The prognosis of chemoresistant acute myeloid leukemia (AML) is still poor, mainly owing to the sustained proliferation ability of leukemic cells, while the microtubules have a major role in sustaining the continuity of cell cycle. In the present study, we have identified CENPE, a microtubular kinesin-like motor protein that is highly expressed in the peripheral blood of patients with chemoresistant AML. In our in vitro studies, knockdown of CENPE expression resulted in the suppression of proliferation of myeloid leukemia cells and reversal of cytarabine (Ara-C) chemoresistance. Furthermore, Lin28A, one of the RNA-binding oncogene proteins that increase cell proliferation and invasion and contribute to unfavorable treatment responses in certain malignancies, was found to be remarkably correlated with CENPE expression in chemoresistance AML. Overexpression of LIN28A promoted the proliferation and Ara-C chemoresistance of leukemic cells. RIP assay, RNA pull-down, and dual luciferase reporter analyses indicated that LIN28A bound specifically to the promoter region GGAGA of CENPE. In addition, the impacts of LIN28A on cell growth, apoptosis, cell cycle progression, and Ara-C chemoresistance were reverted by the knockdown of CENPE. Hence, Lin28A/CENPE has enhanced the proliferation and chemoresistance of AML, and therefore, it could be a prospective candidate for AML treatment.

Macrophages play an important role in the pathogenesis of systemic lupus erythematosus–associated diffuse alveolar hemorrhage (DAH). The immunomodulation of macrophage responses might be a potential approach for the prevention and treatment of DAH. Erythropoietin (EPO) could regulate macrophage bioactivities by binding to the EPO receptor expressing on macrophages. This study assessed the effects of EPO on DAH protection using an immune-mediated DAH murine model with macrophages as the major contributor. A DAH murine model was established in female C57BL/6 mice by an i.p. injection of pristane. We found that EPO administration alleviates DAH by reducing pulmonary macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. EPO drove macrophages to the anti-inflammatory phenotype in the primary murine bone marrow–derived macrophages and macrophages cell line RAW 264.7 with LPS, IFN-γ, and IL-4 in vitro. Moreover, EPO treatment increases the expression of EPOR and decreases the expression of miR-494-3p, resulting in increased phosphorylation of JAK2 and STAT3. In conclusion, EPO can be a potential therapeutic agent in DAH by reducing cell apoptosis and regulating macrophage polarization through the EPOR/JAK2/STAT3 axis. Further studies are also needed to validate the direct target of miR-494-3p in regulating JAK2/STAT3 signaling transduction.

Objectives: There are significant differences in the composition of intestinal flora in renal transplant recipients before and after an operation, which has a great impact on the prognosis of renal transplantation. The purpose of this project is to study the effect of intestinal flora imbalance on renal transplantation.Methods: The animal model of renal transplantation was established after intestinal flora imbalance (mice pretreated with compound antibiotics), or the animal model of renal transplantation was established after being pretreated with single antibiotics. HE, PAS, and Masson staining was used to detecting the histopathological changes of transplanted renal. The expression of inflammatory factors and infiltration of inflammatory cells of renal tissue were respectively been detected by ELISA kit and flow cytometry.Results: Antibiotic pretreatment restored weight loss, and decreased serum creatinine level in mice after renal transplantation. The tissue staining, ELISA assay, and flow cytometry data showed that antibiotic pretreatment alleviated injury of the renal allograft, inhibited the inflammatory factors levels, and reduced inflammatory cell infiltration in mice after renal transplantation. Furthermore, single antibiotic, especially ampicillin pretreatment can also play the same role as compound antibiotics, such as restoring weight loss, decreasing serum creatinine level, alleviating renal allograft injury, inhibiting inflammatory factors levels, and reducing inflammatory cell infiltration in mice after renal transplantation.Conclusions: Antibiotic ampicillin may inhibit inflammatory cell infiltration after renal transplantation by regulating the proportion of intestinal flora in mice, to reduce renal injury and play a role in renal protection.