ERRα regulates synaptic transmission through reactive oxygen species in hippocampal neurons.

Reactive oxygen species (ROS) play multiple roles in synaptic transmission, and estrogen-related receptor α (ERRα) is involved in regulating ROS production. The purpose of our study was to explore the underlying effect of ERRα on ROS production, neurite formation and synaptic transmission. Our results revealed that knocking down ERRα expression affected the formation of neuronal neurites and dendritic spines, which are the basic structures of synaptic transmission and play important roles in learning, memory and neuronal plasticity; moreover, the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were decreased. These abnormalities were reversed by overexpression of human ERRα. Additionally, we also found that knocking down ERRα expression increased intracellular ROS levels in neurons. ROS inhibitor PBN rescued the changes in neurite formation and synaptic transmission induced by ERRα knockdown. These results indicate a new possible cellular mechanism by which ERRα affects intracellular ROS levels, which in turn regulate neurite and dendritic spine formation and synaptic transmission.

[The Relationship between Speed of Platelet Recovery and Its R-squared and Efficacy after First Induction Chemotherapy in Acute Myeloid Leukemia].

OBJECTIVE: To calculate the cut-off values of speed of platelet recovery and its R-squared in patients with acute myeloid leukemia (AML) after initial induction chemotherapy, which were used to predict the complete remission (CR) of the first induction chemotherapy, and guide the clinic to choose the next appropriate chemotherapy regimen as soon as possible. METHODS: A total of 117 patients with newly diagnosed AML in the Second Hospital of Shanxi Medical University were included. Patients were diagnosed by morphology, immunology, cytogenetics, and molecular biology (MICM) classification, and the risk stratification was evaluated in combination with the clinical situations of the patients at the time of admission. The peripheral platelet counts after the first induction chemotherapy were detected and the linear regression equation was used to calculate the recovery speed of platelet counts in 5 consecutive blood cell analysis before discharge. According to the ROC curve, the cut-off value between the recovery speed and the R-squared was calculated, and the cut-off value was used to divide the patients into different groups. The differences between groups were compared by Pearson χ2 test to observe the remission effect of the first induction chemotherapy. RESULTS: ROC curve analysis showed that the cut-off value for predicting the platelet recovery speed and its R-squared of the first induction chemotherapy to achieve remission was 4.059 5×109/(L·d) and 72.7%, the sensitivity was 77% and 63.9%, the specificity was 62.5% and 67.9%, and the Youden index was 0.395 and 0.318, respectively. The patients were divided into different groups and compared according to the above cut-off values, and the results showed statistical differences (P<0.001, P=0.001). CONCLUSION: The cut-off value of platelet recovery speed and its R-squared after the first induction chemotherapy calculated by peripheral platelet count and ROC curve in AML patients can be used as an index to evaluate the remission. The faster the platelet recovery speed after chemotherapy is, the more likely patients achieve remission. The more stable the platelet recovery tendency is, the more likely patients achieve remission too.

Epigenetic Targets and their Inhibitors in Cancer Therapy.

Epigenetics is defined as the stable and heritable alternations in gene expression without changing the DNA nucleotide sequence. The initiation and progression of cancer result from not only genetic mutation, but also aberrant epigenetic regulation, such as DNA methylation and histones acetylation. Although Genetic alternations cannot be reversed, epigenetic modification is a dynamic and reversible process. Over the past few decades, much progress has been made in the research of epigenetic medications and a variety of drugs have been developed targeting at epigenetic regulatory proteins, which are capable of restoring malignant cancer cells to the normal state. The epigenetic drugs currently approved for cancer treatment mainly target at DNA methylation and histones acetylation. In addition, there are a great many epigenetic drugs in clinical trials for cancer therapy, such as inhibitors of DNA methyltransferases, histone deacetylases, histone methyltransferases, lysine specific demethylases, and BET (bromodomain and extra-terminal domain) family proteins. We will discuss the latest developments of these inhibitors and their applications in cancer therapy.