No abstract

The novel selective BCR-ABL Breakpoint cluster region – Abelson murine leukemia viral oncogene homolog 1 (BCR-AML) inhibitor nilotinib (AMN107) is a tyrosine kinase inhibitor that is more potent against leukaemia cells in vitro than imatinib. As nilotinib might be used in the context of allogeneic stem cell transplantation where CD8+ T lymphocytes play a pivotal role in the graft-versus-leukaemia (GVL) effect, we investigated effects of nilotinib on this lymphocyte subpopulation. Nilotinib inhibits phytohemagglutinin (PHA)-induced proliferation of CD8+T lymphocytes in vitro at therapeutically relevant concentrations (0.5–4 μM). The inhibition of CD8+ T lymphocytes specific for leukaemia or viral antigens through nilotinib was associated with a reduced expansion of antigen peptide specific CD8+ T lymphocytes and with a decreased release of interferon—γ and granzyme B by these cells as analysed by flow cytometry and enzyme-linked immunospot (ELISPOT) assays. The inhibitory effect caused by nilotinib was two times stronger than by imatinib. These effects were mediated through the inhibition of the phosphorylation of ZAP-70, Lck and ERK 1/2 and the NF-κβ signalling transduction pathway. Taken together, we observed a strong suppressive impact of nilotinib on the CD8+ T lymphocyte function which should be considered carefully in the framework of allogeneic stem cell transplantation or other T cell based immunotherapies.

This meta-analysis confirms the health hazards of heavy drinking (≥50 g/day) and benefits of light drinking (≤12.5 g/day). Large-sample, well-designed, prospective epidemiological studies, especially on heavy drinking among women, should be developed in future.

The intrinsically hole-doped RbEuFe4As4 exhibits bulk superconductivity at Tsc = 36.5 K and ferromagnetic ordering in the Eu sublattice at Tm = 15 K. Here we present a hole-compensation study by introducing extra itinerant electrons via a Ni substitution in the ferromagnetic superconductor RbEuFe4As4 with Tsc > Tm. With the Ni doping, Tsc decreases rapidly, and the Euspin ferromagnetism and its Tm remain unchanged. Consequently, the system RbEu(Fe1−xNix)4As4 transforms into a superconducting ferromagnet with Tm > Tsc for 0.07 ≤ x ≤ 0.08. The occurrence of superconducting ferromagnets is attributed to the decoupling between Eu 2+ spins and superconducting Cooper pairs. The superconducting and magnetic phase diagram is established, which additionally includes a recovered yet suppressed spin-density-wave state.

mircoRNAs (miRNAs) play important roles on regulation of gene expressions. Aberrant expression of miRNAs was involved in various biological and pathological processes, including tumorigenesis of breast cancer. Single-nucleotide polymorphisms (SNPs) were implicated in altered expression or biological functions of mature miRNAs. To explore the relevance of miRNA polymorphisms and female physiological characteristics to breast cancer risk, SNPs located within hsa-miR-605 (rs2043556), hsa-miR-149 (rs2292832), hsa-miR-27a (rs895819), hsa-miR-196a-2 (rs11614913) and hsa-miR-618 (rs2682818) were selected, and their associations with breast cancer risk were analysed. In addition, associations between physiological characteristics-related factors and breast cancer risk were estimated too. We found that the ones with menarche age less than 16 years had increased breast cancer risk (OR = 2.10, 95% CI: 1.23-3.60). Marginally significant association between rs11614913 CT/CC genotypes and reduced breast cancer risk was observed (OR = 0.65, 95% CI: 0.40-1.06), while no significance was detected about the other miRNA polymorphisms. We concluded that menarche at less than 16 years old increased breast cancer risk, while the genetic variants in miR-196-a-2 might decrease the risk.