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Summary: Objective: Type 2 diabetes mellitus (T2DM) is a complex polygenic disease that causes hyperglycemia and accounts for 90%‐95% of all diabetes mellitus cases. Hence, this study aimed to examine the effects of microRNA‐219 (miR‐219) on inhibition of long‐term potentiation (LTP) and apoptosis of hippocampal neuronal cells in T2DM mice through the N‐methyl‐d‐aspartate receptor (NMDAR) signaling pathway regulation. Methods: The T2DM mouse models were established, after which LTP in vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured. Next, the density of pyramidal neurons in each group was calculated. Additionally, the expression levels of miR‐219, the NMDAR signaling pathway [NMDAR1 (NR) 1, NR2A, and NR2B), downstream target proteins [calmodulin‐dependent protein kinase‐II (CaMK‐II) and cAMP response element binding protein (CREB)], and apoptosis‐related factors [Bcl2‐associated X protein (Bax), c‐caspase‐9 and c‐caspase‐3] in the hippocampal tissues were determined. Finally, immunohistochemistry was applied to detect and measure the positive expression of Bax, caspase‐9, and caspase‐3 proteins. Results: The results showed that upregulation of miR‐219 increases LTP and density of pyramidal neurons in the hippocampal tissues of mice, while it decreases blood glucose of db/db mice. In addition, miR‐219 upregulation also leads to decreased mRNA levels of NR1, NR2A, NR2B, CaMK‐II, and CREB and protein levels of NR1, NR2A, NR2B, CaMK‐II, CREB, p‐CREB, Bax, c‐caspase‐9, and c‐caspase‐3. Furthermore, upregulation of miR‐219 inhibits positive expression of Bax, caspase‐9, and caspase‐3 proteins, leading to the suppression of hippocampal neuronal cell apoptosis. Conclusion: The findings from this study indicated that the upregulation of miR‐219 decreases LTP inhibition and hippocampal neuronal cell apoptosis in T2DM mice by downregulating the NMDAR signaling pathway, therefore suggesting that MiR‐219 might be a future therapeutic strategy for T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Background: Childhood acute lymphoblastic leukemia (ALL), a heterogeneous disease that includes multiple subtypes is defined by cell lineage and chromosome anomalies. Previous genome-wide association studies have reported several ARID5B and IKZF1 single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. High-resolution melting (HRM) analysis is a rapid and convenient technique to detect SNPs; we thereby detected SNPs in ARID5B and IKZF1 genes. Methods: We enrolled 79 pediatric ALL patients and 80 healthy controls. Polymorphic variants of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs7073837, rs10740055, and rs7089424) were detected by HRM, and SNPs were analyzed for association with childhood ALL. Results: The distribution of genotype rs7073837 in ARID5B significantly differed between ALL and controls (P =0.046), while those of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs10740055 and rs7089424) did not. We analyzed the association for SNPs with B lineage ALL to find rs7073837 in ARID5B, conferring a higher risk for B lineage ALL (odds ratio, OR=1.70, 95% confidence interval, CI=1.01–2.87, P =0.049). Conclusion: HRM is a practical method to detect SNPs in ARID5B and IKZF1 genes. We found that rs7073837 in ARID5B correlated with a risk for childhood B lineage ALL. [Copyright &y& Elsevier]

Abstract: The FLT3 gene with internal tandem duplication (ITD) is a poor prognostic factor in patients with acute myeloid leukemia (AML), and the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for AML patients with FLT3-ITD is controversial. We examined 122 AML patients; 34 patients had FLT3-ITD and 39 patients received allogeneic HSCT. The median overall survival (OS) of patients with wtFLT3/nonHSCT, wtFLT3/HSCT, FLT3-ITD/nonHSCT and FLT3-ITD/HSCT was 40.7 months, 53.4 months, 9.8 months and not reached, respectively (p =0.006). Compared to the wtFLT3/nonHSCT patients, the hazard ratio (95% CI) of OS for wtFLT3/HSCT, FLT3-ITD/nonHSCT and FLT3-ITD/HSCT was 1.39 (0.61–3.18), 3.57 (1.58–8.10) and 0.40 (0.11–1.59), respectively, after adjustment of age, sex, WBC, LDH, karyotype, NPM, and FAB classification. This result indicated that patients with FLT3-ITD/nonHSCT had a significantly worse outcome, but allogeneic HSCT improved the prognosis for patients with FLT3-ITD. [Copyright &y& Elsevier]