Influence of substrates on the <i>in vitro</i> kinetics of steviol glucuronidation and interaction between steviol glycosides metabolites and UGT2B7

<p>Steviol glycosides, a natural sweetener, may perform bioactivities via steviol, their main metabolite in human digestion. The metabolising kinetics, i.e. glucuronidation kinetics and interaction between steviol glycosides or their metabolites and metabolising enzyme, are important for understanding the bioactivity and cytotoxicity. The present study investigated kinetics of steviol glucuronidation in human liver microsome and a recombinant human UDP-glucuronosyltransferases isomer, UGT2B7, along with molecular docking to analyse interaction between UGT2B7 and steviol or glucose. The active pocket of UGT2B7 is consisted of Arg352, Leu347, Lys343, Phe339, Tyr354, Lys355 and Leu353. The influence of stevioside, rebaudioside A, glucose and some chemotherapy reagents on the glucuronidation was also studied. The predicted hepatic clearence suggested that steviol could be classified as high-clearence drug. The steviol glycosides did not affect the glucuronidation of steviol notably.</p

Additional file 1: Figure S1. of Pyrosequencing quantified methylation level of miR-124 predicts shorter survival for patients with myelodysplastic syndrome

Quantitative DNA methylation of miR-1241-1, miR-124-2 and miR-124-3 in 56 MDS patients and peripheral blood from 10 healthy donors. Each row represents a sample, and each column represents a single CG site. Colour coding reflects the degree of methylation with yellow being 100% and blue being 0%. Figure S2. After transfection with miR-124 mimics (a) and miR-124 inhibitors (b) in SKM-1 cells, miR-124 expression was determined by real-time PCR and normalized to U6. (PDF 55 kb

DataSheet_1_Case Report: Blinatumomab therapy for the treatment of B-cell acute lymphoblastic leukemia patients with central nervous system infiltration.docx

The treatment of B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement poses a significant clinical challenge because most chemotherapeutic agents exhibit weak permeability to the blood-brain barrier (BBB). In addition, current anti-CNS leukemia treatments often bring short or long-term complications. Immunotherapy including chimeric antigen T-cell therapy and bispecific antibody have shown profound treatment responses in relapsed/refractory B-ALL. However, there is a lack of data on the efficacy of bispecific antibody in treating B-ALL with CNS involvement. Here, we report two ALL patients with CNS leukemia who received blinatumomab. Case 1 was diagnosed with chronic myeloid leukemia in lymphoid blast phase. The patient developed CNS leukemia and bone marrow relapse during the treatment with dasatinib. Case 2 was diagnosed with B-ALL and suffered early hematologic relapse and cerebral parenchyma involvement. After treatment with one cycle of blinatumomab, both patients achieved complete remission in the bone marrow and CNS. Furthermore, this is the first report on the efficacy of blinatumomab in treating CNS leukemia with both of the cerebral spinal fluid and the cerebral parenchymal involvement. Our results suggest that blinatumomab might be a potential option for the treatment of CNS leukemia.</p