Iron overload as a risk factor for poor graft function following allogeneic hematopoietic stem cell transplantation.

Hematological malignancies are increasingly treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, iron overload is a frequent adverse effect of allo-HSCT and is associated with poor prognosis. In the present study, we investigated hematopoiesis in iron-overloaded mice and elucidated the effects of iron overload on the bone marrow (BM) microenvironment. Iron-overloaded BALB/C mice were generated by injecting 20 mg/mL saccharated iron oxide intraperitoneally. Hematoxylin-eosin staining was performed to evaluate the effects of an iron overload in mice. BM cells obtained from C57BL/6 mice were transplanted into irradiated BALB/C mice (whole-body irradiation of 4 Gy, twice with a 4-hours interval) by tail vein injection. Two weeks after allo-HSCT, the hematopoietic reconstitution capacity was evaluated in recipients by colony-forming assays. Histopathological examinations showed brown-stained granular deposits, irregularly arranged lymphocytes in the liver tissues, and blue-stained blocks in the BM collected from mice received injections of high-dose saccharated iron oxide (20 mg/mL). Iron-overloaded mice showed more platelets, higher-hemoglobin (HGB) concentration, fewer granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte colony-forming units (CFU-E), and mixed granulocyte/erythrocyte/monocyte/megakaryocyte colony-forming units (CFU-mix) than healthy mice. Iron-overloaded recipients presented with reduced erythrocytes and HGB concentration in peripheral blood, along with decreased marrow stroma cells, CFU-GM, CFU-E, and CFU-mix relative to healthy recipients. Taken together, our findings demonstrate that iron overload might alter the number of red blood cells after transplantation in mice by destroying the BM microenvironment, thereby affecting the recovery of BM hematopoietic function.

Discovery of TAS2R14 Agonists from Platycodon grandiflorum Using Virtual Screening and Affinity Screening Based on a Novel TAS2R14-Functionalized HEMT Sensor Combined with UPLC-MS Analysis.

TAS2R14 is of great potential as a therapeutic target against asthma, and the discovery of TAS2R14 agonists can be very valuable for treating this disease. Herein, we developed a strategy using virtual screening and affinity screening based on a fabricated biosensor combined with UPLC-MS analysis to screen TAS2R14 agonists from Platycodon grandiflorum. By ligand-based virtual screening, 16 best-fit candidates were yielded. A novel TAS2R14-functionalized high-electron-mobility transistor (HEMT) sensor was applied to detect and fish out the potential TAS2R14 agonists from P. grandiflorum extracts. Those components captured by the immobilized TAS2R14 were eluted and characterized on UPLC-QTOF MS. As a result, six potential TAS2R14 agonists were screened out and identified. Among them, platycodin L was confirmed to be a special agonist of TAS2R14 for the first time and had an EC50 of 15.03 ± 1.15 µM via intracellular calcium mobilization assay ( n = 6). The results indicated that the proposed strategy was efficient to discover TAS2R14 agonists from the herb directly.