplified samples were subsequently analyzed using the single-strand conformation polymorphism (SSCP) method to detect any differences between the experimental groups. Surprisingly, our results revealed no significant differences in beta-catenin gene phosphorylation sites among the groups. These findings suggest that 50 Hz SMF exposure may not directly impact betacatenin dysfunction in the context of MNU-induced rat colon tumors. Implications of these results and avenues for further research are discussed. [ABSTRACT FROM AUTHOR]

Background: Coagulation factors, anticoagulants, and fibrinolytic proteins are important for hemostasis, and mutations affecting these proteins causes some rare inherited bleeding disorders that are particularly challenging to diagnose. Aims: This review provides current information on rare inherited bleeding disorders that are difficult to diagnose. Material & Methods: A review of the literature was conducted for up to date information on rare and difficult to diagnose bleeding disorders. Results: Some rare bleeding disorders cause an inherited deficiency of multiple coagulation factors (F), such as combined FV and FVIII deficiency and familial vitamin K‐dependent clotting factor deficiency. Additionally, congenital disorders of glycosylation can affect a variety of procoagulant and anticoagulant proteins and also platelets. Some bleeding disorders reflect mutations with unique impairments in the procoagulant/anticoagulant balance, including those caused by F5 mutations that secondarily increase the plasma levels of tissue factor pathway inhibitor as well as THBD mutations that increase functional thrombomodulin in plasma or cause a consumptive coagulopathy due to thrombomodulin deficiency. Some bleeding disorders accelerate fibrinolysis due to loss‐of‐function mutations in SERPINE1 and SERPINF2 or in the case of Quebec platelet disorder, a duplication mutation that rewires PLAU and selectively increases expression in megakaryocytes, resulting in a unique platelet‐dependent gain‐of‐function defect in fibrinolysis. Discussion: Current information on rare and difficult to diagnose bleeding disorders indicates they have unique clinical and laboratory features, and pathogenic characteristics to consider for diagnostic evaluation. Conclusion: Laboratories and clinicians should consider rare inherited disorders, and difficult to diagnose conditions, in their strategy for diagnosing bleeding disorders. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia is characterized by abnormal differentiation of hematopoietic stem cells, leading to the accumulation of immature myeloid cells. Differentiation therapy has been a successful treatment option for acute promyelocytic leukemia but suffers from adverse effects. Therefore, search for novel differentiation-inducing agents with minimal side effects is desirable. Securinine, a naturally-occurring alkaloid, induces differentiation in various leukemic cells and apoptosis in other types of cancers. However, the underlying molecular mechanism(s) remain elusive. Our study aimed to elucidate the possible molecular mechanism(s) and signaling events involved in securinine-induced differentiation of HL-60 cells. Securinine inhibited proliferation in a time- and dose-dependent manner and triggered differentiation. A higher CD14+ population indicated maturation toward monocytic lineage. Securinine caused cell cycle arrest at the G0/G1 phase and enhanced ROS generation. Quantitative gene expression analysis showed significant down-regulation of C/EBP-α, C/EBP-ε, GAΤΑ, and c-myc and up-regulation of the PU.1 gene. The expression of distinct protein kinases Lyn, Chk-2, Yes, FAK, c-Jun, and JNK were enhanced. Use of specific inhibitors of crucial intracellular signaling proteins indicated that JNK and ERK blockade resulted in a significant decline in differentiation. These data thus confirm that securinine induces differentiation through the activation of the JNK-ERK signaling pathway in HL-60 cells. [ABSTRACT FROM AUTHOR]